ECT For Schizophrenia

Electroconvulsive therapy for schizophrenia (Review)
Tharyan P, Adams CE
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2005, Issue 2 http://www.thecochranelibrary.com
Electroconvulsive therapy for schizophrenia (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 1 Global impression: 1a. Not improved. Analysis 1.2. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 2 Global impression: 2. Not discharged from hospital. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 3 Global impression: 3. Relapse. . . Analysis 1.4. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 4 Global impression: 4. Average endpoint score (MHS scale, high score=good). . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 5 Mental state: 1. Average endpoint score (BPRS, high score = poor). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.6. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 6 Mental state: 2. Average endpoint score medium term (Jenkin scale, high score = poor). . . . . . . . . . . . . . . . . . . . . . . Analysis 1.7. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 7 Behaviour: Average endpoint score medium term (MACC scale, high score = good). . . . . . . . . . . . . . . . . . . . . . . Analysis 1.8. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 8 Employment: 1. On ward. . . . Analysis 1.9. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 9 Leaving the study early. . . . . Analysis 1.10. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 10 Adverse effects: 1. Memory. . . Analysis 1.11. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 11 Adverse effects: 2. Other. . . . Analysis 1.12. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 12 Death - within three years after treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.1. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 1 Global impression: 1. Not improved - at end of course of ECT. . . . . Analysis 2.2. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 2 Global impression: 2. Relapse - short term (vs antipsychotics alone). . . Analysis 2.3. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 3 Global impression: 3. Not discharged from hospital (vs antipsychotics alone). Analysis 2.4. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 4 Global impression: 4. Average endpoint score (MHS, high = good). . . Analysis 2.5. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 5 Mental state: 1. Average endpoint score (BPRS, high score = poor). . . Analysis 2.6. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 6 Mental state: 2. Average endpoint score (Jenkin scale, high = poor). . . Analysis 2.7. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 7 Behaviour: Average endpoint score - medium term (MACC, high = good). Analysis 2.8. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 8 Leaving the study early. . . . . . . . . . . . . . . . . . Analysis 2.9. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 9 Adverse effects: 1. Memory - vs antispychotics and sham ECT. . . . . Analysis 2.10. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 10 Adverse effects: 2. Memory - vs antipsychotics. . . . . . . .
1 1 2 2 5 5 8 17 21 22 22 33 62 70 71 72 73 74 75 75 76 77 78 79 79 80 81 81 82 83 84 85 86 87 88
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Analysis 2.11. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 11 Adverse effects: 3. Extrapyramidal side effects - vs antipsychotics and sham ECT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.12. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 12 Adverse effects: 4. Extrapyramidal side effects - vs antipsychotics. . Analysis 2.13. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 13 Adverse effects: 5. Other - vs antipsychotics and sham ECT. . . . Analysis 2.14. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 14 Adverse events: 6. Other - vs antipsychotics. . . . . . . . . Analysis 2.15. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 15 Death within three years of treatment - vs antipsychotics. . . . Analysis 3.1. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 1 Global impression: 1. Not improved - at end of course of ECT. . . . . . . . . . . . . . . . . . Analysis 3.2. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 2 Global impression: 2. Not discharged from hospital. . . . . . . . . . . . . . . . . . . . . Analysis 3.3. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 3 Global impression: 3. Average endpoint score (MHS, high score = good). . . . . . . . . . . . . . Analysis 3.4. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 4 Mental state: Average endpoint score - medium term (Jenkin scale, high = poor). . . . . . . . . . . . Analysis 3.5. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 5 Behaviour: Average endpoint score - medium term (MACC scale; high = good). . . . . . . . . . . . Analysis 3.6. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 6 Leaving the study early. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.7. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 7 Death - within three years after treatment. . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.1. Comparison 4 ECT versus INSULIN COMA THERAPY, Outcome 1 Global impression: Not improved - at end of course of ECT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.2. Comparison 4 ECT versus INSULIN COMA THERAPY, Outcome 2 Leaving the study early. . . . Analysis 4.3. Comparison 4 ECT versus INSULIN COMA THERAPY, Outcome 3 Relapse. . . . . . . . . Analysis 5.1. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 1 Global impression: 1. Average endpoint score (GAF, high scores = good). . . . . . . . . . . . . . . . . . . . . Analysis 5.2. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 2 Global impression: 2. Relapse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.3. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 3 Mental state: Average endpoint score ( BPRS, high scores = poor). . . . . . . . . . . . . . . . . . . . . Analysis 5.4. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 4 Leaving study early. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.5. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 5 Adverse effects cognitive: Average endpoint score (MMSE, high scores = good). . . . . . . . . . . . . . . . . Analysis 6.1. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 1 Global impression: 1. Not improved. . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.2. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 2 Mental state: 1. Average endpoint score (BPRS, high = poor). . . . . . . . . . . . . . . . . . Analysis 6.3. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 3 Adverse effects: 1. Memory - at end of course of ECT. . . . . . . . . . . . . . . . . . . . . Analysis 6.4. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 4 Adverse effects: 2. Memory - average end point score. . . . . . . . . . . . . . . . . . . . . Analysis 7.1. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 1 Global impression: not improved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.2. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 2 Leaving study early. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.3. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 3 SUBGROUP of people in remission - Number of ECT treatments: 1. To rst improvement. . . . . . . . . . . .
89 90 91 92 92 93 94 95 96 97 98 99 99 100 100 101 102 103 104 105 106 107 108 109 110 111 112
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Analysis 7.4. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 4 SUBGROUP of people in remission - Number ECT treatments: 2. At end of course of ECT. . . . . . . . . . . . Analysis 7.5. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 5 SUBGROUP of people in remission - Days of treatment: 1. To rst improvement. . . . . . . . . . . . . . . . Analysis 7.6. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 6 SUBGROUP of people in remission - Days of treatment: 2. At end of course of ECT. . . . . . . . . . . . . . . Analysis 8.1. Comparison 8 ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL), Outcome 1 Adverse effects: 1. Cognitve impairment clinically apparent. . . . . . . . . . . . . . . . . . . Analysis 8.2. Comparison 8 ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL), Outcome 2 Adverse effects: 2. Memory - Average endpoint score (Weshler memory scale-form I, high score = good). . . Analysis 9.1. Comparison 9 ECT - NUMBER OF TREATMENTS: 12 versus 20 TREATMENTS, Outcome 1 Global impression: Not improved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
113 114 115 116 116 117 117 120 120 120 121 121 121 121
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[Intervention Review]
Electroconvulsive therapy for schizophrenia

Prathap Tharyan1 , Clive E Adams2
1 South Asian Cochrane Network & Centre, Prof. BV Moses & ICMR Advanced Centre for Research & Training in Evidence Informed Health Care, Christian Medical College, Vellore, India. 2 Cochrane Schizophrenia Group, University of Nottingham, Nottingham, UK
Contact address: Prathap Tharyan, South Asian Cochrane Network & Centre, Prof. BV Moses & ICMR Advanced Centre for Research & Training in Evidence Informed Health Care, Christian Medical College, Carman Block II Floor, CMC Campus, Bagayam, Vellore, Tamil Nadu, 632002, India. prathap@cmcvellore.ac.in. cochrane@cmcvellore.ac.in. Editorial group: Cochrane Schizophrenia Group. Publication status and date: Edited (no change to conclusions), published in Issue 4, 2009. Review content assessed as up-to-date: 15 February 2005. Citation: Tharyan P, Adams CE. Electroconvulsive therapy for schizophrenia. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD000076. DOI: 10.1002/14651858.CD000076.pub2. Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background Electroconvulsive therapy (ECT) involves the induction of a seizure for therapeutic purposes by the administration of a variable frequency electrical stimulus shock via electrodes applied to the scalp. The effects of its use in people with schizophrenia are unclear. Objectives To determine whether electroconvulsive therapy (ECT) results in clinically meaningful benet with regard to global improvement, hospitalisation, changes in mental state, behaviour and functioning for people with schizophrenia, and to determine whether variations in the practical administration of ECT inuences outcome. Search methods We undertook electronic searches of Biological Abstracts (1982-1996), EMBASE (1980-1996), MEDLINE (1966-2004), PsycLIT (1974-1996),SCISEARCH (1996) and the Cochrane Schizophrenia Groups Register (July 2004). We also inspected the references of all identied studies and contacted relevant authors. Selection criteria We included all randomised controlled clinical trials that compared ECT with placebo, sham ECT, non-pharmacological interventions and antipsychotics and different schedules and methods of administration of ECT for people with schizophrenia, schizoaffective disorder or chronic mental disorder. Data collection and analysis Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% condence intervals (CI) with the number needed to treat (NNT). For continuous data Weighted Mean Differences (WMD) were calculated. We presented scale data for only those tools that had attained pre-specied levels of quality. We also undertook tests for heterogeneity and publication bias.
Electroconvulsive therapy for schizophrenia (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
Main results This review includes 26 trials with 50 reports. When ECT is compared with placebo or sham ECT, more people improved in the real ECT group (n=392, 10 RCTs, RR 0.76 random CI 0.59 to 0.98, NNT 6 CI 4 to 12) and though data were heterogeneous (chi-square 17.49 df=9 P=0.04), its impact on variability of data was not substantial (I-squared 48.5%). There was a suggestion that ECT resulted in less relapses in the short term than sham ECT (n=47, 2 RCTs, RR xed 0.26 CI 0.03 to 2.2), and a greater likelihood of being discharged from hospital (n=98, 1 RCT, RR xed 0.59, CI 0.34 to 1.01). There is no evidence that this early advantage for ECT is maintained over the medium to long term. People treated with ECT did not drop out of treatment earlier than those treated with sham ECT (n=495, 14 RCTs, RR xed 0.71 CI 0.33 to 1.52, I-squared 0%). Very limited data indicated that visual memory might decline after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI -23 to -5); the results of verbal memory tests were equivocal. When ECT is directly compared with antipsychotic drug treatments (total n=443, 10 RCTs) results favour the medication group (n= 175, 3 RCTs, RR xed not improved at the end of ECT course 2.18 CI 1.31 to 3.63). Limited evidence suggests that ECT combined with antipsychotic drugs results in greater improvement in mental state (n= 40, 1 RCT, WMD, Brief Psychiatric Rating Scale -3.9 CI - 2.28 to -5.52) than with antipsychotic drugs alone. One small study suggested more memory impairment after a course of ECT combined with antipsychotics than with antipsychotics alone (n=20, MD serial numbers and picture recall -4.90 CI -0.78 to -9.02), though this proved transient. When continuation ECT was added to antipsychotic drugs, the combination was superior to the use of antipsychotics alone (n=30, WMD Global Assessment of Functioning 19.06 CI 9.65 to 28.47), or CECT alone (n=30, WMD -20.30 CI -11.48 to -29.12). Unilateral and bilateral ECT were equally effective in terms of global improvement (n=78, 2 RCTs, RR xed not improved at end of course of ECT 0.79 CI 0.45 to 1.39). One trial showed a signicant advantage for 20 treatments over 12 treatments for numbers globally improved at the end of the ECT course (n=43, RR xed 2.53 CI 1.13 to 5.66). Authors conclusions The evidence in this review suggests that ECT, combined with treatment with antipsychotic drugs, may be considered an option for people with schizophrenia, particularly when rapid global improvement and reduction of symptoms is desired. This is also the case for those with schizophrenia who show limited response to medication alone. Even though this initial benecial effect may not last beyond the short term, there is no clear evidence to refute its use for people with schizophrenia. The research base for the use of ECT in people with schizophrenia continues to expand, but even after more than ve decades of clinical use, there remain many unanswered questions regarding its role in the management of people with schizophrenia.
PLAIN LANGUAGE SUMMARY Electroconvulsive therapy for schizophrenia The induction of a seizure (t) for therapeutic purposes by the administration of an electrical stimulus (electroconvulsive therapy or ECT) remains a common treatment option for people with schizophrenia. This review pools data from 26 studies that included over 798 participants in receipt of this treatment. The evidence suggests that courses of ECT can, in the short term, result in an increase in global improvement for some people with schizophrenia.
BACKGROUND
Electroconvulsive therapy (ECT) involves the induction of a seizure (t) for therapeutic purposes by the administration of a variable frequency electrical stimulus (shock) to the brain via electrodes applied to the scalp. The procedure is usually modied by
the use of short acting anaesthetics and muscle relaxants. The former reduces apprehension and the latter avoids unwanted adverse side events such as fractures of the spine or extremities due to the vigorous muscular convulsions that occur if a muscle relaxant is not used. In parts of the world where anaesthetics are not readily available, ECT is still administered without muscle relaxants and
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anaesthetic agents as unmodied or direct ECT (Andrade 1993). Modications in ECT practice over the last ve decades have considerably increased its safety (Sackeim 1991, Shapira 1991). Although concerns exist (Rose 2003), there is currently no conclusive evidence that ECT results in brain damage (Weiner 1986, Devanand 1994, Ende 2000). ECT is a treatment that has generated considerable controversy since its introduction in 1938. It predates the era of modern psychopharmacology (drug treatment) by more than a decade, and initially gained acceptance because of its perceived benets in the context of few alternatives and lack of emphasis on clinical trials (Khan 1993). Both the introduction of antipsychotics and antidepressants in the 1950s, and public and professional concerns that ECT is invasive and causes brain damage, resulted in a decline in its use. It was in fact subject to legal restrictions in parts of the world (Fink 1991). A series of well-conducted studies since the 1970s, have established the efcacy of ECT in the treatment of depressive disorders (Scott 1995, APA 2001, UK ECT Group 2003). It has been demonstrated that during the rst month of ECT, quality of life and function have improved along with cognitive behaviour and mood in those with depression (McCall 2004). Although initially introduced as a treatment for schizophrenia, the use of ECT for this condition is now not widespread in the developed world (Small 1985, Khan 1993) although in some developing areas it is still used for psychosis associated with childbirth. However, in many parts of the developing world, where ECT is available and inexpensive, schizophrenia continues to be an indication for the use of ECT (Agarwal 1992). For people with schizophrenia, antipsychotic drugs effectively treat symptoms such as delusions, hallucinations and reduce the rate of relapse (Schooler 1993). Twenty percent of people with schizophrenia, however, fail to respond to antipsychotics (Marder 1993). This fact, together with concern over the distressing and enduring adverse effects of antipsychotic medication, has revived interest in the use of ECT for schizophrenia (Devanand 1991, Lock 1995a). There is a marked lack of consensus among expert groups and clinicians regarding the efcacy of ECT when used for people with schizophrenia (Salzman 1980, Fink 1996, Johns 1995, Kruger 1995). The American Psychiatric Association Committee on Electroconvulsive Therapy, in its Task Force Report (APA 2001), recommends the use of ECT in people with schizophrenia in the following cases: psychotic exacerbations of an abrupt or recent onset; catatonic schizophrenia (a subtype of schizophrenia where the person becomes mute and stuporous often adopting bizarre postures, known as catatonic stupor, or demonstrates excessive activity (catatonic excitement); where a history of a favourable response to ECT is present or for treating related psychotic disorders such as schizophreniform disorder (where the symptoms of schizophrenia have been present for less than six months) and schizoaffective disorder (where there is a mixture of symptoms of schizophrenia and that of a mood disorder). The Royal College
of Psychiatrists Special Committee on ECT in its second report (Royal College 1995) also considers ECT to be effective in people with schizophrenia with positive, affective or catatonic symptoms. However, the National Institute for Clinical Excellence in the UK (NICE 2003) does not recommend the general use of ECT for people with schizophrenia, although catatonia (which may occur in depressive disorders as well) is considered an indication. Technical background Much of our current knowledge regarding efcacy comes from studies conducted over the last 30 years for people with depressive disorders. These studies have demonstrated that, apart from clinical and diagnostic issues, variations in the practical administration of ECT impact substantially on the rate and extent of improvement, as well as on the unwanted cognitive adverse effects (confusion, memory impairment). These variations include: the type of ECT machine and stimulus wave form used; the degree to which the stimulus intensity exceeds the threshold at which seizures are elicited; the duration of seizures; bilateral versus unilateral placement of stimulus electrodes; the frequency and duration of prior resistance to antidepressant drugs and continuation treatment with suitable antidepressant drugs. ECT is a highly ritualised treatment, with considerable potential for a placebo response, and simulated or sham ECT (the use of anaesthetics, with or without muscle relaxants, minus the electrical stimulus) also exerts a powerful antidepressant effect when used to treat people with depression. Frequency and schedules Although schedules of treatment with ECT for depression vary, it is commonly administered twice a week in the UK compared to three times a week in the US (Scott 1995). Evidence from trials comparing the two schedules for depressed people demonstrates that the two are equal in efcacy, though treatments administered three times a week result in faster onset of improvement (Lerer 1995, Shapira 1998). In the past ECT used to be administered daily (Abrams 1967) or many times a day until a state of regression was induced (regressive ECT) (King 1959). These practices are still followed, but by only a few clinicians in some parts of the world (Agarwal 1992). Some clinicians still administer more than one ECT per day or daily ECT for a few days when a rapid response is desired (Maletzky 1986, Agarwal 1992, Andrade 1993). The courses range from four to 12 treatments (Weiner 1994). For people with schizophrenia, it is believed that between 12 and 20 treatments are necessary (Kendell 1981), though it is unclear how prevalent this is in current. Less commonly, it is given fortnightly or monthly as continuation ECT or maintenance ECT, to prevent relapse of symptoms (Scott 1991, Monroe 1991). The frequency of ECT administration also inuences therapeutic outcome and cognitive adverse effects. Stimulus
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Early ECT machines delivered an alternating sine-wave stimulus at mains frequency and constant voltage. Modern machines, however, deliver a constant current, variable frequency, brief -pulse stimulus. This is more efcient than the sine-wave stimulus at eliciting seizures, and utilises less electrical energy. Whether the sinewave stimulus is more effective than brief pulse stimulus in treating depression is debatable (Robin 1982, Andrade 1988, Scott 1992) but the latter is associated with less cognitive adverse effects. Seizure threshold This refers to the minimum electrical stimulus required to elicit a generalised seizure. It has been shown to vary 40-fold between individuals, and to increase over the course of ECT (Sackeim 1991). Factors that raise seizure threshold and make it more difcult to elicit seizures include: the use of benzodiazepine anxiolytics and hypnotic drugs; anticonvulsant medication; anaesthetic drugs; older age; male sex; dehydration; low oxygen saturation of blood and electrical parameters that raise impedance, such as poor contact between electrodes and the scalp. It was initially believed that the production of a generalised seizure was both necessary and sufcient for the antidepressant effect of ECT, as sub convulsive stimuli were without therapeutic benet (Ottosson 1960). Later, it was demonstrated that generalised seizures of adequate duration could be reliably produced but can sometimes fail to demonstrate therapeutic effect in depression (Sackeim 1991). Seizure duration In clinical practice, generalised motor seizures less than 15 seconds long are considered inadequate. Seizures of 25 to 30 seconds duration are desirable and thus monitored. This is done either via EEG, or by observing and timing motor convulsions in extremities or in a forearm isolated from muscle relaxants by an inated blood-pressure cuff (APA 2001). It is now appreciated that there exists a complex interplay between the degree to which the stimulus dose exceeds the seizure threshold, electrode placement, the rate and extent of recovery, and the degree of adverse cognitive effects when ECT is used to treat people with depression. Electrical stimuli just above individually titrated seizure threshold are effective in treating depression with bilateral electrode placements but ineffective with unilateral placements (Sackeim 1987). Increasing the dose further, to 2.5 times seizure threshold, results in faster response with both bilateral and unilateral ECT. Though the efcacy with bilateral electrode placements is still superior; unilateral non-dominant ECT is associated with less severe cognitive effects than bilateral ECT (Sackeim 1993). The stimulus dose needs to be increased to between ve to six times higher than seizure threshold for unilateral ECT to equal bilateral ECT in efcacy in treating depression (Sackeim 2000). Antidepressant use Placebo controlled trials have demonstrated that relapse rates are roughly 20% to 60% in people continuing on antidepressants after
successful treatment with ECT, versus 50% to 84% in people on placebo after ECT (Devanand 1994, Sackeim 2001). In people with depression who have failed to respond to adequate trials of antidepressants before initiation of ECT, only 50% respond to ECT compared to 86% of people who had not failed an adequate trial of antidepressants (Prudic 1990). Relapse rates are also higher and more rapid in medication resistant depressed individuals who are successfully treated with ECT. Such individuals are also less responsive to continuation pharmacotherapy (Devanand 1994, Sackeim 2001). Symptoms It is uncertain whether the factors detailed above have any bearing on the outcome of ECT when applied to people with schizophrenia. It is also not clear at present which group of people with schizophrenia is most likely to benet from ECT. It is held that people with schizophrenia who have prominent depressive symptoms, positive symptoms or catatonic symptoms of recent onset, are most likely to respond to ECT (APA 2001). In the light of the reputed efcacy of ECT for affective disorders (depression and mania), it is possible that this treatment benets those with schizophrenia solely by modifying affective symptoms and does not modify symptoms such as delusions, hallucinations or disordered thinking (Johns 1995). In addition, those with poorly dened illness, such as the chronically/seriously mentally ill/disordered, may also be given ECT. However it is possible that this diagnostically heterogeneous group has a differential response to the treatment due to inclusion of people with either chronic or psychotic affective disorder or treatment resistant illnesses. Other physical methods of treatment Apart from ECT, other physical methods of treatment in use for people with schizophrenia include electric acupuncture convulsive therapy (Xue 1985). This is a treatment used in China and is a procedure that resembles ECT but delivers different electrical stimulus frequencies and intensities via acupuncture needles, clips, plates and other forms of electrodes to direct the stimulus to the brain at acupuncture points on the head. More recently, repetitive transcranial magnetic stimulation (rTMS), has been used to treat people with psychiatric disorders (Daskalakis 2002). In this procedure, non-invasive stimulation of the brain is achieved by the use of alternating magnetic elds to induce electric currents in the brain, that depending on the frequency of these elds, either excite or inhibit stimulated areas. Studies of rTMS in depressive disorders and obsessive compulsive disorders are covered in other Cochrane reviews (Martin 2002, Martin 2003). Another therapy still in its infancy is magnetic seizure therapy (MST}. This involves the use of high-intensity rTMS to elicit seizures like with ECT, but with less potential for cognitive decits, since rTMS offers greater control over sites stimulated and current densities (Burt 2002). An alternative approach to treating mental disorders is to stimulate the vagus nerve in the neck via an implanted device similar to a
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cardiac pacemaker. As opposed to electroconvulsive therapy, vagus nerve stimulation (VNS) is not associated with cognitive impairment, and has shown some promise in the treatment of depressive disorders (Goodnick 2001). Finally, high-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g. Parkinsons disease, essential tremor, and dystonia), and is being increasingly used in treatment refractory psychiatric disorders (Kopell 2004). Earlier versions of this review addressed four questions with regard to the use of ECT for those with schizophrenia: 1. Does ECT have a benecial effect, and if it does, do particular subgroups of people with schizophrenia exist who are most likely to respond to this treatment? 2. How does ECT compare with antipsychotic drug treatments? i.Does it increase the rate and/or extent of clinical recovery in people treated with drugs? ii.Does concurrent antipsychotic medication improve the efcacy of ECT? iii.Is ECT effective in those whose illness is non-responsive to antipsychotic medication? 3. Do factors related to the administration of ECT affect efcacy and adverse effects? Do the stimulus waveform, stimulus intensity, electrode placement, frequency and number of treatments alter the rate and/ or extent of clinical recovery? 4. Does continuation and/or maintenance ECT reduce the risk of relapse? 5. How does ECT compare in efcacy and safety with other physical treatments used for people with schizophrenia such as electric acupuncture convulsive therapy, vagus nerve stimulation, rTMS, and deep brain stimulation? This version does not cover comparisons of magnetic seizure therapy (MST) with ECT in those with schizophrenia. We hope to cover this in future versions of this review.
2.1 With well dened schizophrenia as opposed to those with less rigorously dened schizophrenia, with the assumption that the latter group will have a greater affective component to their illness and be more responsive 2.2 With catatonic (stupor or excitement) schizophrenia 2.3 With schizophrenia characterized by predominant delusions and hallucinations (positive symptoms) as opposed to social withdrawal, apathy and emotional unresponsiveness (negative symptoms) 2.4 Who are early in the course of their illness (less than two years) 2.5 Who are diagnosed as suffering from schizoaffective disorder as opposed to those with pure schizophrenia 2.6 Who are also on antipsychotic drugs 2.7 Who have not responded to antipsychotic drugs and are considered treatment resistant 2.8 Who have undergone a long (more than 12) or short (12 or less) course of ECT 2.9 Who have more frequent treatments than those who have less frequent treatments 2.10 Who are treated with unilateral compared to bilateral ECT 2.11 Who are treated with threshold level compared to suprathreshold level electrical stimuli 2.12 Who are given continuation or maintenance ECT.
METHODS
Criteria for considering studies for this review
Types of studies We included all relevant randomised controlled trials.
Types of participants
OBJECTIVES
1. Our primary objectives were to determine whether ECT results in clinically meaningful benet with regard to global improvement, changes in mental state, hospitalisation, behaviour and functioning for people with schizophrenia, in the short term (less than six weeks), medium term (six weeks to six months) and long term (more than six months). 2. Our secondary objectives were to determine whether ECT produces a differential response in people:
We included those with shizophrenia, schizoaffective disorder or chronic mental disorder (non-affective), diagnosed by any criteria.
Types of interventions 1. ECT (modied or unmodied) - any dose, frequency, level of stimulus against one or more of the following: 2. ECT (modied or unmodied) - threshold dose vs greater than threshold dose 3. ECT (modied or unmodied) - Unilateral vs bilateral
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4. ECT (modied or unmodied) - given 3 days / week vs given more or less than three days per week 5. ECT (modied or unmodied) - course of 12 treatments vs course of over 12 treatments to 30 treatments vs continuation treatment 6. Placebo 7. Sham ECT or simulated ECT (the procedure of ECT minus the electrical stimulus) or subconvulsive ECT (with an electrical stimulus but without the induction of a seizure) 8. Pharmacological interventions such as antipsychotics, or other drug treatments 9. Non-pharmacological interventions such as psychotherapy, social casework or milieu therapy 10. Electric acupuncture convulsive therapy 11. Repetitive transcranial magnetic stimulation 12. Vagus nerve stimulation 13. Deep brain stimulation Types of outcome measures The outcomes of primary interest were as follows: 1. Clinically meaningful benets in overall functioning 2. Changes in mental state, hospitalisation status, behavioural, social and occupational functioning 3. Remission of symptoms, however dened 4. Discharge from hospital or care As various scales were used for each primary outcome, the definition of clinically meaningful benet was obtained from the validation of the original scale. Where possible, data were made binary in order to generate relative risks. If this was not possible, continuous data was evaluated and the clinically meaningful benet of changes assessed in the light of the original validation of each scale. Secondary outcome measures used were: 1. Premature withdrawal of people from the trial by a decision of (i) the person in the trial, or (ii) the researchers; and 2. Any adverse event during the course of treatment or within the period of follow up. We reviewed each outcome during the ECT course, in the short term (less than six weeks), medium term (six weeks to six months), and long term (over six months).
[and (ECT or electroconvuls* or electro-convuls* or electroshock* or electro-shock*)] 1.2 We searched the Cochrane Schizophrenia Group Specialised Register (July 2004) using the phrase: {(ECT * in title, or * ECT * abstract, index or title terms of REFERENCE] or (ECT and (transcranial*, (*electro* and *acupuncture*), or (*deep* and *brain*) or (*vagus* and *nerve*) or [Electroconvulsive* in interventions of STUDY]} The Cochrane Schizophrenia Group Specialised Register is based on regular searches of BIOSIS Inside, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO, hand searching of relevant journals and conference proceedings, and searches of several key grey literature sources. 1.3 Current Controlled Trials We searched this data base (November 2004) for ongoing trials using the terms schizophrenia AND *ECT* or *transcranial* or (*deep* and *brain* ) or (*vagus* and *nerve* ). 2. Reference searching Once a study was selected (see below), we searched citations for additional trials. We contacted the rst author of each trial published since 1980 for additional references and for unpublished trials. We also searched the references cited in narrative reviews and guidelines (Andrade 2002, APA 1990, APA 1995, APA 2001, Fink 1991, Fink 1996, Johns 1995, Kruger 1995, Lock 1995a, NICE 2003, NIMH 1976, Salzman 1980). We additionally hand searched the Indian Journal of Psychiatry (January 1960 - October 2004) for controlled trials of ECT. 3. Personal contact We contacted manufacturers of ECT machines and members of the editorial board of the journal Journal of ECT. We also sought all selected studies as a citation on ISI database in order to identify more studies.
Data collection and analysis

1. Selection of trials We independently assessed every report identied by the electronic search for relevance to this review. In cases of disagreement we obtained the article and independently assessed each article for relevance to the review. We resolved any arising disagreements by discussion and where there was still doubt, we added the study to those awaiting assessment and contacted the study authors for further clarication. Failing a satisfactory result, we excluded the study from the review. 2. Assessment of methodological quality We independently assigned each selected trial to quality categories described in the Cochrane Collaboration Handbook (Alderson 2004). Only trials assigned to categories A and B were selected and those assigned to category C were excluded. In case of disagreement, we sought clarication from the authors of the trial and added these to the list of those awaiting assessment.
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Search methods for identication of studies

1. Electronic searching 1.1 We searched Biological Abstracts (January 1966 to January 1996), EMBASE (January 1980 to January 1996), MEDLINE (January 1966 to November 2004) and PsycLIT (Tier 1 and 2 as specied in the Cochrane Schizophrenia Groups Search Strategy) (January 1974 to January 1996) using the Cochrane Schizophrenia Groups phrase for randomised controlled trials for schizophrenia (see Search Strategy) with the addition of:
3. Data management 3.1 Data extraction We independently extracted data. Prathap Tharyan (PT) undertook all data extraction and Clive Adams (CEA) checked ten percent of this work. We attempted to resolve any disagreement by discussion. Where disagreement persisted and published results made data extraction difcult, we attempted to obtain clarication from the authors of the trial, pending which the trial was assigned to those awaiting assessment. 3.2 Binary outcomes Where binary outcomes (proportions) were used, we calculated relative risks (RR), xed and condence intervals for each outcome. In addition we calculated absolute measures, the number needed to treat (NNT) and number needed to harm (NNH). We undertook analyses on an intention to treat basis. 3.3 Continuous outcomes We excluded continuous data if more than 50% of people were lost to follow up. We reported continuous data as presented in the original studies without making any assumptions about those lost to follow up. For continuous outcomes, we calculated pooled weighted mean differences (WMD) and condence intervals for outcomes using similar scales. 3.3.1 Validity of continuous measures We only included continuous data from rating scales if the measuring instrument had been described in a peer-reviewed journal and the instrument was either a self report or completed by an independent rater or relative (not the therapist). Unpublished instruments are more likely to report statistically signicant ndings than those that have been peer reviewed and published (Marshall 2000). 3.4 Leaving the study early People dropped out of each of the studies of their own volition or as a result of a decision made by the trialists. For binary outcomes, we assigned people who left of their own accord to the least favourable outcome group. We tested the effects of this assignment in a sensitivity analysis. 3.5 Normal distribution of continuous data Data on continuous outcomes are often not normally distributed. To avoid the pitfall of applying parametric tests to non-parametric data, all data included in the review met the following criteria: i. standard deviations and means were reported in the paper or were obtainable from the authors; ii. when a scale started from 0 the standard deviation (SD), when multiplied by two was less than the mean (as otherwise the mean was unlikely to be an appropriate measure of the centre of the distribution, Altman 1996). iii. if a scale started from a positive value (such as PANSS that can have values from 30 to 210) the calculation described above in ii) was modied to take the scale starting point into account. In these cases skewness was considered present if 2SD>(S-Smin), where S is the mean score and Smin is the minimum score. Data that did not meet these standards were not entered into the
RevMan software (which assumes a normal distribution). However, we reported data not meeting these criteria in additional tables and in the text if they had been analysed with appropriate non-parametric tests. 3.6 Endpoint versus change data Where possible we presented endpoint data, and if both endpoint and change data were available for the same outcomes, then we reported only the former. 3.7 Presentation of data Where possible, we entered data in such a way that the area to the left of the line of no effect indicated a favourable outcome for the intervention of interest. For some scales a high score indicates a bad outcome, but for others, high scores indicate a positive outcome. In the case of the latter, the area to the left of the line indicates a favourable outcome for the control group and is labelled accordingly. 3.8 Cluster trials Studies increasingly employ cluster randomisation (such as randomisation by clinician or practice) but analysis and pooling of clustered data poses problems. Firstly, authors often fail to account for intra class correlation in clustered studies, leading to a unit of analysis error (Divine 1992) whereby p values are spuriously low, condence intervals unduly narrow and statistical signicance overestimated. This causes type I errors (Bland 1997, Gulliford 1999). Where clustering was not accounted for in primary studies, we presented the data in a table, with a (*) symbol to indicate the presence of a probable unit of analysis error. In subsequent versions of this review we will seek to contact rst authors of studies to obtain intra class correlation co-efcients of their clustered data and to adjust for this by using accepted methods (Gulliford 1999). Where clustering has been incorporated into the analysis of primary studies, we will also present these data as if from a noncluster randomised study, but adjusted for the clustering effect. We have sought statistical advice and have been advised that the binary data as presented in a report should be divided by a design effect. This is calculated using the mean number of participants per cluster (m) and the intra-class correlation co-efcient (ICC) Design effect = 1+(m-1)*ICC (Donner 2002). If the ICC was not reported it was assumed to be 0.1 (Ukoumunne 1999). 4. Heterogeneity After considering the likelihood of clinical heterogeneity based on comparisons of the included studies, we supplemented graphical display of results with the Mantel-Haenszel chi-square test of heterogeneity to check whether differences in results were due to chance alone. Since this test has low power to detect heterogeneity, a signicance level less than 0.10 was interpreted as evidence of heterogeneity. In addition, for this version of the review, we quantied inconsistency across studies and its impact on the meta-analysis by examining the value of I-squared to estimate the percentage of variability due to heterogeneity rather than chance alone. We interpreted an I-squared value of 50% or greater as indicating
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substantial levels of heterogeneity (Deeks 2003, Higgins 2003). If heterogeneity was detected but not quantied as contributing substantially to variation in data, all data were pooled and interpreted using the random-effects model. If inconsistency was substantial, data from the responsible studies were not pooled and the results were presented separately and reasons for heterogeneity were explored. In any event, if substantial heterogeneity was present, we undertook a sensitivity analysis to the presence or absence of these data. 5. Sensitivity and subgroup analysis We undertook sensitivity analyses in all instances when heterogeneity was detected. The effect of including studies with high attrition rates was also analysed in a sensitivity analysis. In addition, it was hoped that differences in outcomes would be detected for (a) people with operationally dened schizophrenia as opposed to those diagnosed by clinical consensus, (b) people with varying degrees of treatment resistance and those whose illness was not designated as such, (c) people having predominantly positive or negative symptoms of schizophrenia and those without this designation, and (c) people who had been ill for less than two years and those at a later stage of their illness. 6. Publication bias When outcomes included data from ve or more trials, we entered data into a funnel graph (trial effect versus trial size) in an attempt to investigate the likelihood of overt publication bias.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies. For detailed descriptions of individual studies please see Characteristics of included and excluded studies tables. 1. Excluded studies Many studies that we found by the search strategy were so clearly irrelevant that is was not necessary to report them in the excluded studies table. In the excluded studies table we describe the 105 studies (120 reports) that had to be inspected in hard copy in order to decide on their relevance. Of these, 21 were described as randomised controlled trials, though nine were quasi randomised. Of the 17 that were randomised, seven reported comparisons, four involved participants, and one reported outcomes not relevant to this review. Four relevant randomised trials had to be excluded due to lack of any usable data (Gambill 1966, Langsley 1959, Natani 1983, Reichert 1976). Gambill 1966 compared ECT with antipsychotics and with sham ECT. Langsley 1959 compared chlorpromazine with ECT. Natani 1983 evaluated both ECT with and without antipsychotics, and antipsychotics alone. Reichert 1976 compared unilateral with bilateral ECT. Of the non-randomised
studies, 45 were controlled trials, 30 were case series or reports, seven were retrospective chart reviews and two were narrative reviews. 2. Awaiting assessment Yao 2000 is described as randomised and compared ECT with subconvulsive ECT but presented no usable data; we hope to obtain more details from the authors. 3. Ongoing studies We identied one ongoing multi-centre, open label randomised trial in the US of ECT in people with schizophrenia resistant to clozapine (Petrides 2000). The trialists hope to randomise 64 people with schizophrenia aged 18 to 65 years who have not responded to at least two trials of antipsychotic drugs given at doses equivalent to 400 mg of chlorpromazine. Another condition of trial entry is that these people continue to have substantial psychotic symptoms despite at least 12 weeks of treatment of clozapine (at least eight weeks at a consistent dose). These people were to receive ECT and clozapine or clozapine alone. Recruitment commenced in 2000 and completion was expected by November 2003, but available information suggests that the study was still recruiting participants in November 2004. 4. Included studies We identied 26 studies (50 reports) for inclusion in this version of the review. There was considerable variation between trials in the: clinical and demographic prole of the participants; criteria used to establish the diagnosis of schizophrenia; methods of administering ECT; comparisons and outcome measures used; duration of follow up and treatments given during follow up. 4.1 Participants 4.1.1 Diagnoses Fifteen of the 26 trials used operationally dened criteria to establish the diagnosis of schizophrenia. The remainder diagnosed the disorder by clinical consensus. Diagnostic criteria used included ICD 9, ICD 10, DSM III R, DSM IV, Feighners criteria, Present State Examination and CATEGO Research Diagnostic Criteria, and the Chinese Medical Council Clinical Diagnostic Criteria. Ungvari 1982 classied participants based on the classication of Leonhard 1979 into systematic and unsystematic schizophrenia; a classication similar to the process and reactive or non-process classication of Langfeldt 1960. Three trials included people with homogenous clinical subtypes of schizophrenia, namely chronic catatonic schizophrenia or non-affective catatonia (Miller 1953, Girish 2003) and paranoid schizophrenia (Taylor 1980). One trial, Sarkar 1994, included only young males with schizophreniform disorder. Wu 1989 included 12 people with unspecied psychosis among the 40 participants in the trial. None of the included trials studied people with schizoaffective disorder. 4.1.2 Age and gender The participants in all included trials were adults; none were children or adolescents. Abrams 1967, Wu 1989 and Sarkar 1994 included only men, while Baker 1958 and Baker 1960 included only women.
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4.1.3 Treatment resistant schizophrenia Chanpattana 1999a, Chanpattana 2000 and Goswami 2001 included people with treatment resistant schizophrenia that fullled modied criteria for treatment resistant schizophrenia (Kane 1988). Agarwal 1985, Baker 1960 and Taylor 1980 also included participants who had failed to respond to antipsychotics, though it is uncertain how many would meet stringent criteria for treatment resistance. The other trials included people with varying degrees of non-response to conventional antipsychotics, though Abrams 1967, Sarkar 1994, and possibly Ungvari 1982 included people who were acutely ill and hence unlikely to be resistant to treatment. 4.1.4 Duration of disorder Little homogeneity was evident between trials in the duration of the disorder. Six trials stipulated a duration of less than two years, and of these, Abrams 1967 and Sarkar 1994 included participants with onset of disorder of less than three months and two months respectively. Five trials included participants who had been ill for more than two years and two of these trials (Naidoo 1956, Miller 1953) included individuals with chronic illness hospitalised for ten years or more, with the former including some individuals who had also been treated with leucotomy. Thirteen trials included people with varying duration of the disorder ranging from one month to thirty-two years. From the reports of Bagadia 1981 and Baker 1960, it was unclear how long the participants had been ill. 4.2 Setting Eleven of the included trials were conducted in India, ve in the USA, four in the UK, two in Thailand, one each in Canada, China, Hungary and Nigeria. Chanpattana 1999a utilised two and Chanpattana 2000 three sites, while the remaining trials were conducted at single sites. Eighteen of the trials were conducted in hospital, four included only outpatients and four included both outpatients and inpatients. 4.3 Study size The 26 trials in this review involved 1485 participants of whom 798 were treated with ECT. May 1968 had the largest number of participants, (247), while Abrams 1967 included only ten. Seven trials had less than 30 participants, eight randomised between 30 and 50 individuals, ten included between 51 and 100, and only one study had more than 100 participants. 4.4 Length of trials The period of follow up in the included trials varied from six days (Ungvari 1982) to ve years (May 1968). Fifteen of the trials conducted end point evaluations within a week after the course of ECT, and courses of treatment varied from six days to 12 weeks. Eight trials reported follow up periods of up to six weeks, thirteen trials followed up participants for between six weeks to six months and only ve trials had follow up periods of greater than six months. Of these, Brandon 1985 followed participants for 26 weeks after the course of ECT, Sarkar 1994 for six months, and Small 1982 evaluated outcomes over 12 months. Chanpattana 1999a evaluated continuation ECT over a six-month period for
people with treatment resistant schizophrenia. The remarkable trial by May 1968 had a follow-up period of three to ve years. The interpretation of the long-term effects of treatments in this trial is limited by the naturalistic follow-up and uncontrolled treatment conditions, which in some instances included further ECT. 4.5 Interventions There was considerable variation in the quality of reporting of details of the administration of ECT. Fifteen of the trials described that ECT was modied, while seven appear to have used unmodied ECT. From three reports it was unclear whether or not ECT was modied. The trials by Chanpattana 1999a and Chanpattana 2000, Girish 2003, Goswami 2001, Sarita 1998, Taylor 1980 and Ukpong 2002 stated that brief pulse ECT devices were used; the remainder appear to have used sine-wave machines. The quality of reporting on electrode placement, frequency and duration of ECT administration was generally adequate in the selected trials. With the exception of seven out of the 26 studies, little information was provided in the trial reports on methods used to ensure adequacy of treatments with ECT. Chanpattana 1999a and Chanpattana 2000 titrated individual thresholds for participants and monitored seizures with the cuff method and EEG recordings. Girish 2003, Goswami 2001 and Sarita 1998 used suprathreshold stimuli and monitored motor and electrical seizure activity as above. Sarkar 1994 used sine-wave stimuli at settings sufcient to ensure seizures of 25 seconds or more, and Ukpong 2002 delivered xed brief pulse stimuli. These two trials monitored motor seizures in a forearm isolated from muscle relaxant by an inated blood-pressure cuff. 4.5.1 Comparisons ECT was compared with other interventions in 23 trials, while three trials addressed various aspects of the practical administration of ECT that were considered to potentially alter outcome. 4.5.1.1 ECT versus Sham ECT Twelve trials compared ECT with sham ECT. All but two trials also used additional antipsychotic drugs (chlorpromazine, haloperidol, or triuoperazine). (Brill 1959, Miller 1953). Bagadia 1981 used additional chlorpromazine only for people given sham ECT, while participants allocated to ECT were given placebo. Similarly Girish 2003 compared ECT plus placebo with risperidone plus sham ECT 4.5.1.2 ECT versus placebo Naidoo 1956 had a trial arm that compared ECT plus placebo with placebo. Small 1982 had a trial arm that compared combined ECT with antipsychotic drug versus placebo. 4.5.1.3 ECT versus antipsychotic drugs Ten trials compared ECT directly with antipsychotic drugs. Five used chlorpromazine as the comparator drug, Small 1982 compared ECT with thiothixine, May 1968 with triuoperazine and Naidoo 1956 used reserpine, a drug that pre-dated chlorpromazine. Girish 2003 compared ECT plus placebo versus risperidone and Sham ECT. Ungvari 1982 compared ECT plus low dose
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haloperidol with very high dose haloperidol, while Janakiramiah 1982 compared ECT in two groups of people treated with low dose and high dose chlorpromazine, with two other groups given the two strengths of the drug without ECT. There was some variability in the doses of antipsychotics used in these trials, as well as in the trials of ECT versus sham ECT that used concurrent antipsychotics. Taylor 1980 and Brandon 1985 used doses of antipsychotics that were lower than those used in the other trials and lower than those currently recommended for acute phase treatment in people with schizophrenia. 4.5.1.4 ECT versus psychotherapy and milieu therapy May 1968 compared ve treatment conditions for those with schizophrenia: bilateral ECT; antipsychotic drugs alone or in combination with psychoanalytic psychotherapy; psychoanalytic psychotherapy alone and milieu therapy. We were unable to nd any trials that compared ECT with other forms of psychotherapy, psychological or psychosocial interventions. 4.5.1.5 ECT versus insulin coma One early trial compared ECT with insulin coma (Baker 1958), a treatment in vogue when ECT was introduced to psychiatric practice. 4.5.1.6 Continuation ECT Chanpattana 1999a compared continuation ECT with and without upentixol versus upentixol alone, over a six-month period, for people with treatment resistant schizophrenia who had responded to an open trial of ECT and upentixol. We were unable to nd any randomised trials of the use of maintenance ECT in schizophrenia (where the ECT is continued for even longer than six months). One excluded study (Chanpattana 1998) described a case series treated with maintenance ECT and another from the same research group described a non-randomised open trial of maintenance ECT (Chanpattana 2000b). 4.5.1.7 Unilateral versus bilateral ECT Two of the included trials compared unilateral with bilateral ECT (Bagadia 1988, Doongaji 1973) without concurrent antipsychotic drugs. Sarita 1998, on the other hand, involved trial arms that compared unilateral with bilateral ECT for people who also had been given concurrent haloperidol. 4.5.1.8 Frequency of treatments One trial (Abrams 1967) compared unilateral ECT given daily for ve days per week with unilateral ECT given three times a week without concurrent antipsychotics. Trials of regressive ECT (King 1958, King 1959, King 1960) were excluded, as allocation was sequential in all three. Ungvari 1982 delivered ECT twice a day on alternate days over six days. ECT is more commonly given two or three times a week together with concurrent antipsychotic drugs and we were unable to nd any randomised trials of ECT directly comparing these frequencies. Among the excluded trials was one study that was a retrospective chart review of matched ECT responders who were part of an earlier randomised trial drawn from two hospitals that used either twice or three times weekly treat-
ments (Chanpattana 1999d). 4.5.1.9 Number of treatments The included trials used varying numbers of ECT, ranging from ve to 45 treatments. However, Baker 1960 directly compared xed courses of 12 versus 20 ECT given at different frequencies without concurrent antipsychotics. 4.5.1.10 Stimulus intensities Chanpattana 2000 compared ECT given at stimulus intensities just above individually titrated seizure thresholds with ECT given at twice seizure threshold and four times greater than seizure threshold. All participants in this study were resistant to conventional antipsychotics but were nevertheless treated with upentixol. 4.6 Outcomes 4.6.1 Global improvement Eighteen trials presented data on global impressions of improvement, and for the majority we extracted data to dichotomise this outcome. Eight trials used Clinical Global Impression (CGI) scale, but two (Abraham 1987, Janakiramiah 1981) presented CGI data as continuous measures without standard deviations. The rst author of Abraham 1987 provided dichotomised CGI data for this version of the review but we were unable to use data for global improvement from the latter trial. We derived data on global improvement for Small 1982 based on the proportions of those for whom the study was terminated due to non-response or to clinical deterioration. Chanpattana 1999a, Chanpattana 2000 and Small 1982 used the Global Assessment of Functioning (GAF) scale to assess global improvement, though the latter two trials reported no usable data on this measure. Chanpattana 2000 also dened global improvement as reduction in Brief Psychiatric Rating Scale (BPRS) scores of <25 after ECT maintained over a three-week stabilisation period. Sarkar 1994 used a ve point Global Assessment Scale to categorise global outcome. May 1968 used the Meninger Health Sickness scale to assess initial and end point global status. Girish 2003 provided data on the number of participants in each trial arm who required more ECT at the end of the three-week trial, and we used this to assess global improvement. 4.6.2 Mental state Fourteen trials assessed mental state with the BPRS, though data using this measure from Bagadia 1988 and Janakiramiah 1982 were unusable since they presented only mean scores without standard deviations. Chanpattana 2000 and Small 1982 did not present BPRS data in an extractable form. Bagadia 1981, Sarkar 1994 and Ukpong 2002 did report both means and standard deviations. For Sarkar 1994 this was provided by the rst author, but data from all three were skewed and we did not add them to comparisons but reported them in additional tables. Some trials used other scales to assess mental state, but with the exception of May 1968, data from these scales were not usable (see Included studies table for details). 4.6.3 Behaviour May 1968, Miller 1953 and Small 1982 used nurse rated behaviour
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scales, but data from the latter two trials were not usable. We extracted behavioural data from the former trial for both the short and medium term. 4.6.4 Employment Miller 1953 provided data on employment while in hospital, and while May 1968 provided some data on employment during follow up, this was unusable. 4.6.5 Discharge Baker 1958 and May 1968 provided data on numbers of participants who were discharged post interventions, based on clinicians overall impressions about their tness for discharge. 4.6.6 Leaving the study early We obtained data from 22 of the 26 included trials on the numbers of those who left the trials early. Reasons for losses from trials were not always available. Two trials were notable for the large numbers of participants who left early. Bagadia 1988 lost 21/61 participants (35%) over the 20 day trial, and Doongaji 1973 lost 32/86 participants (37%) by end of the course of ECT, and only 25 completed the three month follow up (70% drop out). Neither of the trials provided the numbers of those participants initially allotted to the different interventions, and both only presented data for those who completed the trial. For this reason, we were unable to use an intention-to-treat analysis in these two instances. Nor were we able to use data from these trials for the outcome leaving the study early. Data from these two trials were eliminated in a sensitivity analysis. Only one trial (Chanpattana 2000) provided data for both intention-to-treat and completer samples, and in keeping with our pre-stated protocol, we used the scale derived outcomes provided for mental state, global functioning, and cognitive adverse effects for the intention-to-treat sample provided. The primary analysis, performed on the two samples by the trialists, revealed similar results. 4.6.7 Relapse ECT is a treatment that is usually discontinued once clinical improvement is observed, and schizophrenia is a disorder with a relapsing course in the absence of continuous treatment. Relapse rates after successful ECT are therefore an important indicator of the efcacy of ECT. Trials provided details on relapse in the short term (Abraham 1987, Brandon 1985), medium term (Taylor 1980), and long term (May 1968) against sham ECT. Baker 1958 reported relapse rates in the short term for people treated with ECT versus those treated with antipsychotics and insulin coma. Chanpattana 1999a provided details of relapse over six months in people with treatment resistant schizophrenia treated with continuation ECT, with or without antipsychotics, versus antipsychotics alone. Abraham 1987, Baker 1958, Brandon 1985 and Taylor 1980 did not pre-dene relapse, but appear to have used clinical appraisal of deterioration in clinical condition to record relapses. For May 1968, we used re-hospitalisation data within two years as a proxy measure for relapse over the long term. Chanpattana 1999a used stringent criteria to dene relapse, pre-stating that BPRS scores of at least 37 that persisted for two consecutive rat-
ings done three days apart would be deemed a relapse. 4.6.8 Adverse effects A number of trials assessed participants for adverse effects, notably cognitive events such as memory impairment, though some information was also provided for other events. 4.6.8.1 Cognitive adverse effects Most of the trials that assessed memory functions after ECT did so using sub-tests from validated neuropsychological test batteries that evaluated visual and verbal memory. Sarita 1998 compared paired associate learning and visual memory after the interventions between people treated with ECT and sham ECT. Bagadia 1981 reported subjective forgetfulness and objective evidence of cognitive impairment in the short term for people on placebo and ECT, versus those on sham ECT and antipsychotics. Wu 1989 assessed short-term memory in people treated with ECT versus those on antipsychotics. The assessments were made before and immediately after ECT, as well as nine weeks after the course of ECT. Chanpattana 1999a used the relatively insensitive but commonly used Mini Mental State Exam (MMSE) over a six month course of continuation ECT. We extracted categorical data on subjective and objective memory functions (Bagadia 1988) and continuous data on visual and verbal memory (Sarita 1998) for the comparison of unilateral and bilateral ECT. Abrams 1967 reported categorical clinical and neuropsychological test data on memory impairment for people treated with unilateral ECT three and ve times a week. Chanpattana 2000 assessed cognitive functions using the MMSE on people treated with different stimulus intensities but we were unable to use the data provided as the senior authors were not able to supply this information. In the comparison of 12 versus 20 treatments, Baker 1960 presented no data on memory impairment. Since the trials used different tests and different comparisons, we were unable to synthesise data from trials so we have presented them separately. 4.6.8.2 Other adverse effects Ungvari 1982, Bagadia 1981 and Girish 2003 provided data on adverse effects, mainly acute extrapyramidal adverse effects produced by antipsychotics in people treated with and without ECT. 4.6.9 Death Only May 1968 explicitly provided data on mortality after ECT over the long term. 4.7 Outcome scales A number of outcomes used in this review presented continuous data derived from a variety of measuring instruments/scales. Brief details of the various scales used in this review are provided below. 4.7.1 Brief Psychiatric Rating Scale (BPRS, Overall 1962) This is a brief rating scale used to assess the severity of a range of psychiatric symptoms, including psychotic symptoms. The original scale has 16 items (although a revised 18-item scale is commonly used). Each item is dened on a seven-point scale varying from not present to extremely severe, scoring from 0-6 or 17. Total scores can range from 0-126, with high scores indicating more severe symptoms. Ukpong 2002 used a modied nine-item
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version of this scale. Hamilton Rating Scale for Depression (HRSD/HAM-D, Hamilton 1960) The instrument is designed to be used only on patients already diagnosed as suffering from affective disorder of depressive type. It is used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information. The scale contains 17 variables measured on either a ve-point or a three-point rating scale, the latter being used where quantication of the variable is either difcult or impossible. Among the variables are: depressed mood, suicide, work and loss of interest, retardation, agitation, gastro-intestinal symptoms, general somatic symptoms, hypochondriasis, loss of insight, and loss of weight. It is useful to have two raters independently scoring a patient at the same interview. The scores of the patient are obtained by summing the scores of the two physicians. A score of 11 is generally regarded as indicative of a diagnosis of depression. 4.7.2 Bush-Francis Catatonia Rating Scale (BFCRS, Bush 1996) This 14-item scale scores the presence of catatonic signs such as: excitement, stupor, mutism, staring, posturing, mannerisms, negativism and withdrawal. Higher scores indicate more catatonic signs. 4.7.3 Clinical Global Impression (CGI, Guy 1976) This rating instrument is commonly used in studies on schizophrenia and enables clinicians to quantify severity of illness and overall clinical improvement during therapy. A seven point scoring system is usually used with low scores indicating decreased severity and/ or greater recovery and higher scores indicating increased severity and/or clinical worsening. Modications of this instrument were used by some identied trials and this review dichotomized the data into the categories improved or not improved. 4.7.4 Global Assessment of Functioning (GAF, APA 1995) This modied version of the Global Assessment Scale (Endicott 1976) is itself a revision of the Health Sickness Rating Scale (Luborsky 1962). It considers psychological, social and occupational functioning on a hypothetical continuum of mental healthillness and is rated from 0-100. Higher scores indicate a better outcome. 4.7.5 Jenkins Symptom Rating Scale (JSRS, Jenkins 1959) This scale quanties symptoms and behaviour with a high score indicating a poor outcome. It is a modied abbreviated version of the Lorr Scale (Lorr 1953) and was used by May 1968. This scale is not commonly used today. 4.7.6 Meninger Health Sickness Scale (MHS, Luborsky 1962) This scale, developed from psychotherapy research, denes health by comparing people under consideration with a standard series of patients graded in degrees of mental health. High scores indicate good outcome. This was used by May 1968 to provide initial and terminal clinical global status but is not presently in common use. 4.7.7 Mini Mental State Examination (MMSE, Folstein 1975) This clinician-administered clinical evaluation assesses cognition
in ve areas: orientation; immediate recall; attention and calculation; delayed recall, and language. The test takes 15 minutes to administer and the score ranges from 0 (severe impairment) to 30 (normal). The Thai version of the MMSE (Kongsakon 1994) was used in the Chanpattana 1999a and Chanpattana 2000 studies. 4.7.8 Motility Affect Cooperation Communication Scale (MACC, Ellsworth 1959) This scale measures behaviour and social adjustment and was developed to be used by nursing staff with high scores indicating a good outcome. Though used by May 1968, it is not commonly used at present. 4.7.9 Scale for the Assessment of Negative Symptoms (SANS, Andreasen 1982) This is a six-point scale providing a global rating of the following negative symptoms: alogia; affective blunting; avolition-apathy; anhedonia-asociality and attention impairment. Higher scores indicate more symptoms. 4.8 Missing outcomes None of the included trials provide details of participants satisfaction with ECT, quality of life, or economic evaluations.
Risk of bias in included studies

The 26 studies that met the inclusion criteria for this review spanned ve decades with considerable variations in methodological quality. 1. Randomisation All the included trials were described as randomised but only May 1968 described the process of randomisation adequately. Subsequently to the initial publication of this review, senior authors of Chanpattana 1999a, Chanpattana 2000, Goswami 2001, Sarkar 1994 and Girish 2003 provided further details as to how randomisation took place and these ve trials were nally assigned a quality assessment score of A. This may indicate problems in the quality of reporting in the other trials, rather than genuine inadequate concealment of randomisation. Doongaji 1973, and Taylor 1980 used stratied randomisation. Small 1982 randomised within a pre-designated ratio and Abrams 1967 randomised participants by the toss of a coin. 2. Blinding Fifteen of the 26 trials were described as double blind. This included 11 of the 13 trials comparing ECT with sham ECT. Eight trials used only blind raters, though Janakiramiah 1982 reported that rater blindness was compromised in a dozen instances. Abrams 1967 did not describe blinding, and in all probability this trial was unblinded. It was unclear from Baker 1958 and Baker 1960 whether raters were blind. The design of some of the trials precluded blinding of participants, especially the trials comparing ECT with antipsychotics. Due to this fact, Naidoo 1956 and Small 1982 involved people who were blinded with respect to placebo and antipsychotics, but not to ECT, while raters were
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blind to the nature of all interventions. None, except Doongaji 1973, attempted to formally evaluate the blindness of raters. 3. Leaving the study early In general, few people were lost to follow up in most of the included studies, with the notable exception of Bagadia 1988 and Doongaji 1973. Both of these trials assessed unilateral versus bilateral ECT and involved outpatients. Both failed to report participants reasons for leaving the study early, and both lost people during the course of ECT. The trial with the longest follow up, May 1968, lost 186/247 (70%) of participants over the ve year follow up period, though in the medium term only 19 people (8%) left the trial. 4. Quality of reporting There was considerable variation in the quality of reporting of results. Studies frequently presented both dichotomous and continuous data in graphs, or as the results of analyses such as survival analysis or analysis of variance, or reported only statistical measures of probability (p-values). This often made it impossible to acquire raw data for synthesis. Nine studies presented means for some outcomes with no numerical description of the variance around these averages (standard deviations or standard errors), rendering the results unusable without further data. We were unsuccessful in our attempts to obtain these missing data from trialists. In six trials, although mean and standard deviations were provided, data did not assume a normal distribution precluding further analyses without individual primary data. Bagadia 1981, Baker 1958, Brandon 1985, May 1968, Sarita 1998, Sarkar 1994). Chanpattana 2000, Small 1982 and Girish 2003, presented data for primary outcomes in a form that made data extraction impossible. The senior authors of the rst two trials are unable to provide usable data but we hope to obtain usable data from Girish 2003 for inclusion in future versions of this review. The trial by Bagadia 1988 posed problems in interpretation of the number of participants, as this trial was reported initially as a preliminary report (Bagadia 1981), and later as a completed trial as well as a composite report of both papers. It is unclear whether the results of cognitive tests pertained to the preliminary or nal report. Data for memory impairment from this trial have been taken from the preliminary report while clinical global improvement was obtained from the completed trial (Bagadia 1988).
Effects of interventions
1. The search and trial selection The search from the original version of the review in 1996 yielded 20 reports from 12 trials for inclusion. The second update of the review included 24 trials with forty-six associated reports. Five trials awaited assessment and have since been excluded. Seven trial authors have thus far provided additional and previously unpublished information (Abraham 1987, Chanpattana 1999a, Chanpattana 2000, Goswami 2001, Sarita 1998, Sarkar 1994, Small 1982, Taylor 1980), but we could not obtain usable data on
some primary outcomes from the rst authors of Small 1982 and Chanpattana 2000. Goswami 2001 was included in the second update of this review as an unpublished conference presentation, with a manuscript and additional clarication of this trial of ECT versus sham ECT for treatment resistant schizophrenia kindly provided by the trial authors. This trial was subsequently published in 2003 and we used both sources for data for this review. This update includes two additional trials that were published since the update in 2002 (Ukpong 2002, Girish 2003), though continuous data from some primary outcomes are unfortunately skewed and therefore presented in additional tables. We identied one ongoing multicentre randomised open trial of ECT plus clozapine versus clozapine in people with schizophrenia who were resistant to conventional and non-conventional antipsychotics and to clozapine (Petrides 2000). One trial awaits assessment (Yao 2000). If usable data are obtained from trialists, this will be added to the next version of the review. We were unable to include the trials of electro-acupuncture therapy (Gang 1997, Xue 1985). We did not nd any randomised trials comparing ECT with rTMS, vagus nerve stimulation or deep brain stimulation. For the original version of this review, Rochelle Seifas independently assessed trials for inclusion and extracted data from the twelve included trials. Clive Adams undertook trial assessment and data extraction of the newly included trials for subsequent versions, including this update. 2. Limited data There appears to be a shortage of good quality randomised trials to enable data synthesis for some outcomes. Comparisons of ECT with antipsychotics or with non-pharmacological interventions offer very little data. Continuation ECT, comparisons of bilateral with unilateral ECT or different methods of administering ECT continue to be under-researched areas. Nevertheless, the selected trials do provide sufcient data to allow some conclusions to be drawn regarding numbers of participants showing improvement at the end of a course of ECT, when compared to placebo, sham ECT or antipsychotics. Usable but very little data are also available for many important outcomes, such as relapse and discharge from care. None of the selected trials directly addressed the issue of the acceptability of ECT to those treated, although, the numbers of people who left the studies early may serve as an indirect measure of this. 3. Comparisons We extracted data for nine comparisons for this update. Four of these compared courses of ECT with other interventions, one evaluated the efcacy of continuation ECT in people who had already responded to a course of ECT and four assessed different methods of administering ECT. 3.1 ECT versus Sham ECT or Placebo (12 RCTs, 405 participants of whom 212 treated with ECT). 3.1.1 Global improvement Previous versions of this review included Janakiramiah 1982 in
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this comparison but in this version we more appropriately analysed the data from this trial in the comparison of ECT versus antipsychotics. For this update we added unpublished data obtained from authors of Abraham 1987 and Small 1982 on proportions not globally improved to this comparison. Pooled data from ten trials indicated that treatment with ECT was signicantly more likely to result in clinical global improvement at the end of the course than with placebo/sham ECT (n=392, RR 0.71 xed CI 0.59 to 0.86, NNT 6 CI 4 to 12), and though data were heterogeneous (chi-square 17.49 df=9 P=0.04), inconsistency was not substantial (I-squared 48.5%). Using a random-effects model resulted in the expected wider condence intervals without reversing the direction, or substantially reducing the effect estimate (RR 0.76 random CI 0.59 to 0.98). When the small trial with the largest estimate of effect (Taylor 1980) was excluded, homogenous data still attested to the superior effect of ECT in helping people with schizophrenia to attain global clinical improvement by the end of the course (n=372, 9 RCT, RR 0.76 xed CI 0.63 to 0.92, NNT 7 CI 4 to 20, I-squared 31.3%). Goswami 2001 is the only trial in this comparison to recruit people with clearly dened treatment resistance. Exclusion of this clinically heterogenous data did not signicantly reduce statistical heterogeneity or the signicance of the effect estimate, though the effect of the former on the variability of data remained unsubstantial (n=362, 9 RCT, RR 0.71 random CI 0.54 to 0.94, NNT 5 CI 3 to 10, I-squared 42.6%). The evidence from Sarkar 1994, a small trial of ECT (n=30) in people with early symptoms of schizophrenia (less than six months), was equivocal regarding the benet of ECT combined with antipsychotics versus antipsychotics alone, in global improvement in the short to medium term (RR 0.71 xed CI 0.3 to 1.8). There was also a suggestion that ECT resulted in fewer relapses in the short term than sham ECT (n=47, RR xed 0.26 CI 0.03 to 2.2) and a greater likelihood of being discharged from hospital (n=98, RR xed 0.59, CI 0.34 to 1.01), though the data on which these outcomes are based are limited. There is no evidence that this early advantage for ECT is maintained over the medium to long term, as assessed by other measures of symptomatic improvement over a six-month and two year follow up period, though the trend favoured ECT. Again, the data on which these results are based are sparse. Table 1 reports some skewed and difcult to interpret data on global outcomes. 3.1.2 Mental State The moderate advantage of ECT over sham ECT was again evident when symptomatic improvement was assessed with limited data from BPRS scores at the end of the course of ECT (n=52, WMD -6.14, CI -10.01 to -2.27). ECT also resulted in a signicantly faster rate of improvement as assessed by reduction in BPRS scores midway through the course of ECT (n=52, WMD -4.72 CI -8.87 to -0.57). This early advantage of ECT over sham ECT was maintained in the short term (six weeks) after the course of treatment (n=52, WMD -6.38 CI -10.74 to -2.02). The available data
from one small trial (Ukpong 2002) did not show an advantage for ECT plus antipsychotic drugs over sham ECT and antipsychotic drugs in the medium term (n=16, WMD -0.29 CI -3.49 to -2.91). Table 2 reports some skewed and difcult to interpret data on mental state. 3.1.3 Behaviour and social functioning Only one study, May 1968, reported on behaviour and social functioning and suggested that ECT afforded a little improvement for this outcome (n=90, 1 RCT, MD on average score on the Motility Affect Co-operation Communication Scale 4.1 CI -0.4 to 8.6). Miller 1953 reported on within ward employment and no differences in the two groups were apparent (n=30, RR employed on ward 0.95 CI 0.8 to 1.2). Table 3 reports a little more data on employment. 3.1.4 Leaving the study early Homogeneous data from the 12 trials comparing ECT with sham ECT did not suggest that people treated with ECT dropped out of treatment earlier than those treated with sham ECT (n=405, RR xed 0.84 CI 0.57 to 1.24, I-squared 0%). 3.1.5 Adverse effects: memory Very limited data indicated that visual memory declined after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI -23 to -5); the results of verbal memory tests were equivocal. Table 4 and Table 5 report some skewed data for memory tests. 3.1.6 Death One trial reported on mortality over a three-year follow up (May 1968). No deaths were reported in this trial (n=98). 3.2 ECT vs Antipsychotic drugs 3.2.1 Global impression When ECT given without antipsychotics is directly compared to treatment with antipsychotics alone, the pooled dichotomous results strongly favour the medication group (n=175, 3 RCTs, RR xed 2.18 CI 1.3 to 3.6, I-squared 3.6%). Homogenous data also favour antipsychotic drugs over ECT with regard to numbers discharged after treatment (n=135, RCTs, RR xed 1.98 CI 0.97 to 4, I-squared 43.7%). Very limited data indicated that people treated with ECT are less likely to relapse than those treated with antipsychotics (n=32, 1 RCT, RR xed 0.33 CI 0.1 to 0.9). Continuous measures of global improvement from one trial favoured ECT in the short term, though the results were equivocal in the long term. One of our secondary objectives was to evaluate whether the addition of ECT is benecial to those being treated with antipsychotic drugs. There is some data to suggest that the combination results in an increase in the number of those improved at the end of the course of treatment compared to those treated with ECT alone. Seven of the ten trials that contributed data on clinical global improvement in the comparison of ECT and sham ECT/ placebo studied ECT plus antipsychotics against sham ECT plus antipsychotics (Abraham 1987, Brandon 1985, Goswami 2001, Naidoo 1956, Sarita 1998, Sarkar 1994, Taylor 1980). The remaining three did not use antipsychotics in combination with
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ECT or sham ECT/placebo (Brill 1959, May 1968, Small 1982). Analysis of heterogeneous data from these seven trials showed a non-signicant trend favouring the ECT and antipsychotic combination (n=203, RR random 0.76 CI 0.52 to 1.10, I-squared 62.1%). Reducing heterogeneity by removing one visibly outlying trial (Taylor 1980) marginally reduces the uncertainty around the estimate of effect (n=183, 6 RCT, RR 0.81 xed CI 0.66 to 1.00, I-squared 44.6%). Conversely, homogenous data from the three trials (Brill 1959, May 1968, Small 1982) that compared ECT to sham ECT/ placebo that did not use antipsychotics in either arm, fuels the evidence that ECT is more effective than sham ECT in facilitating global clinical improvement (n=189, RR 0.70 xed CI 0.49 to 0.98, NNT 7 CI 4 to 10, I-squared 0%). However, the overlap in the condence limits for the effect estimates in both subgroups does not allow us to provide a denitive answer to this clinically important question. There is a suggestion of effect for the addition of antipsychotics to those receiving ECT from the subgroup analysis, but this is not supported by homogenous data from the three trials (Janakiramiah 1982, Naidoo 1956, Small 1982) that directly compared the combination of ECT and antipsychotics versus antipsychotics alone (n=151, RR 1.15 xed CI 0.73 to 1.82, I-squared 43.4%). 3.2.2 Mental state When participants were treated with ECT alone, mental state was less likely to improve over the medium term than if they were also given antipsychotic drugs (n=94, 1 RCT, MD on Jenkins Scale 2.20 CI -0.4 to 4.75). However, BPRS scores from one trial (Wu 1989), indicate that when antipsychotics were added to ECT, the combination offered signicant advantages over antipsychotics alone after the course of ECT (n=40 MD -3.9 CI -2.3 to -5.5), and suggest that this was maintained over the medium term (n= 40, MD -7.20 CI -0.3 to -14.1). Skewed data in a trial on ECT in people with catatonia (Girish 2003), analysed by repeat measures analysis of variance in the publication, favoured ECT and placebo over sham ECT and risperidone as assessed by the Bush-Francis Catatonia Scale (Table 6). 3.2.3 Behaviour Limited data from one trial indicated that antipsychotics improved nurse rated continuous measures of behaviour more than treatment with ECT alone (n=95, WMD -6.00 CI -2.82 to -9.18). 3.2.4 Leaving the study early As with the comparison with sham ECT, no differences were seen in numbers leaving the study early in the trials that compared ECT to treatment with antipsychotics (n=529, 9 RCT, RR xed 0.99 CI 0.78 to 1.27, I-squared 0%). Similar numbers remained in the trial May 1968, ve years after treatment with ECT or antipsychotics. However by this time, 73% of the people in both arms were lost to follow up. 3.2.5 Adverse effects Data from a small trial (n=40) that was assessed for subjective and objective evidence of memory impairment failed to nd signi-
cant differences between treatment with ECT or antipsychotics (Bagadia 1981). However, on objective testing, an equally small Chinese trial (n=40) (Wu 1989) detected greater memory impairment after a course of ECT combined with antipsychotics than with antipsychotics alone (n=20, MD serial numbers and picture recall -4.90 CI -0. 8 to -9). However, when re-tested nine weeks later, memory functions had improved in both groups and no signicant differences were detected. Limited data (n=52, Bagadia 1981, Girish 2003) suggests that ECT given without antipsychotics does not result in the occurrence of extrapyramidal side effects compared to treatment with antipsychotic drugs (RR 0.09 xed CI 0.01 to 0.69, I-squared 0%). Treatment with ECT, or antipsychotics with sham ECT, did not differ in the frequency of reporting of a variety of other adverse effects, but again data were limited (n=38, Bagadia 1981). 3.2.6 Death One patient who had not received ECT died within the three-year follow up by May 1968 (n=149, 1 RCT, RR 0.63 CI 0.03 to 15). 3.3 ECT versus psychodynamic-psychotherapy alone or with antipsychotic drugs Limited data from one study comparing ECT with individual psychoanalytic psychotherapy (May 1968) showed a consistent, though non-signicant, trend favouring ECT (both short term and two years later) on several outcomes. When antipsychotics were added to psychoanalytic psychotherapy however, a signicant advantage of the drug group over ECT is seen in the short term (n=90, WMD -5.0 CI -0.54 to -9.46) with a continuing trend two years later. Table 7 and Table 8 present limited data on employment. Skewed data on employment are presented in Table 7 and Table 8 3.4 ECT versus insulin coma therapy It is unclear if insulin coma treatment is used in present day treatment anywhere in the world. This review provides limited evidence that, when ECT is compared with insulin induced coma, the results are equivocal (n=33, 1 RCT, RR not improved at end of course of ECT 0.7 CI 0.3 to 1.8). 3.5 Continuation ECT versus antipsychotics The data for this comparison comes from a single trial ( Chanpattana 1999a) that compared continuation ECT alone with antipsychotics, with continuation ECT added to antipsychotics, for people with treatment resistant schizophrenia. 3.5.1 Global impression When CECT was compared with antipsychotics, the results at the end of the six-month trial, when measured on the GAF scale were equivocal (n=30, 1 RCT, MD -1.24 CI -6.4 to 3.9). However, when CECT was added to antipsychotic drugs, the combination was clearly superior to the use of antipsychotics alone (n= 30, WMD 19.1 CI 9.7 to 28.5), or CECT alone (n=30, WMD 20.3 CI -11.5 to -29.1). Equal numbers (14/15) of people on CECT alone or antipsychotics alone relapsed over the six-month trial period. The addition of CECT to antipsychotic drugs, however, was clearly bene15
cial in reducing relapses compared with antipsychotics alone or CECT alone (n=30, RR xed 0.43 CI 0.23 to 0.81, NNT 2 CI 1.5 to 2.5). 3.5.2 Mental state Similarly, at six months, CECT was no better than treatment with antipsychotic drugs in reducing BPRS scores, though the combination of CECT and antipsychotics was superior to CECT alone (n=30, WMD 18.6 CI 8.6 to 27.6), or antipsychotics alone (n= 30, WMD -19.8 CI -10.3 to 29.2). 3.5.3 Leaving the study early Few people (6/45) left this study early (Chanpattana 1999a), with no clear pattern emerging to suggest a trend in favour of any of the three comparisons. 3.5.4 Adverse effects No signicant differences were seen in cognitive impairment scores between those treated for six months with CECT or antipsychotics. CECT added to antipsychotics resulted in non-signicant trends favouring antipsychotic drugs used alone and the combination versus CECT used alone. 3.6 Electrode placement: unilateral versus bilateral ECT Neither unilateral nor bilateral ECT was superior in terms of global improvement (n=78, 2 RCTs, RR not improved at end of course of ECT 0.79 CI 0.5 to 1.4). There were also no clear differences for outcomes of changes in mental state (Table 9) or cognitive functions (Table 10) over the course of ECT and in the medium term from the limited data from three trials (total n=118). 3.7 ECT dose: threshold stimulus versus suprathreshold stimulus intensities The data for this comparison comes from one trial (Chanpattana 2000, n=64). People with treatment resistant schizophrenia were administered variable numbers of ECT at stimulus intensities just above the seizure threshold (T), twice the seizure threshold (2T), or four times the seizure threshold (4T). Endpoint average scores for global impression (GAF), mental state (BPRS), and cognitive function (MMSE) were not extractable, but we hope to obtain further details on these measures for future updates of this review. 3.7.1 Global impression The three stimulus doses did not differ in numbers improved at the end of the course of ECT (~50% in each group). 3.7.2 Leaving the study early Only ve out of 67 people left this study before completion, with no clear trend favouring any one group. 3.7.3 Number and days of ECT treatments In the subgroup of people given ECT who met the criteria for remission (n=22, 34% of sample), those given ECT at twice the threshold required fewer doses of ECT to attain remission, than those given threshold doses (WMD 6.1 CI 2.4 to 10). Similarly those given 4T required fewer treatments than those treated at threshold doses (WMD 9.4 CI 6.3 to 12.5). Treatment at 4T was non-signicantly superior to treatment at 2T in reducing the number of treatments required to achieve remission (WMD 3.23 CI 0.8 to 5.6). Similarly, those treated at 2T and 4T required fewer
days to attain remission than those given threshold stimuli, but those treated at 4T required on average fewer days of treatment than those given ECT at 2T (WMD 9.4 CI 2.1 to 16.8). 3.8 ECT frequency: three days perweek versus ve day per/week Limited data from one trial comparing unilateral ECT given three times a week versus ve times a week (n=10, Abrams 1967) had usable data only for adverse effects. Average endpoint scores on the results of neuropsychological testing indicated no signicant advantage for the less frequent treatments and none developed clinical evidence of cognitive impairment. 3.9 ECT number of treatments: 12 versus 20 treatments Limited data from one trial (Baker 1960) showed a signicant advantage for 20 treatments over 12 treatments in numbers globally improved at the end of the ECT course (n=43, RR xed 2.53 CI 1.1 to 5.7). None had concurrent antipsychotics. 4. Sensitivity and sub group analyses Other secondary objectives were to evaluate the possibility that ECT may have differential effects in certain subpopulations of people with schizophrenia or with certain schedules of administration of ECT. 4.1 Diagnostic criteria When studies that used diagnostic criteria to diagnose schizophrenia were evaluated separately, a modest but insignicant advantage of ECT over sham ECT in the numbers improved at the end of the course of treatment was maintained from heterogeneous data from seven trials (n=187, RR random 0.70 CI 0.46 to 1.08, Isquared 63%). A signicant advantage for ECT for this outcome was more evident when the three trials that did not use operational denitions of schizophrenia (Brill 1959, May 1968, Naidoo 1956) were separately analysed (n=205, RR xed 0.74 CI 0.57 to 0.98, Isquared 0%). The degree of overlap in the condence intervals of these comparisons, however, indicates that the rigour with which the diagnosis of schizophrenia was made did not signicantly affect the outcome with ECT. 4.2 Subtypes of schizophrenia and symptom prole ECT did not have signicant benecial effects in people with chronic catatonic schizophrenia who took part in the trial by Miller 1953, although this nding could equally be attributed to chronicity rather than the subtype of schizophrenia. Skewed data from one small trial (n=14, Girish 2003), comparing ECT and placebo with risperidone in people with catatonic schizophrenia of varying duration of illness, were analysed by the trialists with repeat measures analysis of variance. This data suggest that ECT produces a faster improvement than risperidone, although dichotomous data of global improvement were equivocal. ECT did signicantly result in clinical improvement by the end of the course for those people diagnosed to have paranoid schizophrenia in the study by Taylor 1980 (n=20, RR xed 0.74, CI 0.6 to 0.91). It was not possible to separate the inuence of the duration of illness from the symptom prole of the participants in the selected trials to assess whether ECT has differential effects on positive or negative symptoms. The trials that favoured ECT
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(Chanpattana 1999a, Chanpattana 2000, May 1968, Taylor 1980, Brandon 1985, Abraham 1987, Wu 1989) reported a benecial effect on positive symptoms. These trials included participants with varying durations of illness. The trial by Chanpattana 1999a on people with treatment resistant schizophrenia provided data on symptom clusters on BPRS, in those responding to ECT prior to randomisation to continuation treatments. These data indicate signicant reductions in positive and negative symptoms, as well as depressive and aggressive symptoms. None of the identied trials assessed the effects of ECT in people with postpartum exacerbations of schizophrenia. 4.3 Duration of illness The power of this review to detect a differential response to ECT for those with a short duration of illness (less than two years) as opposed to those with chronic schizophrenia is very limited. Six trials restricted inclusion to participants with durations of illness less than two years (Abraham 1987, Abrams 1967, Agarwal 1985, Doongaji 1973, Janakiramiah 1981, Sarkar 1994). Two of these (Abraham 1987, Agarwal 1985) provided the data used in the comparison of mental state assessment. This demonstrated a signicant advantage for an ECT/antipsychotic drug combination over sham ECT and antipsychotics in both the rate of clinical improvement and the degree of improvement at the end of the course and in the short term. The participants in the trial by Sarkar 1994 were acutely ill with onset of symptoms less than two months before commencement of treatment. This trial found the combination of ECT and antipsychotics provided no additional benet to treatment with antipsychotics (and sham ECT) in terms of the numbers improved at the end of the course of ECT, or in the short to medium term. The trials by Brill 1959 and Miller 1953 included people with chronic schizophrenia. ECT alone did not result in greater clinical improvement than sham ECT by the end of treatment in these trials. Chanpattana 1999a and Chanpattana 2000 included participants who had been ill from between 3 and 30 years and duration of illness did not signicantly alter outcome. The remainder of the selected trials were heterogeneous for illness duration, thus preventing their inclusion in the evaluation of the effect of this variable on ECT response. 4.4 Number of ECT treatments The only included trial that directly compared differing numbers of ECT treatments (Baker 1960) provided limited evidence that courses of ECT comprising 20 treatments resulted in greater numbers of people showing global clinical improvement than among those given 12 treatments. An earlier trial (Baker 1958) comparing xed courses of 20 treatments without antipsychotics, did not result in greater numbers improved than those given antipsychotic drugs. However, both trials used the ectonus technique to elicit seizures and did not use concurrent antipsychotic drugs. The relevance of these trials to current clinical practice is questionable. Taylor 1980, Brandon 1985 and Abraham 1987 provide evidence that courses of ECT comprising up to 12 treatments, when given with antipsychotics, may be sufcient to result in signicant clini-
cal improvement in people not clearly treatment resistant, but who had shown a limited improvement with antipsychotics compared with antipsychotics and sham ECT (n=67, RR xed 0.30 CI 0.16 to 0.55, I-squared 11%). Limited evidence for people with short duration illness (< two months; Sarkar 1994) clearly indicates that shorter courses of six treatments added to antipsychotics result in equal numbers improved when compared to antipsychotic medication and sham ECT. One trial (Wu 1989) added to the evidence that courses of ECT ranging from six to ten treatments, when combined with moderate doses of antipsychotics, resulted in greater improvement in mental state than treatment with similar doses of antipsychotics alone, after ECT and maintained in the medium term. We did not select any trial for inclusion that studied people treated with courses of ECT greater than 20 treatments versus less than 20 treatments. 5. Small trial or publication bias Funnel plot asymmetry for the ten trials that provided data for the dichotomous outcome not improved, in the comparison of ECT versus sham ECT, raised the possibility that smaller negative trials may exist that have not been published. However, no asymmetry was evident when the funnel plot for the thirteen trials that contributed data for the outcome leaving the study early in the same comparison was examined. There were too few studies for the individual outcomes in the other comparisons to be evaluated for publication bias.
DISCUSSION
1. Strengths and weakness of the review Since the original version of this review was published in 1997 in which we concluded that, In spite of more than ve decades of widespread clinical use, the administration of ECT for those with schizophrenia lacks a strong research base, we have included fourteen more trials, six of which have been conducted since the initial publication of the review. Though the research base for using ECT for people with schizophrenia is expanding in light of continued clinician interest in its use for this group of people, at least in low and middle income countries, there is still a lack of good quality trials for some participants, comparisons and outcomes. This is most notable for the use of ECT for postpartum exacerbation of schizophrenia, maintenance ECT in schizophrenia, and the relative efcacy of ECT versus atypical antipsychotics. Even the number of well-conducted trials comparing ECT with conventional antipsychotics is minimal. The conclusions made in this review are also weakened by the limited data available for some outcomes and comparisons. The former is partly due to poor reporting that rendered data unusable. With the help of trialists, we have been able to recover some valuable data that permits less tentative conclusions for the outcomes
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of some comparisons that were previously not possible. However, some data do rest on assumptions of global improvement derived from other data and not directly rated prospectively using the CGI. The simplicity and robustness of the measure does lend itself to such interpretations, but the reliability of such assumptions remains untested. Additionally, the limitations posed (even when reported data are adequate) by the exclusion of skewed data in metaanalyses, unless individual data are available for all studies to be included in the outcomes of interest, still remain. This limits the inclusion of data for primary outcomes from some good quality trials. Trials in this review spanned ve decades, and it is not surprising that there was considerable variation in research design, trial quality, quality of reporting, and methods of administering ECT. The major strength of this review continues to be that it is a maintained quantitative overview of this topic, with all the advantages and limitations of such an endeavour. 2. Applicability of results This review uses data from trials conducted in eight countries on four continents (Africa, Asia, Europe and North America), with the majority of the trials originating in two Asian countries, India and Thailand. There was no clear pattern differentiating trials among countries with different levels of income. Our search did not nd any trial in which the effects of ECT were studied in people diagnosed to have chronic non-affective mental disorder, though Wu 1988 included participants with unspecied psychosis. None of the trials included people with schizoaffective disorder, except Brill 1959, and in this trial it was not possible to separate out the data from a group of depressed and schizoaffective participants so we had to exclude it from our analysis. The results of this review are subsequently most directly relevant to the use of ECT for adults with schizophrenia, with some relevance to people with schizophreniform disorder and unspecied psychosis. The diagnosis of schizophrenia was based on operational criteria in over half the studies, and depended on clinical judgement in just less than half of the trials. We suggest therefore, that the results of this review are applicable to people with schizophrenia commonly encountered in clinical practice. 3. Homogeneity In spite of considerable clinical heterogeneity in the included trials, the comparisons revealed little statistical heterogeneity barring the outcome numbers not improved for the comparison of ECT versus sham ECT. However, the introduction of a measure to quantify the impact of inconsistency in meta-analyses permits us to retain all ten trials in deriving pooled estimates of effect for this outcome. As a result we are now able to provide clearer guidance on this key outcome compared to earlier versions of this review. 4. Comparisons 4.1 ECT versus Sham ECT
Within the acknowledged limitations, the existing data suggests that ECT may be better than sham ECT/placebo in the short term across different outcomes. This advantage is statistically signicant for the relatively crude (though pragmatic and arguably the most clinically relevant) outcome for which the most data is available (n=382, numbers improved/ not improved at the end of the course of ECT). Though there is some heterogeneity, this appears to contribute less to the variability in the outcome estimates across studies than that attributable to sampling error (chance). The results of consecutive sensitivity analyses, wherein removal of data from a small, but very favourable study (Taylor 1980) and from the one trial that studied people with stringently dened treatment resistant schizophrenia (Goswami 2001), did not result in the pooled estimate favouring those given ECT losing its significant advantage over those given sham ECT. This strengthens the evidence for the use of ECT in people with schizophrenia. The pooled results from the other sensitivity analysis of the three trials that compared ECT with sham ECT/placebo without the use of antipsychotics (Brill 1959, May 1968, Small 1982), suggests that true differences in estimates of effect favouring ECT over sham ECT may be obscured in trials by co-intervention with antipsychotics, which are un-disputably effective in improving the symptoms of schizophrenia. However the quality of reporting and allocation concealment of many included studies was relatively poor, and this has been shown to be associated with over estimates of effect in meta-analyses (Moher 1998). Such problems are quite common in schizophrenia research (Thornley 1998). This advantage of ECT appears largely to lie in a more rapid improvement in symptoms, but there is insufcient evidence to indicate that this advantage over sham ECT, with or without concurrent antipsychotics, persists beyond the initial six to eight weeks. However, this is similar to the effect of ECT in the treatment of depressive disorders, where ECT is recommended for short term improvement in acute symptoms (APA 2001, NICE 2003) and relapse rates are high without appropriate continuation treatment with medication and psychosocial interventions (Devanand 1991, Prien 1986, Prudic 1990, Sackeim 1990). This advantage for ECT is only for people who are later on in the course of their illness, where antipsychotic drugs with sham ECT appear at least as effective. Nor do the results apply to people with stringently dened treatment resistance, where the results for not improved were equivocal. However, both these assertions are weakened by the small sample sizes of representative participants. There was also a suggestion that ECT is superior to sham ECT in facilitating discharges and reducing relapses in the medium term relative to sham ECT. Since there is now more compelling evidence to support the positive effects of ECT in the treatment of schizophrenia, there is justication for large, well designed trials with clear cut outcomes of clinical relevance, of which dichotomous measures of global clinical improvement appear the most widely used by clinicians and
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consumers. In view of the doubts raised regarding the dubious ethical status of sham ECT (given the potential risks with anaesthesia and the possibility that recipients may be misled into thinking that it is risk-free (Lock 1995b)), together with the evidence contained in this review, it would appear that further trials of ECT versus sham ECT without concurrent antipsychotics are unjustied. 4.2. ECT versus antipsychotic drugs Data from this review suggest that ECT given alone is signicantly less effective than antipsychotic medication across several outcomes, even in the short term. This would seem to support clinical experience. However, the review also contains some evidence to support the impression that a faster and greater symptomatic improvement in mental state occurs when ECT is added to antipsychotic medication. For the outcome of global impression there was no clear difference between the combined results of trials using antipsychotics as well as ECT or sham ECT, and those that used no antipsychotic drugs. In one mental state outcome there was a difference, suggesting a possible added benet to combining ECT with antipsychotics. These data are so limited that they should only be considered as hypothesis generating. The results of trials most strongly favouring ECT in the short term (Abraham 1987, Brandon 1985, Taylor 1980, Wu 1989) do suggest a role for the addition of ECT for people who show limited response to antipsychotic medication, but this needs further evaluation. Considering the controversy, there are very few data on adverse effects in general, especially as regards memory loss. One small study failed to detect any (n=40, Bagadia 1981), and another (n= 40, Wu 1989) detected subtle memory impairment after a course of ECT combined with antipsychotics compared to a course of antipsychotics alone, though this disappeared nine weeks later. The clinical impression is that memory impairment is not gross and is transient, though some reports question the validity and perspective of these impressions (Rose 2003). The studies included in this review support clinical impressions but their results should not be considered conclusive. 4.3. ECT versus psychotherapy Very limited data from one trial (May 1968) suggest that, in the short and long term, ECT is better than psychoanalytical psychotherapy for those with schizophrenia, but that adding medication to psychotherapy reverses the trend. This update found no evidence on the relative efcacy of ECT and other psychological treatments such as cognitive behaviour therapy or family interventions in hastening recovery, alleviating persistent symptoms or preventing relapses that might guide opinion or practice 4.4. ECT versus insulin coma therapy
Limited data (n=33, Baker 1958) suggest that insulin coma therapy is as effective, or ineffective as ECT in the short term. If as the above comparisons seem to suggest, ECT does have some effect, this may indicate that even the outmoded insulin coma therapy may have an effect. It is unlikely however that this intervention will receive much research interest. 4.5. Continuation ECT versus antipsychotic drugs Limited evidence from one well-conducted trial (n= 51, Chanpattana 1999a) provides some support for continuation ECT added to antipsychotics. Participants were those who exhitbited clear treatment resistance to conventional antipsychotics. The low number of people required to be treated to prevent a single person relapsing (NNT 2 CI 1.5 to 2.5) is all the more remarkable considering the comparison was not with placebo, but against active treatments, and was amongst a group of people who had exhausted conventional treatment options. Further well conducted studies are required to conrm and elaborate upon these ndings for people with less established treatment resistance, and for those resistant to conventional antipsychotics in receipt of atypical antipsychotics. 4.6 Electrode placement: bilateral versus unilateral ECT The limited data from the three small trials (n=118) contributing to this comparison was further restricted by one of the trials reporting no information for numbers improved or changes in mental state. Data from two trials did not reveal any differences between the two forms of ECT in numbers clinically improved at the end of the course of ECT or in the medium term, or in changes in mental state at the end of the course of ECT. This does not necessarily conrm that the two methods are equal in efcacy. One of the trials (Doongaji 1973) did not use antipsychotics in either arm, and had lower overall rates of improvement than the other (Sarita 1998), where a non-signicant trend marginally favoured bilateral ECT. The results of randomised trials undertaken on people with depression reveal that unilateral ECT needs to be administered at stimulus doses considerably above individually titrated seizure threshold to equal the efcacy of bilateral ECT (Sackeim 1993, Sackeim 2000). Data contained in this review provide evidence that suprathreshold stimuli improve the rate, if not the extent of, improvement with bilateral brief pulse ECT in people with schizophrenia (Chanpattana 2000) and it might transpire that the effects of ECT differ between people with depression and those with schizophrenia. However, because unilateral ECT, at moderately suprathreshold stimulus intensities, is inferior in efcacy but superior to bilateral ECT with regard to cognitive impairment in people with depression (Sackeim 1993), further trials are necessary. These trials for people with schizophrenia would compare unilateral and bilateral ECT with varying doses of electrical stimuli and would hence supplement lower levels of evidence (El Islam 1970). 4.7 Threshold stimulus versus suprathreshold stimulus intensities
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Limited data from a subgroup of people in another well-conducted trial (n=22/64, Chanpattana 2000) attests to faster clinical improvement if ECT is administered at stimulus doses, four times individually titrated seizure threshold, than at lower stimulus doses. Data on such small groups of people are intriguing and should encourage the creation of large studies which would nally resolve the issue of stimulus intensity. 4.8 ECT frequency: three times weekly versus ve times weekly All data are derived from a study size of ten people (Abrams 1967). From this study we cannot draw any conclusions regarding the relative merits and adverse effects of different frequencies of administering ECT. This is another unanswered question regarding ECT that warrants further evidence. (Chanpattana 1999d). 4.9 ECT - number of treatments: short versus long courses The basis of the common assertion that people with schizophrenia require longer courses of ECT than those with depression does not appear to be supported by randomised evidence (n=43, Baker 1960). Some data from other studies not directly comparing length of treatment, do suggest that for those with acute illness, short courses of up to six treatments may sufce, while for people with longer duration of illness, courses of ECT numbering between six and 12, when added to antipsychotic drugs, increase the likelihood of attaining clinical remission. For people with schizophrenia clearly resistant to conventional antipsychotics, however, longer courses of up to 20 treatments with bilateral ECT, administered at four times seizure threshold, could increase the chances of a positive outcome. However data for the number of treatments required for people with treatment resistant schizophrenia is not based on randomised comparisons of short versus long courses of treatment, but on two trials that studied up to 20 treatments with ECT in those with treatment resistant schizophrenia (Chanpattana 1999a, Chanpattana 2000). These two trials used a stabilisation period after obtaining remission with courses of ECT. That period consisted of further ECT spaced at longer intervals over three weeks in order to consolidate remission. Spacing ECT treatments after an initial course of twice or three times weekly treatments is a practice followed by some clinicians, though the evidence for the efcacy of this in people with schizophrenia is limited to uncontrolled case series (Chanpattana 1999b). In view of the results from the two trials in this review that used this practice and longer courses of treatment, together with the speculation in Taylor 1980 that premature termination of treatment after apparent remission may have contributed to relapses, we suggest the need for further trials on the optimal number of treatments and patterns of termination of treatments in people with schizophrenia. 5. Differential effects in subgroups There is no clear evidence to support or refute the use of ECT for particular subgroups of schizophrenia. There is a suggestion
from the primary analysis of limited and skewed continuous data (Table 6) by the trialists in Girish 2003, that people with catatonic schizophrenia who do not show rapid improvement following an initial trial of a benzodiazepine, improve faster with a course of ECT than with the newer antipsychotic risperidone. However resolution of symptoms in some people in this subgroup may require more than six applications of ECT. It is ironic that the frequently quoted assertion (APA 1990, APA 2001, Kruger 1995, Lock 1995a, NICE 2003) that catatonia is an important indication for ECT in people with schizophrenia is currently supported by data of the highest level of evidence from a single trial of only 14 participants, eight of whom were given ECT and four of whom were required to continue with ECT beyond the period of the trial. Limited data suggests that ECT does not provide additional benet over antipsychotic drugs for people with schizophrenia whose illness is of very short duration (less than two months, Sarkar 1994) or those hospitalised with chronic illness (10 years or more, Miller 1953, Brill 1959). However, data from some of the trials included in this review suggest that people with exacerbations of symptoms of schizophrenia may respond to ECT irrespective of the duration of illness (Abraham 1987, Chanpattana 2000, Small 1982, Taylor 1980, Wu 1989). The efcacy of ECT, when schizophrenia is diagnosed using operationally dened criteria, indicates a specic effect on schizophrenic symptoms, rather than causing an improvement in those with affective disorder misdiagnosed as schizophrenia. Many people referred for ECT in the trials included in this review had to various extents, failed to respond to treatment with conventional antipsychotics. However, since people in the trials were not stratied before randomisation based on prior response to antipsychotics, this review is unable to report clear data for this population. However, data from the only trial that directly studied the effects of ECT versus sham ECT in people with stringently dened treatment resistant schizophrenia on concurrent antipsychotics, did not support the use of ECT. This is in contrast to the results obtained in phase I of the continuation ECT trial (Chanpattana 1999a) for people with treatment resistant schizophrenia referred for ECT where 58/101 patients treated with ECT met pre-stated criteria for remission after seven to 25 treatments (mean 13.9 SD 4.8). While these results approximate or better those obtained in trials of clozapine in treatment resistant schizophrenia (Kane 1988), the lack of a control group and randomisation limits their strength. We await the results of the ongoing trial of ECT in people with schizophrenia who have exhausted all other established treatment options other than ECT (Petrides 2000). This important trial will still not provide an answer to whether ECT, when added to conventional or newer antipsychotic drugs, would benet those who show an insufcient response to sequential trials of available drugs, but for whom clozapine may not be a viable option. Unfortunately, this is the case with the majority of people
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with treatment resistance in low income countries. 6. Acceptability of ECT None of the included trials directly addressed the acceptability of treatments for people with schizophrenia. However, data from trials that provided numbers for those leaving the trials early did not suggest that those given ECT dropped out earlier than those given antipsychotics or sham ECT/placebo. 7. Adverse effects The use of ECT appears to be associated with greater cognitive impairment at the end of the course of treatment than the use of conventional antipsychotics, but from the data available, this impairment appears to be transient. Limited evidence indicates normalisation of cognitive functions over the medium term after courses of ECT. This review did not nd data to support lower levels of evidence that ECT may have a protective effect on the emergence of extra-pyramidal symptoms (Goswami 1989, Mukherjee 1994) or tardive dyskinesia (Gardos 1980) for people also receiving antipsychotic drugs. 8. Death None of the included trials, barring May 1968, specically reported on mortality after interventions. However, none of the 779 people given ECT from among the included trials were reported to have died during the course of ECT or during the immediate period of follow up. The very few deaths that did occur in these trials do not implicate the course of ECT, and, overall, mortality seems low.
The overall evidence for the effectiveness of ECT suggests that this approach should remain a potential treatment option for people with psychoses. Despite drugs remaining the preferential treatment for schizophrenia, ECT added to antipsychotic drug treatment does have its place. Data could be used to support the use of courses of up to 12 ECT, and for some people up to 20 treatments. There is no evidence to suggest that only those with schizophrenia experiencing depressive or catatonic features will benet from this treatment. Limited evidence suggests that electrical stimulus doses during ECT, two to four times greater than the minimum dose required to elicit a seizure, are likely to increase the rate of recovery and reduce the number and duration of treatments with bilateral ECT. There is also some data to suggest that the use of continuation ECT along with antipsychotics, for those who respond to an initial course of ECT, is superior to continuation treatment with antipsychotics alone or ECT alone in preventing relapses in the medium term. Even if the benet of ECT is short term, this may be of particular relevance in situations where speed of improvement is important. There are no data relating to treatment of women who have become psychotic in the postpartum period. There remain many unanswered questions for this intervention. The use of ECT for people with schizophrenia from within a well-designed randomised trial, non intrusive on routine care, is justied. 3. For policy makers While some of the evidence in this review only points to the effectiveness of ECT for certain outcomes, there is enough data to suggest the inclusion of ECT as an option for the treatment of people with schizophrenia (NNT 6 CI 4 to 12 for clinical global improvement at the end of the course). There is sufcient evidence of effect to justify funding of well designed, pragmatic trials of ECT in people with varying degrees of antipsychotic non-response and for other unanswered questions regarding this treatment. Guidelines for the use of ECT that based their recommendations (at least in part) on the results of earlier versions of this review (NICE 2003), might wish to consider the results of this update when reviewing the evidence for future recommendations. In the light of this update it would seem unfortunate if current guideline recommendations, due to their perceived adherence to evidence based approaches and widespread impact on clinical opinion and practice, outside their intended sphere of inuence, preclude the option of ECT as a treatment. This is especially the case for those who have exhausted other options or who have limited options to begin with.
AUTHORS CONCLUSIONS Implications for practice

1. For people with schizophrenia The evidence in this review suggests that courses of ECT, when added to antipsychotic medication, in the short term, can result in an increase in global improvement for some people with schizophrenia. There are some data indicating a transient and probably slight memory impairment resulting from ECT. There is no suggestion that ECT should be a sole treatment or treatment of rst choice in schizophrenia. Antipsychotic drugs remain the preferential treatment. There is some evidence to suggest that ECT appears to benet some who have shown a limited response to antipsychotic medication. Also, in those who improve with ECT but relapse in spite of continuing on the prescribed antipsychotics, the continuation of ECT, given at longer intervals, together with antipsychotic drugs could reduce the possibility of relapse in the medium term. 2. For clinicians
Implications for research

1. General In agreement with many other reviewers, we suggest that strict adherence to CONSORT recommendations for reporting of trials (Begg 1996, Moher 2001) would greatly increase the usefulness
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of data, avoid redundancy and facilitate the production of more clear results. Making raw data available at the time of publication, possibly on a web site (Hutchon 2001), though not without its problems (Eysenbach 2001), would greatly reduce errors of interpretation while extracting data, prevent exclusion of valuable data and trials from inclusion in meta-analyses, permit log transformation of skewed data and facilitate individual-patient meta-analysis. 2. Specic to ECT for schizophrenia There are still many unanswered questions regarding the efcacy of ECT for people with schizophrenia. The small number of participants in many trials fuels the case for a large, well planned randomised trial of ECT and antipsychotics (conventional and atypical) compared to antipsychotics (with or without sham ECT). This trial would benet from uncomplicated outcome measures such as clinical global improvement in order to conrm the suggestions of efcacy indicated by this review. Other areas of interest are: i. People with schizophrenia who show limited response to conventional and atypical antipsychotics and evaluating suprathreshold electrical stimulus doses ii. Comparisons of long (>=12) versus short (<12) courses of ECT for people with schizophrenia stratied according to prior response to antipsychotic drugs iii. Simple and preferably categorical measures of social and occupational functioning in the medium to long term iv. Assessment of cognitive and other adverse effects, including mortality through suicides or other causes. In particular, assessing the prevalence of tardive dyskinesia and other movement disorders in these populations would answer the question as to whether the use of ECT protects against the emergence of these syndromes through a direct protective effect or by reducing antipsychotic drug requirement
v. Some direct measure of acceptability of the intervention to the participants, perhaps undertaken by a mixed team of proponents and opponents of the use of ECT vi. The efcacy of ECT for mothers with postpartum exacerbations of schizophrenia, where ECT might be given to hasten recovery and reduce antipsychotic drug exposure during breast feeding vii. The benets and risks of adding ECT to newer atypical antipsychotics such as clozapine and risperidone for people who have failed trials of both conventional and newer drugs and have therefore exhausted treatment options viii. The role of continuation and maintenance ECT in preventing relapse of symptoms ix. Comparisons of costs of ECT versus other treatments ix. Comparisons of the efcacy and safety of ECT and other emerging physical treatments such as repetitive transcranial magnetic stimulation (rTMS) for people with schizophrenia with persistent symptoms.
ACKNOWLEDGEMENTS
We remain ever grateful to Rochelle Seifas who co-reviewed the initial version of this work, and without whose participation this review would not have existed. We are grateful for the considerable and continuing support and input provided by the editorial team of the Cochrane Schizophrenia Group, Tessa Grant, Gill Rizzello. We acknowledge Jon Deeks and J Richards for statistical advice. We thank Chittaranjan Andrade, BN Gangadhar, Worrawat Chanpattana, Harold Sackeim, Max Fink, Pamela Taylor, Joyce Small, Utpal Goswami, Unnati Kumar and Girish Kunigiri for help in locating trials and providing unpublished data, and Michael Phillips, Wong Yip Fong and Chan Wai See for help with translation from Chinese.
REFERENCES
References to studies included in this review

Abraham 1987 {published data only} Abraham K, Kulhara P. The efcacy of electroconvulsive therapy in the treatment of schizophrenia. A comparative study. British Journal of Psychiatry 1987;151:1525. Abrams 1967 {published data only} Abrams R. Daily administration of unilateral ECT. American Journal of Psychiatry 1967;124(3):3846.
Agarwal 1985 {published data only} Agarwal AK, Winny GC. The role of ECT phenothiazine combination in schizophrenia. Indian Journal of Psychiatry 1985;27(3):2336. Bagadia 1981 {published data only} Bagadia VN, Abhyankar RR, Doshi J, Pradhan PV, Shah LP. A double blind controlled study of ECT vs chlorpromazine in schizophrenia. Journal of Association of Physicians of India 1983a;31(10):63740. Bagadia VN, Abhyankar RR, Doshi J, Pradhan PV, Shah LP. Report from a WHO collaborative center for
22
psychopharmacology in India. Psychopharmacology Bulletin 1983b;19(3):55060. Bagadia VN, Shah LP, Pradhan PV, Doshi J, Abhyankar RR. Evaluation of cognitive effects of ECT: preliminary observations. Indian Journal of Psychiatry 1981;23(4): 3249. Bagadia 1988 {published data only} Bagadia VN, Abhyankar RR, Pradhan PV, Shah LP. Reevaluation of ECT in schizophrenia: right temporoparietal versus bitemporal electrode placement. Convulsive Therapy 1988;4:21520. Baker 1958 {published data only} Baker A, Game J, Thorpe J. Physical treatment for schizophrenia. British Journal of Psychiatry 1958;104: 8604. Thorpe J, Baker A. The effects of physical treatment on some psychological functions. British Journal of Psychiatry 1958;104:8659. Baker 1960 {published data only} Baker A, Bird G, Lavin N, Thorpe J. ECT in schizophrenia. Journal of Mental Science 1960;106:150611. Brandon 1985 {published data only} Brandon S, Cowley P, McDonald C, Neville P, Palmer R, Wellstood-Eason S. Electroconvulsive therapy: results in depressive illness from the Leicestershire trial. British Medical Journal 1984;288:225. Brandon S, Cowley P, McDonald C, Neville P, Palmer R, Wellstood-Eason S. Leicester ECT trial: results in schizophrenia. British Journal of Psychiatry 1985;146: 17783. Brill 1959 {published data only} Brill NQ, Crumpton E, Eiduson S, Grayson HM, Hellman LI. Predictive and concomitant variables related to improvement with actual and simulated ECT. Archives of General Psychiatry 1959;1:26372. Brill NQ, Crumpton E, Eiduson S, Grayson HM, Hellman LI, Richards RA. An experimental study of the relative effectiveness of various components of electro-convulsive therapy. American Journal of Psychiatry 1959;115:7345. Brill NQ, Crumpton E, Eiduson S, Grayson HM, Hellman LI, Richards RA. Relative effectiveness of various components of electronconvulsive therapy. Archives of Neurology and Psychiatry 1959;81:62735. Brill NQ, Crumpton E, Eiduson S, Grayson HM, Hellman LI, Richards RA, Strassman HD, Unger AA. Investigation of the therapeutic components and various factors associated with improvement with electroconvulsive treatment: A preliminary report. American Journal of Psychiatry 1957; 113:9971008. Eiduson S, Brill NG, Crumpton E. The effect of electroconvulsive therapy on spinal uid constituents. British Journal of Psychiatry 1958;106:6928. Chanpattana 1999a {published and unpublished data} Chanpattana W. ECT in schizophrenia. Journal of the Psychiatric Association of Thailand 1999;44:15670. Chanpattana W, Chakrabhand ML, Sackeim HA, Kitaroonchai W, Kongsakon R, Techakasem P, Buppanharun
W, Tuntirungsee Y, Kirdcharoen N. Continuation ECT in treatment resistant schizophrenia: a controlled study. Journal of ECT 1999;15:17892. [MEDLINE: 1999422524] Chanpattana 2000 {published and unpublished data} Chanpattana W, Chakrabhand ML, Buppanharun W, Sackeim HA. Effects of stimulus intensity on the efcacy of bilateral ECT in schizophrenia: a preliminary study. Biological Psychiatry 2000;48:2228. [MEDLINE: 1920385419] Chanpattana W, Sackeim HA, Techakasem P, Chakrabhand S. ECT in schizophrenia. APA Annual Meeting, May 1520, Washington DC 1999. Doongaji 1973 {published data only} Doongaji D, Jeste D, Saoji N, Kane P, Ravindranath S. Unilateral versus bilateral ECT in schizophrenia. British Journal of Psychiatry 1973;123:739. Girish 2003 {published and unpublished data} Girish K, Gill NS. Electroconvulsive therapy in lorazepam non-responsive catatonia. Indian Journal of Psychiatry. 2003; Vol. 45:S 5. Girish K, Gill NS. Electroconvulsive therapy in lorazepam non-responsive catatonia. Indian Journal of Psychiatry 2003; 45:215. Kunigiri G, Gill NS, Gangadhar BN, Naimmagadda J. Electroconvulsive therapy in lorazepam non-responsive catatonia. XIIth World Congress of Psychiatry; Aug 24-29; Yokohama, Japan. 2002. Goswami 2001 {published data only} Goswami U, Kumar U, Singh B. Efcacy of electro convulsive therapy in treatment resistant schizophrenia syndrome: A double blind study. 53rd Annual Conference of the Indian Psychiatry Society (9th-11th January 2001, Pune) 2001. Janakiramiah 1981 {published data only} Janakiramiah N, Subbakrishna DK. ECT-chlorpromazine combination compared with chlorpromazine only in schizophrenia. Indian Journal of Psychiatry 1981;23:2303. Janakiramiah 1982 {published data only} Janakiramiah N, Channabasavanna SM, NarasimhaMurthy NS. ECT/chlorpromazine combination versus chlorpromazine alone in acutely ill schizophrenic patients. Acta Psychiatrica Scandinavica 1982;66:46470. May 1968 {published data only} May P, Tuma A, Yale C, Potepan P, Dixon W. Schizophrenia - a follow-up study of results of treatment. Archives of General Psychiatry 1976;33(4):4816. May PR. Treatment of schizophrenia. New York, USA: Science House, 1968. May PR, Tuma AH. Treatment of schizophrenia: an experimental study of ve treatment methods. British Journal of Psychiatry 1965;111:50310. May PR, Tuma AH, Dixon WJ. Schizophrenia - a follow-up study of results of treatment. I. Design and other problems. Archives of General Psychiatry 1976;33(4):4748. May PR, Tuma AH, Dixon WJ, Yale C, Thiele DA, Kraude
23
WH. Schizophrenia. A follow-up study of the results of ve forms of treatment. Archives of General Psychiatry 1981;38 (7):77684. May PRA. Psychotherapy and ataraxic drugs in schizophrenia. 131st Annual Meeting of the American Psychiatric Association, Atlanta, Georgia 1978. 1978. [MEDLINE: 1996206627] May PRA. Schizophrenia follow up: a controlled treatment study. Fragment of article from unknown journal 1974;10:55. May PRA, Tuma H, Yale C, Potepan P, Dixon WJ. Schizophrenia - a follow-up study of results of treatment. II. Hospital stay over two to ve years. Archives of General Psychiatry 1976;33:4816. Wyatt RJ. Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin 1991;17:32551. Miller 1953 {published data only} Miller DH, Clancy J, Cumming E. A comparison between unidirectional current nonconvulsive electrical stimulation given with Reiters machine, standard alternating current electroshock (Cerletti method), and pentothal in chronic schizophrenia. American Journal of Psychiatry 1953;109: 61720. Naidoo 1956 {published data only} Naidoo N. The effects of reserpine (serpasil) on the chronic disturbed schizophrenic: a comparative study of rauwola alkaloids and electroconvulsive therapy. Journal of Nervous and Mental Disease 1956;123:113. Sarita 1998 {published and unpublished data} Sarita EP, Janakiramiah N, Ganagadhar BN, Subbakrishna DK, Rao KMJ. Efcacy of combined ECT after two weeks of neuroleptics in schizophrenia: A double blind controlled study. NIMHANS Journal 1998;16(4):24351. Sarkar 1994 {published and unpublished data} Sarkar P, Andrade C, Kapur B, Das P, Sivaramakrishna Y, Harihar C, Pandey A, Anand A, Dharmendra MS. An exploratory evaluation of ECT in haloperidol-treated DSMIIIR schizophreniform disorder. Convulsive Therapy 1994; 10(4):2718. Small 1982 {published data only} Small JG, Milstein V, Klapper M, Kellams JJ, Small IF. ECT combined with neuroleptics in the treatment of schizophrenia. Psychopharmacology Bulletin 1982;18:345. Small JG, Milstein V, Klapper M, Kellams JJ, Small IF. ECT combined with neuroleptics in treatment of schizophrenia. NCDEU Annual Meeting, May 26-28th, Key Biscayne, Florida, USA 1981. Taylor 1980 {published data only} Taylor P. ECT and schizophrenia in Great Britain. American Journal of Psychiatry 1981;132:25960. Taylor P, Fleminger JJ. ECT for schizophrenia. Lancet 1980;1(8183):13803. Taylor PJ. Schizophrenia and ECT: a case for change in prescription?. In: Hawton K, Cowan P editor(s). Dilemmas and Difculties in the Management of Psychiatric Patients. Oxford: Oxford University Press, 1990:14355.
Ukpong 2002 {published data only} Ukpong DI, Makanjoula ROA, Morakinyo O. A controlled trial of modied electroconvulsive therapy in schizophrenia in a Nigerian teaching hospital. West African Journal of Medicine 2002;21:23740. Ungvari 1982 {published data only} Ungvari G, Bitter I, Czobor P, Vitrai J, Pethoe B. Zur Rolle der neuroleptischen Hochdosis-Therapie und des Elektroschocks bei der Behandlung der akuten Phase von Schizophrenien [The role of the neuroleptic high-dosage therapy and the electroshock in the treatment of the acute phase of schizophrenia]. Psychiatrie Neurologie und Medizinische Psychologie 1981;33(8):45863. Ungvari G, Petho B. High-dose haloperidol therapy: its effectiveness and a comparison with electroconvulsive therapy. Journal of Psychiatric Treatment and Evaluation 1982;4:27983. Wu 1989 {published data only} Wu D, She CW, She CW, Liu CZ, Cho WL, Quon M, Liu SY, Ai SC. Using BPRS and serial numbers and picture recall to test the effectiveness of ECT versus chlorpromazine versus chlorpromazine alone in the treatment of schizophrenia: 40 cases, single blind observations.. Chinese Journal of Nervous and Mental Disorders 1989;15(1):268. [MEDLINE: 1996206627]
References to studies excluded from this review

Aoba 1983 {published data only} Aoba A, Kakita Y, Yamaguchi N, Shido M, Shibata M, Kitani K, Hasegawa K. Electric convulsive therapy (ECT) increases plasma and red blood cell haloperidol neuroleptic activities. Life Sciences 1983;33(18):1797803. [MEDLINE: 1984067019] Arato 1980 {published data only} Arato M, Erdos A, Kurcz M, Vermes I, Fekete M. Studies on the prolactin response induced by electroconvulsive therapy in schizophrenics. Acta Psychiatrica Scandinavica 1980;61 (3):23944. Ayers 1960 {published data only} Ayers CM. The relative value of various somatic therapies in schizophrenia. Journal of Neuropsychiatry 1960;1:15462. Baker 1961 {published data only} Baker AA, Morison M, Game JA, Thorpe JG. Admitting schizophrenic mothers with their babies.. Lancet 1961;2: 2379. Barker 1960 {published data only} Barker JC, Thorpe JG. An evaluation of electroplexy (ECT) techniques. Journal of Mental Science 1960;106: 134760. Benatov 1996 {published data only} Benatov R, Sirota P, Megged S. Neuroleptic-resistant schizophrenia treated with clozapine and ECT. Convulsive Therapy 1996;12:11721. Berg 1959 {published data only} Berg S, Gabriel AR, Impastato DJ. Comparitive evaluation of the safety of chlopromazine and reserpine used in
24
conjunction with ECT. Journal of Neuropsychiatry 1959;1: 1047. Bhatia 1987 {published data only} Bhatia MS, Balkrishna, Dhar NK, Bohra N. Schizophrenia: electrolyte prole & the effect of treatment. Indian Journal of Psychiatry 1987;29:2757. Bhatia 1998 {published data only} Bhatia SC, Bhatia SK, Gupta S. Concurrent administration of clozapine and ECT: a successful therapeutic strategy for a patient with treatment-resistant schizophrenia. Journal of ECT 1998;14:280833. Bowes 1956 {published data only} Bowes HA. The ataractic drugs: the present position of chlorpromazine, frenquel, pacatal, and reserpine in the psychiatric hospital. American Journal of Psychiatry 1956; 113:5309. Brewer 1972 {published data only} Brewer CL, Davidson JR, Hereward S. (ketalar): a safer anaesthetic for ECT.. British Journal of Psychiatry 1972;120: 67980. Chanpattana 1997 {published data only} Chanpattana W. Continuation electroconvulsive therapy in schizophrenia: A pilot study. Journal of the Medical Association of Thailand 1997;80:3117. Chanpattana 1998 {published data only} Chanpattana W. Maintenance ECT in schizophrenia. ACT 6th Annual Meeting, 1996 May 5th, New York, USA 1996. Chanpattana W. Maintenance ECT in schizophrenia. Xth World Congress of Psychiatry 1996, August 27th, Madrid, Spain 1996. Chanpattana W. Maintenance ECT in schizophrenia: A pilot study. Journal of the Medical Association of Thailand 1998;81:1723. Chanpattana 1999b {published and unpublished data} Chanpattana W, Chakrabhand ML, Kirdcharoen N, Tuntirungsee Y, Techakasem P, Prasertsuk Y. The use of the stabilization period in electroconvulsive therapy research in schizophrenia: II. Implementation. Journal of the Medical Association of Thailand 1999;82(6):55868. [MEDLINE: 19**********] Chanpattana 1999c {published data only} Chanpattana W, Chakrabhand MLS, Kongsakon R, Techakasem P, Buppanharun W. Short-term effect of combined ECT and neuroleptic therapy in treatment resistant schizophrenia. Journal of ECT 1997;15:12939. Chanpattana 1999d {published data only} Chanpattana W, Kitaroonchai W, Prasertsuk Y, Chakrabhand MLS, Choovanichvong S. Effects of twice versus thrice weekly electroconvulsive therapy in schizophrenia. Journal of the Medical Association of Thailand 1999;82:47782. Chanpattana 1999e {published and unpublished data} Chanpattana W. ECT in Schizophrenia. Journal of the Psychiatric Association of Thailand 1999;44:15670. Chanpattana W, Sackeim HA, Techakasem P, Chakrabhand S. ECT in schizophrenia. 152nd Annual Meeting of the
American Psychiatric Association. Washington DC, USA. 15-20th May. 1999. Chanpattana 2000b {published data only} Chanpattana W. Maintenance ECT in treatment-resistant schizophrenia. Journal of the Medical Association of Thailand 2000;83:15. Chanpattana 2000c {published data only} Chanpattana W, Techakasem P, Chakrabhand S, Raksakietisak S. Seizure threshold in ECT: I. Initial seizure threshold. Journal of the Medical Association of Thailand 2000;83:17. Chanpattana W, Techakasem P, Chakrabhand S, Raksakietisak S. Seizure threshold in ECT: II: Dose titration vs age and half age methods. Journal of the Medical Association of Thailand 2000;83:27882. Chanpattana 2002 {unpublished data only} Chanpattana W, Buppanharun W, Chakrabhand MLS. Seizure Threshold in Electroconvulsive Therapy: Differences between Instruments. 155th Annual Meeting of the American Psychiatric Association; 2002 May 1823rd; Philadelphia, PA, USA. 2002. Chatterjee 1980 {published data only} Chatterjee SB, Mohammed E. Evaluation of unilateral electro-convulsive therapy (a double blind study). Indian Journal of Psychiatry 1980;22:18594. Childers 1961 {published data only} Childers RT, Therrien R. A comparison of the effectiveness of triuoperazine and chlorpromazine in schizophrenia. American Journal of Psychiatry 1961;118:5524. Childers 1964 {published data only} Childers RT. Comparison of four regimes in newly admitted female schizophrenics. American Journal of Psychiatry 1964; 120:10101. Cronholm 1961 {published data only} Cronholm B, Molander L. Memory disturbances after ECT. Acta Psychiatrica et Neurologica Scandinavica. 1961;36: 8390. dElia 1970 {published data only} dElia G. Comparison of ECT with unilateral and bilateral stimulation. V. Confusion and other side-effects. Acta Psychiatrica Scandinavica Supplementum 1970;215:7689. d Elia G. Comparison of ECT with unilateral and bilateral stimulation. IV. Retrograde amnesia. Acta Psychiatrica Scandinavica Supplementum 1970;215:6175. dElia G, Perris C. Comparison of ECT with unilateral and bilateral stimulation: I. Seizure and post-seizure electroencephalographic pattern. Acta Psychiatrica Scandinavica Supplementum 1970;215:929. Das 1991 {published data only} Das PS, Saxena S, Mohan D, Sundaram KR. Adjunctive electroconvulsive therapy for schizophrenia. National Medical Journal of India 1991;4:1834. Delva 1996 {published data only} Nicholas JD, Jame SL, Martin R, Rita MK, James I, Dennis WL, John JW. Electrical dose and seizure threshold
25
in bifrontal, bitemporal and right unilateral ECT - relations to clinical and cognitive outcomes. 149th Annual Meeting of the American Psychiatric Association, 1996 1996. Dodwell 1989 {published data only} Dodwell D, Goldberg D. A study of factors associated with response to electroconvulsive therapy in patients with schizophrenic symptoms. British Journal of Psychiatry 1989; 154:6359. Early 1999 {published data only} Early T. Anesthesia as an alternative to ECT for people with severe depression. Stanley Foundation Research Awards - 1999 Research Award Recipients 1999:// www.stanleyresearch.org/ (accessed February 2001). [MEDLINE: 1920385419] El Islam 1970 {published data only} El-Islam MF, Ahmed S, Erfan M. The effect of unilateral ECT on schizophrenic delusions and hallucinations. British Journal of Psychiatry 1970;117:4478. Fink 1958 {published data only} Fink M. Placebo-controlled studies of ECT. British Journal of Psychiatry 1982;141:2134. [MEDLINE: 1983001046] Fink M, Kahn RL, Green MA. Experimental studies of the electroshock process. Diseases of the Nervous System 1958; 19:1138. Frankenberg 1993 {published data only} Frankenburg FR, Suppes T, McLean PE. Combined clozapine and electroconvulsive therapy. Convulsive Therapy 1993;9:17680. Friedel 1986 {published data only} Friedel RO. The combined use of neuroleptics and ECT in drug-resistant scizophrenic patients. Psychopharmacology Bulletin 1986;22:92830. Gambill 1966 {published data only} Gambill JM, Wilson IC. Activation of chronic withdrawn schizophrenics. Diseases of the Nervous System 1966;27: 6157. Gander 1967 {published data only} Gander DR, Bennett PJ, Kelly DH. Hexauorodiethyl ether (indoklon) convulsive therapy: a pilot study. British Journal of Psychiatry 1967;113:11438. Gang 1997 {published data only} Gang Z, Shu Bai J, Liang Dong Z. Comparative clinical study on the treatment of schizophrenia with electroacupuncture and reduced doses of antipsychotic drugs. American Journal of Acupuncture 1997;25:2531. Gangadhar 2000 {published data only} Gangadhar BN, Mayur PM, Janakiramaiah N, Subbakrishna DK, Rao GS. Cardiovascular response during ECT: a crossover study across stimulus conditions. Journal of ECT 2000; 16:17782. Geretsegger 1998 {published data only} Geretsegger C, Rochowanski E, Kartnig C, Unterrainer AF. Propofol and methohexital as anaesthetic agents for electroconvulsive therapy (ECT): a comparison of seizure quality measures and vital signs. Journal of ECT 1998;14 (1):2835. [MEDLINE: 19**********]
Goller 1960 {published data only} Goller ES. A controlled trial of reserpine in chronic schizophrenia. British Journal of Psychiatry 1960;106: 140812. Gottlieb 1951 {published data only} Gottlieb JS, Huston PE. Treatment of schizophrenia. A comparision of three methods: brief psychotherapy, insulin coma and electric shock. Journal of Nervous and Mental Diseases 1951;113:23746. Green 1994 {published data only} Green AI, Zalma A, Berman I, DuRand CJ, Salzman C. Clozapine following ECT: a two-step treatment. Journal of Clinical Psychiatry 1994;55:38890. Greenblatt 1962 {published data only} Greenblatt M, Grosser GH, Wechsler H. A comparative study of selected antidepressant medications and EST. American Journal of Psychiatry. 1962;119:14453. Gujavarty 1987 {published data only} Gujavarty K, Greengerg LB, Fink M. Electroconvulsive therapy and neuroleptic medication in therapy resistant positive-symptom psychosis. Convulsive Therapy 1987;3: 18595. Guo 2000 {published data only} Guo J, Xu G, Huang X. An analysis on 100 psychotic patients treated with modied electroconvulsive therapy. Sichuan Mental Health 2000;3:202. Hargreaves 1972 {published data only} Hargreaves WA, Fischer A, Elashoff M, Blacker KH. Delayed onset of impairment following electrically induced convulsions. Acta Psychiatrica Scandinavicia 1972;48: 6977. He 2001 {published data only} He Q, Lui B, Qin Q, et al.A comparative study of side effects of non-versus dominance ect on schizophrenics with EEG and ECG monitoring. Acta Academiae Medicinae Shandong 2001;39:4850. Heath 1964 {published data only} Heath E, Adams A, Wakeling P. Short courses of ECT and simulated ECT in chronic schizophrenia. British Journal of Psychiatry 1964;110:8007. Hirose 2001 {published data only} Hirose S, Ashby CR, Mills MJ. Effectiveness of ECT combined with risperidone against aggression in schizophrenia. Journal of ECT 2001;17:226. Hrebicek 1965 {published data only} Hrebicek S, Kumpel Q, Sokol I, Topiar A, Grumlik R, Uhlir F. Comparison of effects of classical and combined therapy in schizophrenia. Activitas Nervosa Superior 1965;7 (3):2434. Ikeji 1999 {published data only} Ikeji OC, Ohaeri JU, Osahon RO, Agidee RO. Naturalistic comparative study of outcome and cognitive effects of unmodied electro-convulsive therapy in schizophrenia, mania and severe depression in Nigeria. East African Medical Journal 1999;76:64450.
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James 1999 {published data only} James DV, Gray NS. Elective combined electroconvulsive and clozapine therapy. International Clinical Psychopharmacology 1999;14:6972. Jiang 1989 {published data only} Jiang ZN. Role of electroconvulsive therapy in treating schizophrenia. Chung Hua Shen Ching Chong Shen KO Tsa Chih 1989;22(2):668. Johnson 1960 {published data only} Johnson LC, Ulett GA, Johnson M, Smith K, Sines JO. Electroconvulsive therapy (with and without atropine). Effect on electronically analyzed electroencephalogram. Archives of General Psychiatry 1960;2:32436. Johnstone 1997 {published data only} Johnstone EC, Owens DGC. Does early treatment have an effect on outcome?. 10th Congress of the European College of Neuropsychopharmacology, 1997, Vienna, Austria. 1997. Kellner 1999 {published data only} Kellner CH, Bernstein H, Rummans TA, Husain MM, Petrides G, Beale MD, Zhao W, Rush AJ, Fink M, Knapp R. Acute ECT response: ndings from the consortium for research in ECT trial. 152nd Annual Meeting of the American Psychiatric Association; 1999 May 15-20th, Washington DC, USA. 1999. [MEDLINE: 19**********] King 1958 {published data only} King PD. Regressive EST, chlorpromazine, and group therapy in treatment of hospitalized chronic schizophrenics. American Journal of Psychiatry 1958;115:3547. King 1959 {published data only} King PD. A comparison of REST and ECT in the treatment of schizophrenics. American Journal of Psychiatry 1959;116:3589. King 1960 {published data only} King PD. Chlorpromazine and electronconvulsive therapy in the treatment of newly hospitalized schizophrenics. Journal of Clinical and Experimental Psychopathology 1960; 21:1015. Klapheke 1999 {published data only} Klapheke MM. Clozapine, ECT, and schizoaffective disorder, bipolar type. Convulsive Therapy 1991;7(1):369. Klapheke MM. Follow-up on Clozapine and ECT. Convulsive Therapy 1991;7:3035. Konig 1990 {published data only} Konig P, Glatter-Gotz U. Combined electroconvulsive and neuroleptic therapy in schizophrenia refractory to neuroleptics. Schizophrenia Research 1990;3:3514. Krystal 1993 {published data only} Krystal AD, Weiner RD, McCall W, Shelp FE, et al.The effects of ECT stimulus dose and electrode placement on the ictal electroencephalogram: An intraindividual crossover study. Biological Psychiatry 1993;34(11):75967. Kupchik 2000 {published data only} Kupchik M, Spivak B, Mester R, Reznik I, Gonen N, Weizman A, Kotler M. Combined electroconvulsive-
clozapine therapy. Clinical Neuropharmacology 2000;23: 146. Landy 1991 {published data only} Landy DA. Combined use of clozapine and electroconvulsive therapy. Convulsive Therapy 1991;7:21821. Langsley 1959 {published data only} Langsley DG, Enterline JD, Hickerson GX. A comparison of chlorpromazine and EST in treatment of acute schizophrenic and manic reactions. Archives of Nuerology and Psychiatry 1959;81:38491. Laurell 1970a {published data only} Laurell B//Perris C. Comparison of ECT and ICT. I. Seizure and post-seizure electroencephalographic pattern. Acta Psychiatrica Scandinavica Supplementum 1970;213:821. [MEDLINE: 1983001046] Laurell 1970b {published data only} Laurell B. Comparison of electric and urothyl convulsive therapy: confusion and other side effects. Acta Psychiatrica Scandinavica Supplementum 1970;213:6173. Laurell B. Comparison of electric and urothyl convulsive therapy: retrograde amnesia. Acta Psychiatrica Scandinavica Supplementum 1970;213:5160. Levin 1990 {published data only} Levin Y, Salganik I, Etzion T, Levy A, et al.Naloxone fails to improve memory and cognitive disturbances after electroconvulsive treatment. Brain Dysfunction 1990;3(43):1936. Levine 1995 {published data only} Levine J, Pomerantz T, Stier S, Belmaker RH. Lack of effect of 6g inositol treatment of post-ECT cognitive function in humans. Journal of Psychiatric Research 1995;29 (6):4879. [MEDLINE: 1996206627] Levine 1997 {published data only} Levine J. Controlled trials of inositol in psychiatry. 6th World Congress of Biological Psychiatry, 1997 Nice, France. 1997. Lewis 1982 {published data only} Lewis AB. ECT in drug-refractory schophrenics. Hillside Journal of Clinical Psychiatry 1982;4:14154. Li 2002 {published data only} Li F, Yin J, Pang G. Nursing observation on dominant lateral ECT in the treatment of schizophrenia. Hebei Medicine 2002;8:2302. Ligthart 1956 {published data only} Ligthart PWK, Johnston RP, Sussman E. Evaluation of combined coramine-electroshock therapy in the treatment of schizophrenia. American Journal of Psychiatry 1956;112: 61923. Lingl 1964 {published data only} Lingl FA. Combined drug therapy compared with electric shock in psychotic depressions. American Journal of Psychiatry 1964;120:80810. Lui 1993 {published data only} Lui PW, Ma JY, Chan KK. Modication of tonic clonic convulsions by atracurium in multiple monitored
27
electroconvulsive therapy. Journal of Clinical Anesthesia 1993;5(1):1621. McInnes 1972 {published data only} McInnes EJ//James NM. A comparison of ketamine and methohexital in electroconvulsive therapy. Medical Journal of Australia 1972;1(20):10312. Meyendorf 1981 {published data only} Meyendorf R. Electroconvulsive therapy in endogenous psychoses. Munchener Medizinische Wochenschriftenschrift 1981;123(19):8002. [MEDLINE: 1981197463] Mezquita 1973 {published data only} Mezquita Blanco J, Cubillo Sanchez J, Laforgue J, de Enterria G, Rey Gonzalez A. Side and therapeutic effects of bilateral and unilateral electroconvulsive therapy. Archivos de Neurobiologia 1973;36(2):10528. Milstein 1990 {published data only} Milstein V, Small JG, Miller MJ, Sharpley PH, Small IF. Mechanisms of action of ECT: schizophrenia and schizoaffective disorder. Biological Psychiatry 1990;27: 128292. Murillo 1973 {published data only} Exner JE Jr, Murillo LG. A long term follow-up of schizophrenics treated with regressive ECT. Diseases of the Nervous System 1977;38:1628. Exner JE Jr, Murillo LG. Effectiveness of regressive ECT with process schizophrenia. Diseases of the Nervous System 1973;34:448. Murillo LG, Exner JE. A controlled study on the value of regressive electroplexy in schizophrenia. 5th World Congress of Psychiatry, 1971, Ciudad de Mexico. 1971: 163. Murillo LG, Exner JE Jr. Ataractic drugs versus ECT in schizophrenia. American Journal of Psychiatry 1973;130: 11623. Murillo LG, Exner JE Jr. The effect of regressive ECT with process schizophrenics. American Journal of Psychiatry 1973; 130:26973. Natani 1983 {published data only} Natani GD, Gautam S, Gehlot PS. Comparison on three treatment regimes in schizophrenia. Indian Journal of Psychiatry 1983;25:30611. Ostzovscki 1997 {published data only} Ostzovascki H, Mosolew S. Intensive therapy for attacks of acute schizophrenia. Unknown conference abstract. 1997. Ottosson 1960 {published data only} Ottosson J. Effect of lidocaine on the seizure discharge in electroconvulsive therapy [1-6]. Acta Psychiatrica Scandinavica Supplementum 1960;145(60):732. Petrides 1996 {published data only} Petrides G, Fink M. The half age stimulation strategy for ECT dosing. Convulsive Therapy 1996;12:13846. Peyman 1956 {published data only} Peyman DAR. An investigation of the effects of group psychotherapy on chronic schizophrenic patients. Group Psychotherapy 1956;9:359.
Pisvejc 1998 {published data only} Pisvejc J, Hyrman V, Sikora J, Berankova A, Kobeda B, Auerova M, Sochorova V. A comparison of brief and ultrabrief pulse stimuli in unilateral ECT. Journal of ECT 1998;14(2):6875. [MEDLINE: 19**********] Rahman 1968 {published data only} Rahman R. A review of treatment of 176 schizophrenic patients in the mental hospital Pabna. British Journal of Psychiatry 1968;114:7757. Ray 1962 {published data only} Ray SD. Relative efcacy of electroconvulsive therapy and chlorpromazine in schizophrenia. Journal of the Indian Medical Association 1962;38:3323. Reichert 1976 {published data only} Reichert H, Benjamin J, Keegan D, Marjerrison G. Bilateral and non dominant unilateral ECT. I. Therapeutic efcacy. Canadian Psychiatric Association Journal 1976;21(2):6978. Rhode 1961 {published data only} Kelly D, Sargant W. Present treatment of schizophrenia: a controlled follow-up study. British Medical Journal 1965;i: 14759. Rhode P, Sargant W. Treatment of schizophrenia in general hospitals. British Medical Journal 1961;ii:6770. Safferman 1992 {published data only} Safferman AZ, Munne R. Combining clozapine with ECT. Convulsive Therapy 1992;8:1413. Sajatovic 1993 {published data only} Sajatovic M, Meltzer HY. The effect of short-term electroconvulsive treatment plus neuroleptics in treatmentresistant schizophrenia and schizoaffective disorder. Convulsive Therapy 1993;9:16775. Small 1968 {published data only} Small J, Small I, Sharpley P, Moore D. A double-blind comparative evaluation of urothyl and ECT. Archives of General Psychiatry 1968;19(1):7986. Smith 1967 {published data only} Smith K, Surphlis WRP, Gynther MD, et al.ECTchlorpromazine and chlorpromazine compared in the treatment of schizophrenia. Journal of Nervous and Mental Disease 1967;144:28490. Stenback 1957 {published data only} Stenback A, Viitamaki RO, Kukkonen S. Personality changes in electroconvulsive treatment. Acta Psychiatrica et Neurologica Scandinavica 1957;32:34559. Sullivan 1974 {published data only} Sullivan PR. Treatment of acute schizophrenia: the place of ECT. Diseases of the Nervous System 1974;35(10):4679. Swoboda 2001 {published data only} Swoboda E, Conca A, Konig P, Waanders R, Hansen M. Maintenance electroconvulsive therapy in affective and schizoaffective disorder. Neuropsychobiology 2001;43:238. Tang 2003 {published data only} Tang WK, Ungvari GS. Efcacy of electroconvulsive therapy in treatment-resistant schizophrenia: a prospective open
28
trial.. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2003;27:3739. Ulett 1956 {published data only} Ulett GA, Smith K, Gleser GC. Evaluation of convulsive and subconvulsive shock therapies utilising a control group. American Journal of Psychiatry 1956;112:795802. Vojtechovsky 1970 {published data only} Vojtechovsky M. Modication of memory disturbances after electroshock with centrophenoxine [Beeinussung der Gedachtnisstorungen nach Elektroshock mit Centrophenoxin]. Arzneimittel Forschung 1970;20(7): 8824. Weinstein 1971 {published data only} Weinstein MR, Fischer A. Combined treatment with ECT and antipsychotic drugs in schizophrenia. Diseases of the Nervous System 1971;32:8017. Wessels 1972 {published data only} Wessels WH. A comparative study of the efcacy of bilateral and unilateral ECT with thioridazine in acute schizophrenia. 5th World Congress of Psychiatry. 1971: 574. Wessels WH. A comparative study of the efcacy of bilateral and unilateral electroconvulsive therapy with thioridazine in acute schizophrenia. South African Medical Journal 1972;46(26):8902. West 1982 {published data only} West ED, Jackson A, Physentides A, Seenivasagan S, Jezard P, Nicholson A, Ra MR, Knight H. Randomized comparative trial of a ward discussion group. British Journal of Psychiatry 1982;141:7680. Xie 1994 {published data only} Xie G, Zhu X, Chen J. Prolactin and growth hormone serum levels during electroconvulsive therapy in schizophrenics. Chinese Journal of Neurology 1994;3:1602. Xue 1985 {published data only} Chongcheng X, Huansen X, Qingchi R, Yuande C, Dingli L. Electric acupuncture convulsive therapy. Convulsive Therapy 1985;1(4):24251.
Agarwal 1992 Agarwal AK, Andrade C, Reddy MV. The practice of ECT in India: issues relating to the administration of ECT. Indian Journal of Psychiatry 1992;34:28598. Alderson 2004 Alderson P, Green S, Higgins JPT. Cochrane Reviewers Handbook 4.2.2 [updated December 2003]. The Cochrane Library 2004, Issue Issue 1. [: In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd] Altman 1996 Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996;313:1200. Andrade 1988 Andrade C, Gangadhar BN, Subramaniam DK. A double blind comparion of sinusoidal wave and brief pulse electroconvulsive therapy in endogenous depression. Convulsive Therapy 1988;4:297305. Andrade 1993 Andrade C, Agarwal AK, Reddy MV. The practice of ECT in India: II. The practical administration of ECT. Indian Journal of Psychiatry 1993;35:816. Andrade 2002 Andrade C, Kurinji S. Continuation and maintenance ECT: a review of recent research. The Journal of ECT 2002;18: 14958. Andreasen 1982 Andreasen NC. Negative symptoms in schizophrenia: denition and reliability. Archives of General Psychiatry 1982;39:7848. APA 1990 American Psychiatric Association. Task Force on electroconvulsive therapy: recommendations for treatment, training, and privileging. Washington DC, USA: American Psychiatric Press, 1990, 1990. APA 1995 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth. Washington DC, USA: American Psychiatric Association, 1995. APA 2001 American Psychiatric Association. Committee on Electroconvulsive Therapy. The practice of electroconvulsive therapy: recommendations for treatment, training and privileging: a task force report of the American Psychiatric Association. Second Edition. Washington DC, USA: American Psychiatric Association, 2001. Begg 1996 Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, Pitkin R, Rennie D, Schulz KF, Simel D, Stroup DF. Improving the quality of reporting of randomized controlled trials: the CONSORT statement. JAMA 1996;276(8): 6379. Bland 1997 Bland JM. Statistics notes. Trials randomised in clusters. BMJ 1997;315:600.
29
References to studies awaiting assessment

Yao 2000 {published data only} Yao Shaomin, Zhang zhenlan, Luo Suqin. Memory deciency of schizophrenics after non-convulsive ECT therapy. Chinese Mental Health Journal 2000;6:38890.
References to ongoing studies

Petrides 2000 {unpublished data only} Petrides G, Svetina CJ, Malur C, Fink M, Bailine S, Mendelowitz A, Gold J, Kane J, Schooler N. Electroconvulsive Therapy in Clozapine Refractory Schizophrenia. http://www.clinicaltrials.gov/ct/show/ NCT00042224 2002. [: ClinicalTrials.gov Identier: NCT00042224]
Additional references
Burt 2002 Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applications of transcranial magnetic stimulation : a meta analysis. International Journal of Neuropsychopharmacology 2002;5:73103. Bush 1996 Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia. I. Rating scale and standardized examination. Acta Psychiatrica Scandinavica 1996;93:12936. Daskalakis 2002 Daskalakis ZJ, Christensen BK, Fitzgerald PB, Chen R. Transcranial Magnetic Stimulation: a new investigational and treatment tool in psychiatry. The Journal of Neuropsychiatry and Clinical Neurosciences 2002;14:40615. Deeks 2003 Deeks JJ, Higgins, JPT, Altman DG, editors. Analysing and presenting results. In: Alderson P, Green S, Higgins J editor (s). Cochrane Reviewers Handbook 4.2.2 [updated December 2003]. In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd, 2004. Devanand 1991 Devanand DP, Sackeim HA, Prudic J. Electroconvulsive therapy in the treatment resistant patient. Psychiatric Clinics of North America 1991;4:90523. Devanand 1994 Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA. Does ECT alter brain structure?. American Journal of Psychiatry 1994;151:95770. Divine 1992 Divine GW, Brown JT, Frazier LM. The unit of analysis error in studies about physicians patient care behavior. Journal of General Internal Medicine 1992;7(6):6239. Donner 2002 Donner A, Klar N. Issues in the meta-analysis of cluster randomized trials. Statistics in Medicine 2002;21:297180. Ellsworth 1959 Ellsworth RB, Clayton WH. Measurement of improvement in mental illness. Journal of Consulting Psychology 1959;23: 1520. Ende 2000 Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. The hippocampus in patients treated with electroconvulsive therapy : a proton magnetic resonance spectroscopic imaging study. Archives of General Psychiatry 2000;57: 93743. Endicott 1976 Endicott J, Spitzer RL, Fleiss JL. The global assessment scale: a procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 1976;33:76671. Eysenbach 2001 Eysenbach G, Sa E-R. Code of conduct is needed for publishing raw data. BMJ 2001;323:166.
Fink 1991 Fink M. Impact of the antipsychiatry movement on the revival of electroconvulsive therapy in the United States. Psychiatric Clinics of North America 1991;14:793801. Fink 1996 Fink M, Sackeim HA. Convulsive therapy in schizophrenia? . Schizophrenia Bulletin 1996;22:739. Folstein 1975 Folstein NF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 1975;12: 18998. Gardos 1980 Gardos G, Samu I, Kallos M, Cole JO. Absence of severe tardive dyskinesia in Hungarian schizophrenic out-patients. Psychopharmacology (Berlin) 1980;71:2934. Goodnick 2001 Goodnick PJ, Rush AJ, George MS, Marangell LB, Sackeim HA. Vagus nerve stimulation in depression. Expert opinion in pharmacotherapy 2001;2:10613. Goswami 1989 Goswami U, Dutta S, Kuruvilla K, Paap E, Perenyi A. Electroconvulsive therapy in neuroleptic induced parkinsonism. Biological Psychiatry 1989;26:2345. Gulliford 1999 Gulliford MC. Components of variance and intraclass correlations for the design of community-based surveys and intervention studies: data from the Health Survey for England 1994. American Journal of Epidemiology 1999;149: 87683. Guy 1976 Guy W. Early clinical drug evaluation (ECDEU) assessment manual for psychopharmacology. Rockwille MD, USA: US Department of Health, Education and Welfare, 1976. [: Publication ADM 76338] Higgins 2003 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327: 55760. Hutchon 2001 Hutchon DJR. Infopoints: Publishing raw data and real time statistical analysis on e-journals. BMJ 2001;322:530. Jenkins 1959 Jenkins RL, Stauffacher J, Hester R. A symptom rating scale for use with psychotic patients. Archives of General Psychiatry 1959;1:197204. Johns 1995 Johns CA, Thompson JW. Adjunctive treatments in schizophrenia: pharmacotherapies and electroconvulsive therapy. Schizophrenia Bulletin 1995;21:60719. Kane 1988 Kane JM, Honigfeld G, Singer J, Meltzer H, Clozaril Collaborative Study Group. Clozapine for the treatment of treatment-resistant schizophrenia: a double-blind
30
comparison with chlorpromazine. Archives of General Psychiatry 1988;45:78996. Kendell 1981 Kendell R E. The present status of electroconvulsive therapy. British Journal of Psychiatry 1981;139:26583. Khan 1993 Khan A, Mirolo MH, Hughes D, Bierut L. Electroconvulsive therapy. Psychiatric Clinics of North America 1993;16: 497513. Kongsakon 1994 Kongsakon R, Vanichtanom R. Assessment of the differences in MMSE between neurological, psychiatric patients and normal population. Journal of Rajwithi Hospital 1994;5: 99106. Kopell 2004 Kopell BH, Greenberg B, Rezai AR. Deep brain stimulation for psychiatric disorders. Journal of Clinical Neurophysiology 2004;21:5167. Kruger 1995 Kruger RB, Sackeim HA. Electroconvulsive therapy and schizophrenia. In: Hirsch SR, Weinberger D editor(s). Schizophrenia. Oxford: Blackwell, 1995:50345. Langfeldt 1960 Langfeldt G. Diagnosis and prognosis of schizophrenia. Proceedings of the Royal Society of Medicine 1960;53: 104752. Leonhard 1979 Leonhard K. The Classication of Endogenous Psychoses. New York, USA: Irvington, 1979. Lerer 1995 Lerer B, Shapira B, Calev A, Tubi N, Drexler H, Kindler S, Lidsky D, Schwartz JE. Antidepressant and cognitive effects of twice, versus three-times-weekly ECT. American Journal of Psychiatry 1995;152:56470. Lock 1995a Lock T. ECT in schizophrenia. In: Freeman CP editor(s). The ECT Handbook. The Second Report of the Royal College Of Psychiatrists Special Committee on ECT. London: Royal College of Psychiatrists, 1995:810. Lock 1995b Lock T. Non-convulsive electric shock treatment. In: Freeman CP editor(s). The ECT Handbook. The Second Report of the Royal College Of Psychiatrists Special Committee on ECT. London: Royal College of Psychiatrists, 1995: 3132. Lorr 1953 Lorr M. Multidimensional scale for rating psychiatric patient. Veterans Admin Tech Bull 1953:10507. Luborsky 1962 Luborsky L. Clinicians judgments of mental health: a proposed scale. Archives of General Psychiatry 1962;7: 40717. Maletzky 1986 Maletzky BM. Conventional and multiple monitored electroconvulsive therapy. A comparison in major depressive
episodes. Journal of Nervous and Mental Disease 1986;174: 25764. Marder 1993 Marder SR, Ames D, Wirshing WC, Van Putten T. Schizophrenia. Psychiatric Clinics of North America 1993; 16:56787. Marshall 2000 Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. British Journal of Psychiatry 2000;176: 24952. Martin 2002 Martin JLR, Barbanoj MJ, Schlaepfer TE, Clos S, Perez V, Kulisevsky J, Gironell, A. Transcranial magnetic stimulation for treating depression (Cochrane Review). The Cochrane Library 2002, Issue 2.[Art. No.: CD003493. DOI: 10.1002/14651858.CD003493] Martin 2003 Martin JLR, Barbanoj MJ, Prez V, Sacristn M. Transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder (Cochrane Review).. The Cochrane Library 2003, Issue 3. McCall 2004 Mc Call WV, Dunn A, Rosenquist PB. Quality of life and function after electroconvulsive therapy. British Journal of Psychiatry 2004;185:4059. Moher 1998 Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP. Does quality of reports of randomised trials affect estimates of intervention efcacy reported in meta-analyses?. Lancet 1998;352:60913. Moher 2001 Moher D, Schulz KF, Altman D, for the CONSORT group. The CONSORT statement: Revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA 2001;285:198791. Monroe 1991 Monroe RR. Maintenance electroconvulsive therapy. Psychiatric Clinics of North America 1991;14:94760. Mukherjee 1994 Mukherjee S, Debsikdar V. Absence of neuroleptic-induced parkinsonism in psychotic patients receiving adjunctive electroconvulsive therapy. Convulsive Therapy 1994;10: 538. NICE 2003 National Institute for Clinical Excellence. Guidance on the use of electroconvulsive therapy. NICE Technology Appraisal Guidance 59. London: National Institute for Clinical Excellence, 2003. NIMH 1976 Guy W. DOTES - Dosage Record and Treatment Emergent Symptom Scale. ECDEU Assessment Manual for Psychopharmacology. Revised. Rockville MD, USA: National Institute of Mental Health, 1976.
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Overall 1962 Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychological Reports 1962;10:799812. Prien 1986 Prien RF, Kupfer D. Continuation drug therapy for major depressive episodes: How long should it be maintained?. American Journal of Psychiatry 1986;143:1823. Prudic 1990 Prudic J, Sackeim HA, Devanand DP. Medication resistance and clinical response to electroconvulsive therapy. Psychiatry Research 1990;31:28796. Robin 1982 Robin A, De Tissera S. Double-blind controlled comparison of the therapeutic effects of low and high energy electroconvulsive therapy. British Journal of Psychiatry 1982; 141:35766. Rose 2003 Rose D, Fleischmann P, Wykes T, Leese M, Bindman J. Patients perspectives on electroconvulsive therapy: systematic review. BMJ 2003;326:13635. Royal College 1995 Royal College of Psychiatrists. The ECT Handbook: The Second Report of the Royal College of Psychiatrists Special Committee on ECT.. London: Royal College of Psychiatrists, 1995. Sackeim 1987 Sackeim HA, Decina P, Kanzler M, Kerr B, Malitz S. Effects of electrode placement on the efcacy of titrated, low-dose ECT. American Journal of Psychiatry 1987;144:144955. Sackeim 1990 Sackeim HA, Prudic J, Devanand DP. The impact of medication resistance and continuation pharmacotherapy on relapse following response to electroconvulsive therapy in major depression. Journal of Clinical Psychopharmocology 1990;10:96104. Sackeim 1991 Sackeim HA, Devanand DP, Prudic J. Stimulus intesity, seizure threshold, and seizure duration: impact on the efcacy and safety of electroconvulsive therapy. Psychiatric Clinics of North America 1991;14:80344. Sackeim 1993 Sackeim HA, Prudic J, Devanand DP, Kierskey JE, Fitzsimons L, Moody BJ, McElhiney MC, Coleman EA, Settembrino JM. Effects of stimulus intensity and electrode placement on the efcay and cognitive effects of electroconvulsive therapy. New England Journal of Medicine 1993;328:83946. Sackeim 2000 Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, Fitzsimons L, Moody BJ, Clark J. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Archives of General Psychiatry 2000;57:42534.
Sackeim 2001 Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JH, Pettinati HM, Geenberg RM, Crowe RR, Cooper TB, Prudic J. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy. Journal of the American Medical Association 2001;285:1299307. Salzman 1980 Salzman C. The use of ECT in the treatment of schizophrenia. American Journal of Psychiatry 1980;137: 103241. Schooler 1993 Schooler NR, Keith SJ. The clinical research base for the treatment of schizophrenia. Psychopharmacology Bulletin 1993;29:43146. Scott 1991 Scott AIF, Weeks DJ, McDonald CF. Continuation electroconvulsive therapy: preliminary guidelines and an illustrative case report. British Journal of Psychiatry 1991; 159:86770. Scott 1992 Scott AIF, Rodger CR, Stocks RH, Shering AP. Is old fashioned electroconvulsive therapy more efcacious? A randomised comparative study of bilateral brief-pulse and bilateral sine-wave treatments. British Journal of Psychiatry 1992;160:3604. Scott 1995 Scott A. ECT and depressive disorders. In: Freeman CP editor(s). The ECT Handbook. The Second Report of the Royal College of Psychiatrists Special Committee on ECT. London: Royal College of Psychiatrists, 1995:35. Shapira 1991 Shapira B, Calev A, Lerer B. Optimal use of electroconvulsive therapy: choosing a treatment schedule. Psychiatric Clinics of North America 1991;14:93546. Shapira 1998 Shapira B, Tubi N, Drexler H, Lidsky D, Calev A, Lerer B. Cost and benet in the choice of ECT schedule. Twice versus three times weekly ECT. British Journal of Psychiatry 1998;172:448. Small 1985 Small JG. Efcacy of electroconvulsive therapy in schizophrenia, mania and other disorders. I. Schizophrenia. Convulsive Therapy 1985;1:26370. Thornley 1998 Thornley B, Adam C. Content and quality of 2000 controlled trials in schizophrenia over 50 years. BMJ 1998; 317:11814. UK ECT Group 2003 The UK ECT Review Group. Efcacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003;361: 799808. Ukoumunne 1999 Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ. Methods for evaluating area-wide and
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organisation-based interventions in health and health care: a systematic review. Health Technology Assessment 1999;3(5): iii92. [MEDLINE: 10982317] Weiner 1986 Weiner RD, Rogers HJ, Davidson JR, Squire LR. Effects of stimulus parameters on cognitive side effects. Annals of the New York Academy of Sciences 1986;462:31525. Weiner 1994 Weiner RD. Treatment optimization with ECT. Psychopharmacology Bulletin 1994;30:31320. Indicates the major publication for the study
33
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Abraham 1987 Methods Allocation: randomly allocated - method not described. Blinding: double. Follow up: 6 months (26 weeks). Diagnosis: schizophrenia (RDC after PSE interview). Setting: Chandigarh, India, in and outpatients. N=22. Age: no group differences. Sex: no group differences. Excluded: prior ECT, onset of illness > 40 years, duration ill > 2 years. History: past medication not reported. 1. Modied ECT (unclear if bi/unilateral): xed number (8 treatments, 2 times / week). N=11. 2. Sham ECT: xed number (8 treatments, 2 per week). N=11. Both groups: triuoperazine, xed dose (20 mg/day) for rst 16 weeks, exible dose (up to 20 mg/day) thereafter. Benzhexal and nitrazepam as necessary Relapse. Mental state: BPRS (18 item). Global impression: CGI Leaving the study early. Average BPRS scores at intake lower than other studies. Proportions globally improved based on CGI scores were kindly supplied by the rst author
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Abrams 1967 Methods Allocation: toss of a coin. Blinding: not described, possibly not blinded. Follow up: after 20 treatments (7 weeks). Diagnosis: acute schizophrenia (clinical consensus), Setting: US Air Force Hospital, Texas, USA, inpatients. N=10. Age: 18-30 years. Sex: not mentioned. Included: onset of illnes less than 3 months.
34
Authors judgement Unclear
Description B - Unclear
Participants
Abrams 1967
(Continued)
History: medication not reported. Interventions 1. Unilateral non dominant ECT three times a week ( 20 treatments) N=4. 2. Unilateral non-dominant ECT 5 times a week (20 treatments) N=6 ECT given at medium setting on a Reuben Reiter Mol-AC II machine Cognitive tests: Weschler memory scale scores (Form I), confusion, disorientation, memory loss, incontinence
Outcomes
Notes Risk of bias Item Allocation concealment? Agarwal 1985 Methods Allocation: randomly divided - method not described. Blinding: double. Follow up: 1 month (preceded by 1 month on 600-1200 mg/day chlorpromazine) Diagnosis: schizophrenia (RDC). Setting: Lucknow, India, in hospital. N=30. Age: range 17-50 years. Sex: not reported. Excluded: ill > 2 years or < 1 month, prior ECT, if improved >50% on BPRS in preceding month. History: past medication not reported, all participants partially unresponsive to antipsychotics 1. Modied ECT (bilateral): xed number (8 treatments, 3 times / week). N=15. 2. Sham ECT: (bilateral): xed number (8 treatments, 3 times / week). N=15 Both groups: chlorpromazine, variable doses (600-1200 mg/day) Mental state: BPRS. Leaving the study early. Unable to use Mental state: BPRS depression subscale (no SD). Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Authors judgement Unclear Description B - Unclear
35
Bagadia 1981 Methods Allocation: randomly allocated - method not described. Blinding: double. Follow up: 6 months (26 weeks). Diagnosis: schizophrenia (clinical consensus). Setting: Bombay, India, outpatients. N=78. Age: not reported. Sex: not reported. Excluded: affective symptoms, given antipsychotics in last 3 weeks, given ECT/insulin therapy in last 8 weeks, organic brain syndrome, epilepsy, physical illness. History: ill >1 month, past medication not reported, pre-trial drug use/response not reported 1. Modied ECT (bilateral) + placebo drug (6 tablets/day): 110 volts for 0.5 secs, 3 in 1st week, 2 times / week thereafter, 6-10 treatments. N=40. 2. Sham ECT + chlorpromazine: 6-10 ECT treatments, 600mg drug per day. N=38 Global impression: CGI. Cognitive tests: memory. Unable to use Mental state: BPRS (no SD). Cognitive tests: test battery average scores (no means, only change scores) One publication reported some additional participants with depression - excluded from this review
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Bagadia 1988 Methods
Allocation: randomised technique - method not described. Blinding: double. Follow up: 20 days, 48 hours after last ECT. Diagnosis: schizophrenia (DSM III) Setting: Bombay, India, outpatients. N=61. Age: 18-65 years; no group differences. Sex: no group differences. Included: ill > 1 month, positive symptoms, clear consciousness. Excluded: schizoaffective disorder, antipsychotics in last 3 weeks, ECT or insulin coma in last 8 weeks, neurological or severe medical illness. History: majority ill more 1-6 years, past treatment not described
Participants
36
Bagadia 1988
(Continued)
Interventions
1. Unmodied bilateral ECT: xed number ( 6 treatments, 3 at 3 day intervals, 3 at 4 day intervals), no antipsychotics, only chloral hydrate permitted. N=31. 2. Unmodied unilateral (right) ECT: number and schedule and medication as above. N=30 Electrical stimulus: sine wave, 110 volts for ~ 0.5 secs in both groups Mental state: BPRS. Global impression: CGI. Leaving study early. Memory: cognitive prole test, subjective forgetfulness. Unable to use Global impression: CGI (no data reported). Mental state: BPRS (no SD). Cognitive test: Cognitive prole test (not validated).
Outcomes
Notes Risk of bias Item Allocation concealment? Baker 1958 Methods Allocation: random allocation - method not described. Blinding: participants not blind, unclear if raters blinded. Follow up: 1 week after last ECT (10 weeks after start of trial) Diagnosis: schizophrenia (clinical consensus). Setting: Surrey, UK, in hospital. N=48. Age: 18-40 years. Sex: all women. Excluded: prior physical treatments. History: 32/48 ill <2 years, all had poor prognostic features but those receiving ECT worst and antipsychotic group, best, pre-trial drug use/response not reported 1. Partly modied ECT (unclear if bi/unilateral): 3 times / week for treatment 1-12, 2 / week for treatment 13-18, 1 / week thereafter, xed number (20). N=18. 2. Insulin coma: 30 comas, 1 / day, 6 times / week. N=15. 3. Chlorpromazine: dose 300 mg / day, 6 days / week for 8 weeks. N=15 All given 6 grains sodium amytal on treatment days, additional treatments not reported, unclear if whether any medication was used in the follow up period Discharged. Relapse. Global impression: not improved. Leaving the study early.
37
Participants
Interventions
Outcomes
Baker 1958
(Continued)
Unable to use Mental state: Wittenborn rating scale (no SD). Psychological tests: average scores (no SD). Notes Risk of bias Item Allocation concealment? Baker 1960 Methods Allocation: random selection procedure - method not described. Blinding: participants not blind, unclear if rater blinded. Follow up: one week after last treatment ( 5 weeks to 10 weeks after start of trial) Diagnosis: schizophrenia (clinical consensus). Setting: Surrey, UK, in hospital. N = 43. Age: 18-43 years. Sex: all female. Included: physically t . History: No details provided; considerd to have a bad prognosis by usual criteria. often had previous treatment with tranquillizers. 1. ECT (Ectonus technique; partly modied with sodium amytal, unclear if bi/unilateral) xed number of 12 treatments, 5 /week for 1 week, 3/week for 2 weeks and 1/week for 1 week. N=10. 2. ECT as above, xed number = 12, 3/week for 3 weeks and 1/week for 1 week. N=14. 3. ECT as above, xed number = 20, 5/week for 1 week, 3/week for 3 weeks, 2/week for 2 weeks and 1/ week for 2 weeks. N=12. 4. ECT as above, xed number = 20, 3/week for 4 weeks, 2/week for 3 weeks, and 2/week for 2 weeks. N=7 No details of additional treatments. Discharged (improved by clinical global impression). Unable to use Mental state: Wittenborn rating scale (no SD). Numbers discharged after fast vs slow treatments (confounded by total number of treatments) Data for the 2 groups given 12 ECT combined and compared with combined data for 2 groups given 20 ECT. Since discharge was based on clinical impression of clincal and social improvement, numbers not discharged were equated with those not improved on global impression Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes
Risk of bias
38
Baker 1960
(Continued)
Item Allocation concealment? Brandon 1985 Methods
Allocation: randomly allocated - used predetermined random numbers. Blinding: double. Follow up: 26 weeks after last ECT (total 30 weeks). Diagnosis: schizophrenia (PSE and Catego class S+). Setting: Leicester, UK, in hospital. N=19. Age: average 36 years. Excluded: consent refused or not obtainable. History: 5 ill <6 months in each group, prior admissions - intervention=0, control=5, prior ECT- intervention=0, control=4 and; prior drug response not reported 1. Modied ECT (unclear if bi/unilateral): 2 times / week, 8 treatments planned. N=9. 2. Sham ECT: 2 times / week, 8 treatments planned. N=10. Additional treatments: previous dose of antipsychotics unchanged during 4 week trial period, mean chlorpromazine equivalents - ECT 317 mg/day, control 273 mg/day, medication and ECT prescribed as clinically indicated in the follow up period Global impression: not improved. Relapse. Leaving the study early. Mental state: Montgomery-Asberg Schizophrenia Scale, Hamilton Depression Rating Scale, visual analog depression and global scales (data skewed, see additional tables) Dose of concurrent chlorpromazine used lower than other trials
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Brill 1959 Methods
Allocation: randomly assigned - method not described. Blinding: double. Follow up: the end of ECT treatment (7 weeks after start of trial) Diagnosis: schizophrenia (clinical consensus). Setting: California, USA. N=97.
39
Participants
Brill 1959
(Continued)
Age: average 35 years, range 18-68. Excluded: organic brain disorders, ECT not indicated or given in last 9 months. History: ECT indicated, ill <1 month to 10 years, mainly chronic, prior ECT in 50%, prior drug response not reported Interventions 1. Unmodied ECT: 3 times / week, xed 20 treatments. N=19. 2. ECT and muscle relaxant: 3 times / week, xed 20 treatments. N=20. 3. ECT and anaesthetic: 3 times / week, xed 20 treatments. N=20. 4. Sham ECT and anaesthetic: 3 times / week, xed 20 treatments. N=20. 5. Sham ECT with nitrous oxide anaesthesiaand anaesthetic: 3 times / week, xed 20 treatments. N=18 Additional treatment: regular hospital activities, no medication reported Global impression: not improved (not improved on 2/3 measures on psychiatric status 9 point scale, Lorr 5 point psychiatric rating scale, psychological status. Leaving the study early. Unable to use Mental state: Lorr Psychiatric Rating Scale scores (data inadequate). Psychological , biochemical and physiological tests: (imprecise statistical results presented) This study also had a comparision group of depressed and schizoaffective participants (N=30). It was impossible to seperate depressed people from those with schizoaffective disorder, so these data are excluded
Outcomes
Notes
Risk of bias Item Allocation concealment? Chanpattana 1999a Methods Allocation: randomised and allocated to treatments by statistician. Blinding: single blind, blind raters. Follow up: 6 months. Diagnosis: schizophrenia (clinical consensus). Setting: two hospitals in Bangkok, and one in Nonthamburi, Thailand, unclear if inpatients or outpatients. N=51. Age: 20-49 years. Sex: 21 M, 24 F. Included: ill >2 years, treatment resistant, BPRS >35 before ECT and < 25 before start of continuation ECT, written consent sequentially to both acute and continuation ECT treatment. Excluded: serious medical conditions, hypersensitivity to anaesthetics, muscle relaxants. History: mean duration ill ~ 12 years SD ~ 6, mean prior admissions ~ 8 SD ~ 6, 33% past ECT responder 1. Continuation ECT : weekly bilateral ECTfor 1 month ( 4 treatments), bimonthly for 5 months ( 10 treatments). N=16. 2. Continuation ECT (as above) + Flupenthixol (Flx) dose (mean 22 mg; SD 3.7 mg). N=17. 3. Flupenthixol, mean dose 22.4mg, SD 2.7 mg. N=18.
40
Participants
Interventions
Chanpattana 1999a
(Continued)
Additional treatments: benzhexol 4- 15 mg/day and diazepam up tp 20 mg/day as needed Outcomes Mental state: BPRS. Relapse: BPRS score >37 on two consecutive ratings 3 days apart. Global functioning: GAF Cognitive assessment: MMSE. Leaving the study early. Phase I: 114 people with reatment resistant schizophrenia treated with bilateral ECT thrice weekly + upenthixol 12-24 mg/day till BPRS <25 or 20 ECT were given. Then each person who demonstrated clinical stability over 3 weeks with 3 ECT / week for 1 week and weekly ECT for 2 weeks during which BPRS remained<25. Responders (58, 51%) were eligible for randomisation in Phase II of the study. Dr. Chanpattana was most helpful in providing additional data
Notes
Risk of bias Item Allocation concealment? Authors judgement Yes Description A - Adequate
Chanpattana 2000 Methods Allocation: randomised and allocated to treatments by statistician. Blinding: double blind. Follow up: 1 week after last ECT ( range 25 - 79 days). Diagnosis: schizophrenia (DSM IV). Setting: Bangkok and Nonthamburi, Thailand, in and outpatients. N=67. Age: 20-49 years. Sex: 30 males, 37 females. Inclusion: acute psychotic exacerbation with BPRS score > 37, age 16-50 years, written consent. Excluded: treatment with depot neuroleptics or ECT in previous 6 months, psychosis secondary to medical or neurological condition or substance abuse, serious medical illness. History: Subtypes- 40 paranoid, 15 disorganised, 3 undifferentiated, 1 catatonic, all subjects were referred for ECT due to failure to respond to adequate doses of neuroleptics. Duration of illness 3-32 years, number of previous admissions 2-26, number of failed adequate neuroleptic trials 2-7, lasting 2.4 -126 months. CPZ equivalent dose 800-2080 mg. 17 subjects had failed earlier trials with upenthixol. BPRS at entry 39-73 1. ECT - dose just above seizure threshold. N=23. 2. ECT - dose two times threshold. N=23. 3. ECT- dose four times threshold. N=21. Bilateral, brief pulse ECT given thrice weekly till BPRS < 25 and maintained over 3 week stabilisaton period (ECT thrice weekly for 1 week and weekly for 2 weeks). Non responders had BPRS scores > 25 after at least 20 ECT Brief pulse ECT given with MECTA SR 1 and Thymatron DGx. Initial threshold etimation done by dose titration
41
Participants
Interventions
Chanpattana 2000
(Continued)
Additional treatments: all subjects were on upenthixol 18-24 mgs/day (CPZ equivalent dose 1200-1600 mg/day). Benzhexol 4-15 mg/day and diazepam up to 10 mg/day used as needed Outcomes Global impression: BPRS < 25 after ECT and maintained over the 3 week stabilisation period ECT treatments: number of treatments and days to rst improvement and till end of study. Leaving the study early. Unable to use Mental state: BPRS (no usable data). Global functioning: GAF (no usable data). Cognitive functions: MMSE (Thai version) (no usable data). Dr. Chanpattana was most helpful in supplying additional data. We have requested Dr. Sackeim to kindly provide us with means and SDs for endpoint BPRS, GAF and MMSE scores
Notes
Doongaji 1973 Methods Allocation: stratied randomisation according to age and duration of illness. Blinding: single blind. Follow up: 3 months. Diagnosis: schizophrenia (clinical consensus). Setting: Bombay, India. outpatients. N=86. Age: 15-45 years. Sex: male and female. Included: right handed, no physical, pharmacological, or psychotherapeutic treatment for 3 months. Excluded: signs and symptoms < 2 months or > 2 years, medical illnesses. History: no details of prior treatments. 1. Unilateral non-dominant ECT 2. Unilateral dominant ECT. 3. Bilateral ECT. All ECT given 3/week for rst 2 weeks and two/week for next two weeks, exible number, minimum 6 treatments, xed voltage of 120 volts Additional treatments: only chloral hydrate. Mental state: BPRS. Leaving the study early. Unable to use Number of ECT treatments (only means, no SD). Cognitive impairment: no usable data, assessment method of doubtful validity
42
Participants
Interventions
Outcomes
Doongaji 1973
(Continued)
Notes
Only 54/86 people completed treatments and only 25 were followed up for 3 months; reasons for drop out not available
Risk of bias Item Allocation concealment? Girish 2003 Methods Allocation: randomised, computer generated randomisation codes, allocation concealed from rater. Blinding: double blind. Follow up: 3 weeks. Diagnosis: non affective, functional catatonia (Schizophrenia 9, PsychNOS 4; ICD-10). Setting: Bangalore, India, inpatients. N =14. Age: average ~ 23 (SD 4). Sex: 11 male, 3 female. Included: people with non-affective, non-organic catatonia, non-responsive (having at least two catatonic signs) to 6-8 mg of lorazepam/ day within 5 days. Excluded: prior recent ECT, depressive catatonia, organicity. History: ill 0.25-120 months, duration of catatonic signs 1-288 weeks, baseline BFCRS scores average ~ 13.3 (SD 3.0) 1. Bilateral modied ECT: thrice weekly till maximum clinical improvement maintained over 1 week (613 treatments; average 8.9) + oral placebo twice daily. N=8. 2. Risperidone: dose 4-6 mg/day in divided doses + Sham ECT twice a week for 3 weeks (xed). N=6 All ECT given after titrating seizure threshold and subsequently marginally suprathreshold doses (> 60 millicouloumbs) delivered; seizures monitored by cuff method and computerised EEG. All participants given Thiopentone (4 mg/kg body weight) and for real ECT succinlycholine (1 mg/kg body weight) and atropine (0.6 mg) Global Impression: not improved at end of 3 weeks and needing further ECT. Leaving the study early. Adverse effects: Columbia Side effects checklist; Simpson Angus rating scale Unable to use Mental state: BFCRS (data skewed, see additional tables), PANNS (no usable data) Details of randomisation, BFCRS (mean and SD) scores kindly provided by the rst author along with the unpublished manuscript Mean duration of illness (SD) in ECT arm 33.0 months(41.9), in Risperidone arm 50.3 months (40.6) ; similarly duration of catatonic signs also longer in Risperidone arm 69.8 weeks(113.79) VS ECT arm 14.9 (20.7) Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes
Risk of bias
43
Girish 2003
(Continued)
Item Allocation concealment?
Authors judgement Yes
Description A - Adequate
Goswami 2001 Methods Allocation: randomised and allocated by anaesthetists using a random number table. Blinding: double blind. Follow up: 6 weeks. Diagnosis: schizophrenia (DSM IV). Setting: New Delhi, India, outpatients. N=31. Age: mean ~ 30 years SD ~ 7. Sex: all male. Included: people with treatment resistant illnesses. Excluded: BPRS score < 45 and CGI severity score < 4. History: mean duration ill ~ 7 years, mean GAF score ~ 25. 1. Bilateral brief pulse ECT three times weekly, mean 14.4 treatments (SD 1.95, range 12-18), stimulus dose 50 - 200% above threshold. N = 17 2. Sham ECT. N= 13. Additional treatments: all subjects were given chlorpromazine in exible doses of 200 -1000 mg/day, trihexphenedyl upto 6 mg/day, intravenous diazepam or promethazine as needed for agitation Mental state: BPRS. Global outcome: CGI. Leaving the study early. Drs. Goswami and Kumar were most helpful in supplying us the manuscript of the unpublished study and additional information, particularly about those leaving the study early (ECT 2; Sham ECT 3; total sample 30; data presented in publication only for 25
Participants
Interventions
Outcomes
Notes
44
Janakiramiah 1981 Methods Allocation: randomly allocated - method not described. Blinding: single (rater blind to treatments). Follow up: after last ECT (6 weeks after start of trial). Diagnosis: schizophrenia (ICD-9). Setting: Bangalore, India, in hospital. N=50. Age: average 29 years, range 15-45. Sex: 32 M, 18 F. Excluded: schizoaffective disorder, organic illness, alcohol, drug abuse. History: ill > 6 months, range 6 months to 2 years, prior drug response not specied 1. Unmodied ECT (bilaterial) + chlorpromazine: 2 times / week, 8-12 treatments, 300 mg/day drug. N=25. 2. Chlorpromazine: dose 300 mg/day. N=25. Additional treatments: paraldehyde as required,use not reported Leaving the study early. Unable to use Global impression: CGI (only means presented). Mental state: Rockland and Pollin Scale (no SD).
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Janakiramiah 1982 Methods Allocation: random allotment - method not described. Blindness: single, rater blind, compromised in a dozen ratings. Follow up: 6 weeks from start of trial (preceded by 300 or 500 mg/day chlorpromazine or equivalent antipsychotic prior to trial Diagnosis: schizophrenia (RDC). Setting: Bangalore, India, in hospital. N=60. Age: 18-42 years. Sex: 37 M, 23 F. Excluded: physical illness, ill > 6 years. History: ill > 2 months if 1st episode, or 1 month if not, duration ill 18 months, duration of current episode ~ 5 months, not on antipsychotic medication or ECT at time of entry to trial, pre-trial drug response unclear Authors judgement Unclear Description B - Unclear
Participants
45
Janakiramiah 1982
(Continued)
Interventions
1. Modied ECT (bilateral) + 300 mg/day chlorpromazine: 3 times / week, 8-15 treatments ensuring modied seizure. N=15. 2. Modied ECT (bilateral) + 500 mg/day chlorpromazine: 3 / week, 8-15 treatments ensuring modied seizure. N=15. 3. Chlorpromazine: dose 300mg/day. N=15. 4. Chlorpromazine: dose 500mg/day. N=15. Additional treatments: not reported. Global impression: CGI. Leaving the study early. Unable to use Mental state: BPRS (no SD).
Outcomes
Notes Risk of bias Item Allocation concealment? May 1968 Methods Allocation: randomised - sequentially numbered opaque envelopes containing a master deck of randomly distributed assignment cards, allocation by research psychologist not involved in treatment, staggered intake. Blinding: single (raters). Follow up: 2-5 years after rst discharge from hospital. Diagnosis: schizophrenia (clinical consensus). Setting: California, USA, in hospital. N=247. Age: average ~ 28 years SD ~ 6, range 16-45. Excluded: previous major somatic therapy or substantial hospital treatment, organic brain disorder, physical illness contraindicating treatments, substance dependance, improvement during evaluation phase or little reasonable prospect of discharge in 2 years. History: rst admission, ill average ~39 months SD ~66, range 1-470, middle prognostic range 1. Modied ECT (uni/bilateral): initially 3 times / week, then 2 and 1 / week, 7-45 treatments, men averaged 19, women 25. N=51. 2. Antipsychotic drugs: triuoperazine (10-120 mg/day, average ~ 35mg/day, additional chlorpromazine given temporarily to 7 participants. N=51. 3. Psychotherapy: individual psychoanlytic (ego-supportive and reality dening) given by residents and supervised by experienced therapists, 7-97 hours. N=49. 4. Psychotherapy plus antipsychotics: drugs in exible doses (4-120 mg) integrated to facilitate psychotherapy. N=49. 5. Milieu therapy: standard care in a conservative, expectant, humanistic environment. N=47 Follow up treatments not controlled. Included antipsychotics, psychotherapy and further ECT (7 people)
46
Participants
Interventions
May 1968
(Continued)
, nursing care, hydrotherapy, occupational, recreational and industrial therapy. Barbiturates prescribed as required Outcomes Death. Global impression: not improved. Discharged. Leaving the study early. Mental state: Menninger Health-Sickness Scale (MHS), Motility Affect Cooperation Communication Scale (MACC), Jenkins Symptom Rating Scale (JSRS). Employment (data skewed, see additional tables). Unable to use Mental state: Psychotic Confusion Scale (data similar to JSRS), Clyde Mood Scale, Shipley Scale, Minnesota Multiphasic Personality inventory (data not usable) Milieu therapy considered placebo for this analysis. Data from reverse cohort analysis of the follow up report not usable for this review. Days rehospitaised taken from reversed cohort analysis as estimated by Wyatt RJ, 1991
Notes
Miller 1953 Methods Allocation: random - method not described Blinding: none. Follow up: 2 weeks after last treatment (6 weeks from start of trial) Diagnosis: catatonic schizophrenia (clinical consensus). Setting: Saskatchewan, Canada, inpatients. N=30. Excluded: physical treatment in previous year. History: hospitalized average 10 years, majority received physical treatment including ECT in past, not in preceding year, homogenous participant prole, all chronic, prior drug response not reported 1. Unmodied ECT (bilateral): 1.5 milliamps, xed 20 treatments over 3 weeks. N=10. 2. Thiopentone anaesthesia + subconvulsive ECT: 5 times / week over 4 weeks. N=10. 3. Sham ECT: 5 / week over 4 weeks. N=10. Additional treatments: not reported. Employment. Unable to use Behavioural assessment: (data difcult to interpret and not clearly relevant) Results of both subconvulsive and sham ECT combined for analysis
Participants
Interventions
Outcomes
Notes
47
Miller 1953
(Continued)
Risk of bias Item Allocation concealment? Naidoo 1956 Methods Allocation: divided at random - no further details. Blinding: double, tablets same colour, raters blinded. Follow up: immediately after last treatment (12 weeks). Diagnosis: schizophrenia (clinical consensus). Setting: Connecticut, USA, in hospital. N=80. Age: average 44 years SD 11, median 43, range 17-74. Exclude: physical illness, low IQ. History: disturbed, chronic, 5 had leucotomy, homogeneous group 1. ECT + placebo: 1 time / week for 6 weeks, fortnightly thereafter. N=20. 2. ECT + reserpine: frequency of ECT as above, week 1 - 5mg IM reserpine / day, week 2-4 - 10mg / day oral, week 3-4 5mg reserpine / day extra if needed, week 5-12 dose maintained or varied as needed. N= 20. 3. Reserpine: dose regimen as above. N=20. 4. Placebo: N=20. Global impression. Leaving the study early. Categorical data for global impression made binary by dichotomising at not any improvement Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Sarita 1998 Methods
Allocation: randomly allocated - method not described. Blinding: double blind. Follow up: 4 weeks. Diagnosis: schizophrenia (ICD -10). Setting: Bangalore, India, in hospital. N=36. Age: 18-45 years.
48
Participants
Sarita 1998
(Continued)
Sex: 21 M, 15 F. Excluded: on neuroleptics < 2 weeks or low doses (haloperidol < 10 mg/day), substance use, physical contraindications to ECT. History: 78% ill >2 years, duration of current episode < 6 months in 27/36 Interventions 1. Modied brief pulse unilateral ECT three times weekly + haloperidol (mean dose 14.2 mg, SD 8.2 mg) . N=12. 2. Modied brief pulse bilateral ECT three times weekly + haloperidol (mean dose 14.6 mg, SD 5.8 mg) . N=12. 3. Sham ECT three times weekly + haloperidol (mean dose 18.3 mg, SD 7.2 mg). N=12 ECT given in xed dose 168 mC for treatments 1-6 and if needed increased to 336 mC subsequently Global impression: CGI Adverse effects: memory tests. Unable to use Mental state: BPRS. Adverse effects: extrapyramidal symptoms -UKU side effects rating scale Logical verbal memory (Data skewed, see additional tables) Dr Gangadhar was most helpful in supplying additional data.
Outcomes
Notes Risk of bias Item Allocation concealment? Sarkar 1994 Methods
Allocation: randomised by investigator who concealed allocation in opaque envelopes and not associated with any other part of study or patient care. Blinding: double. Follow up: 6 months after last treatment. Diagnosis: provisional poor prognosis schizophreniform disorder (DSM IIIR ). Setting: Bangalore, India, in hospital for treatment phase. N=30. Age: mid 20s. Sex: all Male. Excluded: contraindications to ECT, medical problems, associated or past psychiatric diagnosis, history of ECT or psychoactive drugs use. History: ill <2 months. 1. Modied ECT (bilateral): sine wave stimulus, 140 V for 0.6s, seizure duration monitored by Hamilton cuff method, 25s seizure duration ensured at each treatment, 3 times / week, 6 treatments. N=15. 2. Sham ECT: 3 times / week, 6 treatments. N=15. Additional treatments: xed dose haloperidol 15 mg/day, additional antipsychotics permitted but not
49
Participants
Interventions
Sarkar 1994
(Continued)
used Outcomes Global impression: Global Assessment Scale (5 points). Leaving the study early. Unable to use Mental state: BPRS (data skewed). Adjustment: Katz Adjustment scale (data skewed). Dr. Andrade was most helpful in supplying addtional information
Notes Risk of bias Item Allocation concealment?
Authors judgement Yes
Description A - Adequate
Small 1982 Methods Allocation: randomised within predesignated ratio (10:6:10:3 see order of interventions) no further details. Blinding: double, for drugs, single for ECT, interviews taped, edited and rated. Follow up: course 4 weeks, 6 weeks after end of course, 1 year follow up Diagnosis: schizophrenia (Feigners criteria, SADS-L). Setting: Indianapolis, USA, in hospital. N=75. Age: average ~ 25 years SD ~ 10. Sex: 41 M, 34 F. Excluded: ill < 6 months, in hospital > 1 year in last 2 years, contraindications to interventions, low IQ, recent substance abuse. History: 23 ill <6 months, 20 ill 6-24 months, 32 > 2 years. 1. ECT + thiothixene: non-dominant unilateral, Medcraft model MkII sine wave, 3 times / week, individualised number, miniminum 12, thiothixene - see below. N=25. 2. ECT + placebo: dose - see above. N=16. 3. Thiothixene: dose individual titrated, limited by dose, maximim 16mg / day. N=26. 4. Placebo: N=8. Global impression (derived from those terminated due to non-response or clinical deterioration) Leaving the study early. Unable to use Global impression: CGI (no usable data). Mental state: BPRS, Emotional Blunting Scale, SRSS (no usable data). Behaviour: NOSIE (no usable data). Adverse effects: AIMS, DOTES (no usable data). Dr Small has been most helpful in supplying additional unpublished data; however no usable data extractable for many primary outcomes
Participants
Interventions
Outcomes
Notes
50
Small 1982
(Continued)
Risk of bias Item Allocation concealment? Taylor 1980 Methods Allocation: random assignment, stratied according to sex and depression scores, - method not described. Blinding: participants blind to treatment assignment, research assesments blind but supplemented by non-blind clinical assessments. Follow up: 3 months after last treatment, (4 months after start of trial) Diagnosis: paranoid schizophrenia (19), catatonic schizophrenia (PSE). Setting: London, UK, mostly in hospital, some day patients. N=20. Age: range 18-50 years. Excluded: illness <6 months, hospitalized > 2 years in last 5, unable to function outside hospital <6 months in last year, organic brain dysfunction, developmental disorder, physical illness, substance dependance, ECT in last 2 years, recovered with antipsychotics 2 weeks prior to study. History: partially non-responsive to antipsychotics, middle prognostic group 1. Modied ECT (bilateral and unilateral): brief pulses 25J, 3 times / week, 8-12 treatments. N=10. 2. Sham ECT, 3 times / week, 8-12 treatments. N=10. Additional treatments: chlorpromazine 300 mg per day or equivalent, after ECT, additional antipsychotics permitted, occupational therapy Global impression: not improved. Relapse. Leaving the study early. Unable to use Mental state: Global Psychopathlogy, Comprehensive Psychiatric Rating Scale, Beck Depressive Inventory (inadequate data reported) Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Authors judgement Unclear Description B - Unclear
51
Ukpong 2002 Methods Allocation: randomly allocated by ballot, methods not described. Blinding: both participants and rater blind to allotment. Follow up: 5 months (17 weeks after last treatment). Diagnosis: schizophrenia (ICD 10 criteria). Setting: Ilesa, Osun state, Nigeria, majority in hospital. N=20. Age: for completers- ECT mean (SD) 27.7 years (10.3), SECT mean (SD) 24.3 years (5.5). Sex: 10 M, 10 F. Excluded: prior ECT, ill more than two years, onset after 45 years, organic cerebral cause, signcant physical illness. History: ill < 6 months 12, > six months 8, mean (SD) duration in months for completers ECT 8.4 (9. 2) SECT 5.0 (6.0), rst episode 11, second episode 8, third episode 1. Subtype: paranoid 11, catatonic 4, hebephrenic 1, undifferentiated 4 1. Modied ECT + chlorpromazine: bilateral, Ectron Duopulse machine, constant current, 40 pulses per second for 3 seconds, twice weekly, six treatments (xed), chlorpromazine: 300 mgs, adjustable, mean daily dose 306.5 mg (no SD). N=11. 2. Sham ECT + chlorpromazine: twice weekly for six treatments (xed), chlorpromazine as above, mean daily dose 285 mg (no SD). N=9 Anaesthesia with thiopentone (200-300 mg), suxamethonuim (50-100 mg), atropine (0.6-1.2 mg IV). All patients stablilised on chlorpromazine 300 mg (adjustable) for 2 weeks before real or sham ECT Adverse effects. Leaving the study early. Unable to use Mental state: BPRS (total and positive subscale scores), SANS scores, (data skewed, see additional tables) . CGI (no data provided). CGI data and details of items omitted in modied BPRS scale used, randomisation and allocation sought from authors
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Ungvari 1982 Methods Allocation: random selection - no further details. Blinding: double. Follow up: at end of course of ECT - 6 days. Diagnosis: systematic schizophrenia (33), unsystematic schizophrenia (42) (clinical consensus). Setting: Budapest, Hungary, in hospital. N=75.
52
Participants
Ungvari 1982
(Continued)
Age: average 32 years, range 20-50 years. Sex: 37 M, 38 F. Excluded: somatic illness. History: acute exacerbations, ill 1 months - 18 years, prior treatment unclear, 94% had been previously treated at the clinic Interventions 1. ECT + standard dose haloperidol; ECT 2/day on 3 occasions over 6 days, haloperidol 4.5 - 9 mg/day, ave. 6.5 mg/day. N=36. 2. High dose haloperidol: 40 -120 mg IM on day 1, adjusted according to tolerence thereafter for 6 days, range 50 -120 mg/day, average 72 mg/day. N=39 Adverse events. Leaving the study early. Unable to use Mental state: FCRS (data not usable).
Outcomes
Notes Risk of bias Item Allocation concealment? Wu 1989 Methods Allocation: chosen at random, method not described. Blinding: single blind. Follow up: 3 months. Diagnosis: schizophrenia (28), unspecied psychosis (12)(CMCCDC). N=40. Setting: Tai Am, China, in hospital. Age: 18-43 years Sex: all male. Included: BPRS at least 3 questions scored 4 or above, loss of insight scored 6/7 or 7/7. Excluded: contraindications to ECT. History: Duration ill 6 months - 5 years, no data on prior treatment 1. Bilateral unmodied ECT (105 -125 mA) thrice a week (mean 7.5, SD 0.9, range 6-10 treatments) + chlorpromazine 300-650 mg/day (mean 472.5 mg, SD 51.8 mg). N=20. 2. Chlorpromazine 300-600mg/day (mean 558.5 mg, SD 78.4 mg). N=20 Additional treatments: not mentioned. Mental state: BPRS (modied to add a question on insight, graded 0-7). Leaving the study early. Adverse effects: serial numbers and picture recall. Authors judgement Unclear Description B - Unclear
Participants
Interventions
Outcomes
Notes
Electroconvulsive therapy for schizophrenia (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 53
Wu 1989
(Continued)
Risk of bias Item Allocation concealment? Authors judgement Unclear Description B - Unclear
BFCRS - Bush Francis Catatonia Rating Scale BFCRS - Bush Francis Catatonia Rating Scale BPRS - Brief Psychiatric Rating Scale CGI - Clinical Global Impressions CMCCDC -Chinese Medical Council Clinical Diagnostic Criteria CPZ - Chlorpromazine DSM - Diagnostic and Statistical Manual FCRS - Factor Construct Rating Scale FRS - First Rank Symptoms GAF - Global Assessment of Functioning ICD - International Classication of Diseases mA - milli amperes MMSE - Mini Mental State Exam PANNS - Positive and Negative Symptom Scale for schizophrenia PANNS - Positive and Negative Syndrome Scale PSE - Present State Examination RDC - Research Diagnosis Criteria SANS - Schedule for the Assessment of Negative Symptoms SD - standard deviation SRSS - Self-Rated Symptom Scale Sz - schizophrenia vs - versus
Characteristics of excluded studies [ordered by study ID]
Study Aoba 1983 Arato 1980 Ayers 1960 Baker 1961 Barker 1960
Reason for exclusion Allocation: not randomised, case series with plasma studies before and after ECT Allocation: not randomised, case series with crossover of anaesthetic technique Allocation: not randomised, retrospective case series. Allocation: not randomised, case series. Allocation: randomised. Participants: people with schizophrenia and depression. Interventions: ECT modied or unmodied, each person received both methods on a random basis, not a
54
(Continued)
focus of this review for this version Benatov 1996 Berg 1959 Bhatia 1987 Bhatia 1998 Bowes 1956 Brewer 1972 Chanpattana 1997 Chanpattana 1998 Chanpattana 1999b Chanpattana 1999c Chanpattana 1999d Allocation: not random, case report. Allocation: not randomised, before and after design. Allocation: not randomised, case series. Allocation: not randomised, case report. Allocation: not randomised, case series. Allocation: not randomsed, open trial. Allocation: not randomised, case series. Allocation: not randomised, case series. Allocation: not randomised, case series. Allocation: not randomised, open-trial. Allocation: not randomised, retrospective chart review of matched ECT responders drawn from two hospitals who were part of an earlier randomised trial Allocation: not random, double blind, controlled clinical trial Allocation: not randomised, open trial. Allocation: not randomised, case series. Allocation: not randomised; case series with patients given different stimulus intensities, though randomised to two different makes of ECT machines Allocation: unclear, assigned equal numbers to each group. Allocation: not randomised, assigned sequentially. Allocation: not randomised, assigned sequentially. Allocation: not randomised, open trial. Allocation: randomised, intra-individual, crossover. Participants: people with depression (n=10), and schizophrenia (n = 2). Outcomes: no data presented separately for people with schizophrenia Allocation: not randomised, case series.
Chanpattana 1999e Chanpattana 2000b Chanpattana 2000c Chanpattana 2002
Chatterjee 1980 Childers 1961 Childers 1964 Cronholm 1961 dElia 1970
Das 1991
55
(Continued)
Delva 1996
Allocation: unclear, double blind study. Participants: people with mental disorders. Interventions: bitemporal versus right unilateral versus bifrontal of threshold level electroconvulsive therapy, no sham ECT Allocation: not randomised, case series. Allocation: unclear, double blind study. Participants: people with severe depression. Allocation: not randomised, alternate allocation. Allocation: randomly selected electroshock referrals, not randomly allocated to treatment groups Allocation: not randomised, case report. Allocation: not randomised, open trial. Allocation: randomised. Participants: people with schizophrenia. Interventions: ECT versus sham ECT versus thiopentone versus prochlorperazine. Outcomes: no data presented in usable form. Reviewers attempted to contact author - no reply Allocation: unclear. Participants: people with mixed diagnoses, not schizophrenia alone Allocation: randomised. Participants: people with schizophrenia. Interventions: electroacupuncture plus reduced dose of antipsychotics versus antipsychotics alone; no ECT or sham ECT comparison arm Allocation: unclear, crossover study. Participants: people with mixed diagnoses, not schizophrenia alone Allocation: randomised, crossover design. Participants: mixed diagnoses. Interventions: propofol versus methohexital as induction anaesthetic agents, ECT was not randomised Allocation: randomised. Participants: people with schizophrenia. Interventions: reserpine versus placebo, the two groups also given ECT, but not randomised to ECT Allocation: not randomised, case series. Allocation: not randomised, case report. Allocation: randomised. Participants: people with mixed diagnoses, not schizophrenia alone
56
Dodwell 1989 Early 1999
El Islam 1970 Fink 1958 Frankenberg 1993 Friedel 1986 Gambill 1966
Gander 1967
Gang 1997
Gangadhar 2000
Geretsegger 1998
Goller 1960
Gottlieb 1951 Green 1994 Greenblatt 1962
(Continued)
Gujavarty 1987 Guo 2000 Hargreaves 1972 He 2001
Allocation: not randomised, retrospective chart review. Allocation: not randomised, retrospective chart review. Allocation: not randomised, case series. Allocation: randomised. Participants: people with schizophrenia. Interventions: right unilateral ECT versus left unilateral ECT; not a focus of this review Allocation: not randomised, assigned alphabetically. Allocation: not randomised, open trial. Allocation: not randomised, a random sample of people given two treatments, allocation not stated Allocation: not randomised, open label study, controlled clinical trial Allocation: not randomised, case report. Allocation: not randomised, case control study. Allocation: not randomised, assigned alternately. Allocation: not randomised, review of trials. Allocation: randomised. Participants: people with major depressive disorder. Allocation: not randomised, participants drew playing cards and were assigned according to value of drawn card Allocation: randomised, method unclear, possibly sequentially (since other studies by same author used sequential randomisation). Not blinded. Participants: 37 males with schizophrenia; 18 with chronic schizophrenia hospitalized continuously on average for 15 years, 19 with more recent illness. Interventions: ECT thrice weekly (ECT) versus ECT twice daily 6 days a week (RECT). Both groups received 20 treatments. Outcomes: Ward quality; discharge rates. Numbers of people assigned to each treatment not reported Allocation: not randomised, assigned alternately. Allocation: not randomised, case report. Allocation: not randomised, case series.
Heath 1964 Hirose 2001 Hrebicek 1965 Ikeji 1999 James 1999 Jiang 1989 Johnson 1960 Johnstone 1997 Kellner 1999
King 1958
King 1959
King 1960 Klapheke 1999 Konig 1990
57
(Continued)
Krystal 1993
Allocation: unclear, intraindividual cross over trial. Participants: people with mixed diagnoses. Interventions: bilateral versus unilateral ECT, high and low dose treatments. Outcomes: ictal EEG changes, no clinical outcomes. Allocation: not randomised, case series. Allocation: not randomised, case series. Allocation: randomised. Participants: people with schizophrenia and people with mania. Interventions: ECT versus chlorpromazine. Outcomes: not presented separately by diagnosis, unable to use Allocation: not randomised. Allocation: not randomised, controlled clinical trial. Allocation: unclear, double blind study. Participants: people with schizophrenia. Interventions: naloxone versus saline, all received ECT. Allocation: unclear, double blind placebo controlled trial. Participants: people with depression, obsessive compulsive disorder, schizophrenia. Interventions: inositol versus placebo, not ECT. Allocation: unclear, double blind crossover. Participants: people with mixed diagnoses. Interventions: inositol versus placebo. Allocation: not randomised, retrospective case series. Allocation: unclear, controlled clinical trial. Allocation: not randomised, consecutive case series. Allocation: not randomised, controlled clinical trial. Allocation: unclear, double blind study. Participants: people with major depression and catatonic schizophrenia. Interventions: two different doses of atacurium as anaesthetic agent for ECT, not ECT itself Allocation: unclear, controlled clinical trial. Participants: people with depression. Intervention: ketamine versus methohexital as anaesthetic agents for ECT Allocation: not randomised, controlled clinical trial.
Kupchik 2000 Landy 1991 Langsley 1959
Laurell 1970a Laurell 1970b Levin 1990
Levine 1995
Levine 1997
Lewis 1982 Li 2002 Ligthart 1956 Lingl 1964 Lui 1993
McInnes 1972
Meyendorf 1981
58
(Continued)
Mezquita 1973 Milstein 1990 Murillo 1973 Natani 1983
Allocation: not randomised, controlled clinical trial. Allocation: not randomised, case series. Allocation: not randomised, retrospective case series with prospective follow up Allocation: randomly assigned. Participants: people with schizophrenia (90). Interventions: ECT versus ECT + haloperidol versus haloperidol. Outcomes: Rockland Symptom Rating Scale, Psychiatric disability Rating Scale, only means presented, no usable data Allocation: Unknown conference abstract; no further details available Allocation: paired intraindividual comparisons, order of treatments randomised, not people Allocated: randomised. Participants: people with schizophrenia (1), schizoaffective (4), bipolar disorder (3) and people with depression (24). Interventions: different schedules of stimulus doses for ECT. Outcomes: elicitation of seizures, electrical dose requirements, no clinical data Allocation: not randomised, controlled clinical trial. Allocation: not randomised, assigned alternately. Allocation: not randomised, retrospective case series. Allocation: not randomised, divided into three groups, controlled clinical trial Allocation: randomised. Participants: people with schizophrenia, people with affective psychosis, others. Interventions: bilateral versus unilateral ECT. Outcomes: not reported separately for people with schizophrenia, no usable data Allocation: not randomised, case series. Allocation: not random, case report. Allocation: not randomised, case series. Allocation: randomised. Participants: people with schizophrenia. Interventions: urothyl induced convulsion versus ECT, no sham ECT Allocation: not randomised, assigned every 5th white patient Allocation: unclear; controlled clinical trial.
59
Ostzovscki 1997 Ottosson 1960 Petrides 1996
Peyman 1956 Pisvejc 1998 Rahman 1968 Ray 1962 Reichert 1976
Rhode 1961 Safferman 1992 Sajatovic 1993 Small 1968
Smith 1967 Stenback 1957
(Continued)
Sullivan 1974 Swoboda 2001 Tang 2003 Ulett 1956 Vojtechovsky 1970
Allocation: not randomised, retrospective chart review. Allocation: not randomised, case series. Allocation: not randomised, controlled clinical trial Allocation: not randomised, matched groups assigned respectively to four treatment groups Allocation: unclear. Participants: people with schizophrenia. Interventions: centrophenoxin versus placebo, all given ECT. Allocation: not randomised, review. Allocation: not randomised, alternately assigned. Allocation: randomised. Participants: mixed psychiatric inpatients. Interventions: discussion group versus activity group, some patients received ECT but were not randomised for ECT Allocation: not randomised, case series. Allocation: randomised. Participants: people with schizophrenia. Interventions: electric acupuncture convulsive therapy versus ECT; no sham ECT; used different electrode types (round plates, acupuncture needles, clips) and placements that overlapped between intervention arms
Weinstein 1971 Wessels 1972 West 1982
Xie 1994 Xue 1985
Characteristics of ongoing studies [ordered by study ID]

Petrides 2000 Trial name or title Methods Participants Diagnosis: schizophrenia. Expected N=64. Age: 18- 60. Sex: both. History: receiving >2 X 400 mg doses of chlorpromazine equivalents for > 4 weeks (may include newer antipsychotics), having substantial psychotic symptoms despite > 12 weeks of treatment with clozapine (at least 8 weeks at a consistent dose) 1. ECT plus clozapine. 2. Clozapine. Unknown.
Interventions
60
Petrides 2000
(Continued)
Outcomes Starting date
Unknown. Study start: December 2000. Study completion: November 2003. Christopher Phillips, RN Tel: 718-470-8163 E-mail: cphillip@lij.edu Zucker Hillside Hospital Glen Oaks New York, 11004, USA Georgios Petrides, MD Tel: 718-470-8569 E-mail: gpetrides@lij.edu Christine J Svetina, Ph.D Tel: 718-470-8448 E-mail: csvetina@lij.edu Allocation: randomized, open label. Funded: NIMH. Health Authority: United States: Federal Government Web: http://www.clinicaltrials.gov/ct/show/NCT00042224
Contact information
Notes
61
DATA AND ANALYSES
Comparison 1. ECT versus PLACEBO or SHAM ECT
Outcome or subgroup title 1 Global impression: 1a. Not improved 1.1 at end of course of ECT 1.2 short term (after course of ECT) 1.3 medium term 2 Global impression: 2. Not discharged from hospital 3 Global impression: 3. Relapse 3.1 short term 3.2 medium term 3.3 long term 4 Global impression: 4. Average endpoint score (MHS scale, high score=good) 4.1 short term 4.2 long term (2 years) 5 Mental state: 1. Average endpoint score (BPRS, high score = poor) 5.1 mid-course ECT 5.2 mid-course ECT (treatment resistant illness) 5.3 at end of course of ECT 5.4 at end of course of ECT (treatment resistant illness) 5.5 short term after course of ECT 5.6 medium term after course of ECT 6 Mental state: 2. Average endpoint score - medium term (Jenkin scale, high score = poor) 7 Behaviour: Average endpoint score - medium term (MACC scale, high score = good) 8 Employment: 1. On ward 9 Leaving the study early 9.1 short-medium term 9.2 long term (5 years) 10 Adverse effects: 1. Memory
No. of studies 10 10 1 1 1 4 2 1 1 1
No. of participants
Statistical method Risk Ratio (M-H, Fixed, 95% CI)
Effect size Subtotals only 0.72 [0.59, 0.86] 0.71 [0.29, 1.75] 0.43 [0.14, 1.35] 0.59 [0.34, 1.01] 0.81 [0.37, 1.75] 0.26 [0.03, 2.20] 7.0 [0.41, 120.16] 0.69 [0.26, 1.84] Subtotals only
392 30 30 98 165 47 20 98
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
1 1 4
90 86
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
-1.80 [-6.57, 2.97] 1.30 [-3.31, 5.91] Subtotals only
2 1 2 1 2 1 1
52 25 52 25 52 16 90
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
-4.72 [-8.87, -0.57] 6.0 [0.10, 11.90] -6.14 [-10.01, -2.27] 3.60 [-3.69, 10.89] -6.38 [-10.74, -2.02] -0.29 [-3.49, 2.91] -2.10 [-5.19, 0.99]
90
Mean Difference (IV, Fixed, 95% CI)
4.10 [-0.40, 8.60]
1 12 12 1 1
30 405 98
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
0.95 [0.75, 1.19] Subtotals only 0.85 [0.58, 1.25] 0.97 [0.77, 1.24] Subtotals only
62
10.1 verbal memory (Paired associate learning, high scores = good) 10.2 visual memory (high scores = good) 11 Adverse effects: 2. Other 11.1 Headache 12 Death - within three years after treatment
24
-3.10 [-6.59, 0.39]
1 1 1 1
24 16 16 98
Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
-12.00 [-23.11, -4. 89] 7.20 [0.45, 114.89] 7.20 [0.45, 114.89] Not estimable
Comparison 2. ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT
No. of studies 7 No. of participants
Outcome or subgroup title 1 Global impression: 1. Not improved - at end of course of ECT 1.1 ECT alone vs antipsychotic drugs alone 1.2 ECT and placebo vs antipsychotics and sham ECT 1.3 ECT and antipsychotic drugs vs antipsychotic drugs alone 2 Global impression: 2. Relapse short term (vs antipsychotics alone) 3 Global impression: 3. Not discharged from hospital (vs antipsychotics alone) 4 Global impression: 4. Average endpoint score (MHS, high = good) 4.1 short term - vs antipsychotics 4.2 long term (2 years) - vs antipsychotics 5 Mental state: 1. Average endpoint score (BPRS, high score = poor) 5.1 vs antipsychotic drugs mid course ECT 5.2 vs antisychotic drugs - at end of course of ECT 5.3 vs antipsychotic drugs short term after course of ECT
Effect size Subtotals only
3 2 3
175 52 151
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
2.18 [1.31, 3.63] 1.10 [0.74, 1.63] 1.15 [0.73, 1.82]
33
Risk Ratio (M-H, Fixed, 95% CI)
0.33 [0.13, 0.85]
135
1.98 [0.97, 4.03]
Subtotals only
1 1 1
95 90
-5.30 [-9.31, -1.29] -1.20 [-5.60, 3.20] Subtotals only
1 1 1
40 40 40
-2.40 [-5.77, 0.97] -3.90 [-5.52, -2.28] -2.0 [-9.57, 5.57]

63
5.4 vs antispychotic drugs medium term after course of ECT 6 Mental state: 2. Average endpoint score (Jenkin scale, high = poor) 6.1 vs antipsychotics medium term 7 Behaviour: Average endpoint score - medium term (MACC, high = good) 7.1 vs antipsychotics 8 Leaving the study early 8.1 short-medium term - vs antipsychotics 8.2 long term (5 years) - vs antipsychotics 8.3 short term - vs antipsychotics and sham ECT 9 Adverse effects: 1. Memory - vs antispychotics and sham ECT 9.1 subjective impairment at end of course of ECT 9.2 objective impairment at end of course of ECT 10 Adverse effects: 2. Memory - vs antipsychotics 10.1 serial numbers and picture recall at end of course of ECT (high scores = good) 10.2 serial numbers and picture recall 9 weeks after ECT (high scores = good) 11 Adverse effects: 3. Extrapyramidal side effects - vs antipsychotics and sham ECT 12 Adverse effects: 4. Extrapyramidal side effects - vs antipsychotics 12.1 acute dystonia 12.2 akathisia 13 Adverse effects: 5. Other - vs antipsychotics and sham ECT 13.1 drowsiness 13.2 pain 13.3 giddiness 13.4 weakness 13.5 allergic reaction 14 Adverse events: 6. Other - vs antipsychotics 14.1 orthostatic hypotension
40
-7.20 [-14.08, -0.32]
Subtotals only
1 1
94
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
2.20 [-0.35, 4.75] Subtotals only
1 10 9 1 1 2 2 1 1 1
95 645 529 102 14
Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
-6.0 [-9.18, -2.82] 0.98 [0.83, 1.17] 0.99 [0.78, 1.27] 0.97 [0.77, 1.23] Not estimable Subtotals only 2.68 [0.79, 9.06] Not estimable Subtotals only -4.90 [-9.02, -0.78]
34 20
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
40
40
-0.30 [-4.77, 4.17]
52
0.09 [0.01, 0.69]
Subtotals only
1 2 2 1 2 1 1 1 1 1
75 89
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
0.54 [0.11, 2.78] 0.46 [0.11, 1.89] Subtotals only 0.10 [0.01, 1.75] 2.18 [0.80, 5.94] 0.6 [0.11, 3.19] 0.9 [0.06, 13.36] 2.71 [0.12, 62.70] Subtotals only 0.36 [0.04, 3.32]
64
38 52 38 38 38
75
15 Death within three years of treatment - vs antipsychotics
Subtotals only
Comparison 3. ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS
Outcome or subgroup title 1 Global impression: 1. Not improved - at end of course of ECT 1.1 vs psychotherapy alone 1.2 vs psychotherapy and antipsychotic drugs 2 Global impression: 2. Not discharged from hospital 2.1 vs psychotherapy alone 2.2 vs psychotherapy and antipsychotic drugs 3 Global impression: 3. Average endpoint score (MHS, high score = good) 3.1 short term - vs psychotherapy alone 3.2 short term - vs psychotherapy and antipsychotic drugs 3.3 long term (2 years) - vs psychotherapy alone 3.4 long term (2 years) - vs psychotherapy and antipsychotic drugs 4 Mental state: Average endpoint score - medium term (Jenkin scale, high = poor) 4.1 vs psychotherapy alone 4.2 vs psychotherapy and antipsychotic drugs 5 Behaviour: Average endpoint score - medium term (MACC scale; high = good) 5.1 vs psychotherapy alone 5.2 vs psychotherapy and antipsychotic drugs 6 Leaving the study early 6.1 short-medium term - vs psychotherapy alone
No. of studies 1
No. of participants
1 1 1 1 1 1
102 100
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
0.74 [0.42, 1.30] 1.92 [0.85, 4.36] Subtotals only 0.71 [0.40, 1.25] 1.92 [0.85, 4.36] Subtotals only
100 100
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
1 1
93 90
3.0 [-0.89, 6.89] -5.0 [-9.46, -0.54]
1 1
90 91
4.5 [0.24, 8.76] -0.5 [-5.04, 4.04]
Subtotals only
1 1 1
93 91
-3.70 [-6.66, -0.74] 2.60 [0.27, 4.93] Subtotals only
1 1 1 1
93 91
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
4.40 [0.14, 8.66] -6.10 [-9.23, -2.97] Subtotals only 1.28 [0.30, 5.43]
65
100
6.2 short-medium term - vs psychotherapy and antipsychotic drugs 6.3 long term (5 years) - vs psychotherapy alone 6.4 long term (5 years) - vs psychotherapy and antipsychotic drugs 7 Death - within three years after treatment
100
0.77 [0.22, 2.70]
1 1
100 100
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
0.96 [0.76, 1.21] 0.91 [0.73, 1.14]
149
0.63 [0.03, 15.31]
Comparison 4. ECT versus INSULIN COMA THERAPY
Outcome or subgroup title 1 Global impression: Not improved - at end of course of ECT 2 Leaving the study early 3 Relapse
No. of studies 1
No. of participants 33
Effect size 0.69 [0.26, 1.83]
1 1
33 33
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)
0.28 [0.03, 2.40] 0.67 [0.22, 2.05]
Comparison 5. CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS
Outcome or subgroup title 1 Global impression: 1. Average endpoint score (GAF, high scores = good) 1.1 CECT vs antipsychotic drugs 1.2 CECT vs CECT + antipsychotics 1.3 CECT + antipsychotics vs antipsychotics 2 Global impression: 2. Relapse 2.1 CECT vs antipsychotic drugs 2.2 CECT + antipsychotics vs CECT 2.3 CECT + antipsychotics vs antipsychotics 3 Mental state: Average endpoint score ( BPRS, high scores = poor)
No. of studies 1
No. of participants
Statistical method Mean Difference (IV, Fixed, 95% CI)
1 1 1 1 1 1 1 1
30 30 30
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
-1.24 [-6.36, 3.88] -20.3 [-29.12, -11. 48] 19.06 [9.65, 28.47] Subtotals only 1.0 [0.83, 1.21] 0.43 [0.23, 0.81] 0.43 [0.23, 0.81] Subtotals only
30 30 30
66
3.1 CECT vs antipsychotic drugs 3.2 CECT vs CECT + antipsychotic drugs 3.3 CECT + antipsychotics vs antipsychotic drugs 4 Leaving study early 4.1 CECT vs antipsychotics 4.2 CECT + antipsychotics vs CECT 4.3 CECT + antipsychotics vs antipsychotics 5 Adverse effects - cognitive: Average endpoint score (MMSE, high scores = good) 5.1 CECT vs antipsychotic drugs 5.2 CECT vs CECT + antipsychotic drugs 5.3 CECT + antipsychotics vs antipsychotic drugs
1 1 1 1 1 1 1 1
30 30 30
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
-1.63 [-9.07, 5.81] 18.12 [8.61, 27.63] -19.75 [-29.22, -10. 28] Subtotals only 0.33 [0.04, 2.85] 2.0 [0.20, 19.78] 0.67 [0.13, 3.44] Subtotals only
30 30 30
1 1 1
30 30 30
0.04 [-3.33, 3.41] -2.32 [-5.28, 0.64] 2.36 [-0.62, 5.34]
Comparison 6. ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT
Outcome or subgroup title 1 Global impression: 1. Not improved 1.1 mid-course ECT 1.2 end of course of ECT 1.3 medium term (12 weeks) 2 Mental state: 1. Average endpoint score (BPRS, high = poor) 2.1 mid-course ECT 2.2 end of course of ECT 3 Adverse effects: 1. Memory - at end of course of ECT 3.1 visual memory - impaired 3.2 unaided recall - impaired 3.3 confabulation -present 3.4 subjective forgetfulness 4 Adverse effects: 2. Memory average end point score 4.1 verbal memory ( paired associate learning, high scores = good)
No. of studies 2 2 2 1 1
No. of participants
Effect size Subtotals only 1.02 [0.55, 1.88] 0.79 [0.45, 1.39] 0.69 [0.40, 1.21] Subtotals only
78 78 54
Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
1 1 1 1 1 1 1 1 1
36 36
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Not estimable -0.5 [-6.56, 5.56] Subtotals only 1.33 [0.57, 3.14] 0.6 [0.17, 2.18] 0.6 [0.17, 2.18] 4.0 [0.49, 32.72] Subtotals only 0.70 [-2.76, 4.16]
40 40 40 40
24
67
4.2 visual memory (high scores = good)
24
3.90 [-4.94, 12.74]
Comparison 7. ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT
Outcome or subgroup title 1 Global impression: not improved 1.1 threshold ECT vs 2 times threshold ECT 1.2 threshold ECT vs 4 times threshold ECT 1.3 2 times threshold ECT vs 4 times threshold ECT 2 Leaving study early 2.1 threshold ECT vs 2 times threshold ECT 2.2 threshold ECT vs 4 times threshold ECT 2.3 2 times threshold ECT vs 4 times threshold ECT 3 SUBGROUP of people in remission - Number of ECT treatments: 1. To rst improvement 3.1 threshold ECT vs 2 times threshold ECT 3.2 threshold ECT vs 4 times threshold ECT 3.3 2 times threshold ECT vs 4 times threshold ECT 4 SUBGROUP of people in remission - Number ECT treatments: 2. At end of course of ECT 4.1 theshold ECT vs 2 times threshold ECT 4.2 threshold ECT vs 4 times threshold ECT 4.3 2 times threshold ECT vs 4 times threshold ECT 5 SUBGROUP of people in remission - Days of treatment: 1. To rst improvement 5.1 threshold ECT vs 2 times threshold ECT 5.2 threshold ECT vs 4 times threshold ECT
No. of studies 1 1 1 1 1 1 1 1 1
No. of participants
Statistical method Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size Subtotals only 1.0 [0.58, 1.74] 1.00 [0.57, 1.75] 1.00 [0.57, 1.75] Subtotals only 1.0 [0.15, 6.51] 1.83 [0.18, 18.70] 1.83 [0.18, 18.70] Subtotals only
46 44 44
46 44 44
1 1 1 1
22 22 22
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
6.1 [2.39, 9.81] 9.40 [6.32, 12.48] 3.23 [0.82, 5.64] Subtotals only
1 1 1 1
22 22 22
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
6.10 [2.39, 9.81] 9.40 [6.32, 12.48] 3.30 [0.89, 5.71] Subtotals only
1 1
22 22
19.0 [7.07, 30.93] 28.4 [18.54, 38.26]

68
5.3 2 times threshold ECT vs 4 times threshold ECT 6 SUBGROUP of people in remission - Days of treatment: 2. At end of course of ECT 6.1 threshold ECT vs 2 times threshold ECT 6.2 threshold ECT vs 4 times threshold ECT 6.3 2 times threshold ECT vs 4 times threshold ECT
1 1
22
9.40 [2.05, 16.75] Subtotals only
1 1 1
22 22 22
18.90 [6.94, 30.86] 18.90 [6.94, 30.86] 9.5 [2.10, 16.90]
Comparison 8. ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL)
Outcome or subgroup title 1 Adverse effects: 1. Cognitve impairment clinically apparent 2 Adverse effects: 2. Memory - Average endpoint score (Weshler memory scale-form I, high score = good)
No. of studies 1 1
No. of participants 10 10
Statistical method Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size Not estimable 2.97 [-8.45, 14.39]
Comparison 9. ECT - NUMBER OF TREATMENTS: 12 versus 20 TREATMENTS
Outcome or subgroup title 1 Global impression: Not improved
No. of studies 1
No. of participants 43
Effect size 2.53 [1.13, 5.66]
69
Analysis 1.1. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 1 Global impression: 1a. Not improved.
Review: Electroconvulsive therapy for schizophrenia
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 1 Global impression: 1a. Not improved
Study or subgroup
Treatment n/N
Control n/N
Risk Ratio M-H,Fixed,95% CI
Weight
1 at end of course of ECT Abraham 1987 Brandon 1985 Brill 1959 Goswami 2001 May 1968 Naidoo 1956 Sarita 1998 Sarkar 1994 Small 1982 Taylor 1980 3/14 4/9 15/38 14/17 14/51 15/20 12/24 10/15 8/16 1/10 9/14 10/10 13/29 10/13 22/47 18/20 5/12 10/15 6/8 9/10 7.5 % 8.4 % 12.3 % 9.5 % 19.1 % 15.0 % 5.6 % 8.4 % 6.7 % 7.5 % 0.33 [ 0.11, 0.98 ] 0.47 [ 0.23, 0.95 ] 0.88 [ 0.50, 1.55 ] 1.07 [ 0.74, 1.55 ] 0.59 [ 0.34, 1.01 ] 0.83 [ 0.62, 1.12 ] 1.20 [ 0.55, 2.62 ] 1.00 [ 0.60, 1.66 ] 0.67 [ 0.35, 1.25 ] 0.11 [ 0.02, 0.72 ]
Subtotal (95% CI)
214
178
100.0 %
0.72 [ 0.59, 0.86 ]
Total events: 96 (Treatment), 112 (Control) Heterogeneity: Chi2 = 17.18, df = 9 (P = 0.05); I2 =48% Test for overall effect: Z = 3.53 (P = 0.00041) 2 short term (after course of ECT) Sarkar 1994 5/15 7/15 100.0 % 0.71 [ 0.29, 1.75 ]
Subtotal (95% CI)

Total events: 5 (Treatment), 7 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.74 (P = 0.46) 3 medium term Sarkar 1994
15
15
100.0 %
0.71 [ 0.29, 1.75 ]
3/15
7/15
100.0 %
0.43 [ 0.14, 1.35 ]
Subtotal (95% CI)

Total events: 3 (Treatment), 7 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.45 (P = 0.15)
15
15
100.0 %
0.43 [ 0.14, 1.35 ]
0.1 0.2
0.5
10
70
Analysis 1.2. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 2 Global impression: 2. Not discharged from hospital.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 2 Global impression: 2. Not discharged from hospital
Study or subgroup
Treatment n/N
Control n/N 22/47
Weight
May 1968
14/51
100.0 %
0.59 [ 0.34, 1.01 ]
Total (95% CI)

Heterogeneity: not applicable
51
47
100.0 %
0.59 [ 0.34, 1.01 ]
Total events: 14 (Treatment), 22 (Control) Test for overall effect: Z = 1.94 (P = 0.053)
0.1 0.2
0.5
10
Favours treatment
Favours control
71
Analysis 1.3. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 3 Global impression: 3. Relapse.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 3 Global impression: 3. Relapse
Study or subgroup
Treatment n/N
Control n/N
Weight
1 short term Abraham 1987 Brandon 1985 0/14 0/9 1/14 2/10 11.8 % 18.7 % 0.33 [ 0.01, 7.55 ] 0.22 [ 0.01, 4.05 ]
Subtotal (95% CI)

Total events: 0 (Treatment), 3 (Control)
23
24
30.5 %
0.26 [ 0.03, 2.20 ]
Heterogeneity: Chi2 = 0.04, df = 1 (P = 0.85); I2 =0.0% Test for overall effect: Z = 1.23 (P = 0.22) 2 medium term Taylor 1980 3/10 0/10 3.9 % 7.00 [ 0.41, 120.16 ]
Subtotal (95% CI)

Total events: 3 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.34 (P = 0.18) 3 long term May 1968
10
10
3.9 %
7.00 [ 0.41, 120.16 ]
6/51
8/47
65.5 %
0.69 [ 0.26, 1.84 ]
Subtotal (95% CI)

51
47
65.5 %
0.69 [ 0.26, 1.84 ]
Total (95% CI)

84
81
100.0 %
0.81 [ 0.37, 1.75 ]
Heterogeneity: Chi2 = 3.39, df = 3 (P = 0.34); I2 =11% Test for overall effect: Z = 0.54 (P = 0.59)
0.001 0.01 0.1 Favours treatment
10 100 1000 Favours control
72
Analysis 1.4. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 4 Global impression: 4. Average endpoint score (MHS scale, high score=good).
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 4 Global impression: 4. Average endpoint score (MHS scale, high score=good)
Study or subgroup
Treatment N Mean(SD)
Control N Mean(SD)
Mean Difference IV,Fixed,95% CI
Weight
1 short term May 1968 47 24.7 (10.4) 43 26.5 (12.5) 100.0 % -1.80 [ -6.57, 2.97 ]
Subtotal (95% CI)

47
43
100.0 %
-1.80 [ -6.57, 2.97 ]
Test for overall effect: Z = 0.74 (P = 0.46) 2 long term (2 years) May 1968 44 45.3 (10.7) 42 44 (11.1) 100.0 % 1.30 [ -3.31, 5.91 ]
Subtotal (95% CI)

44
42
100.0 %
1.30 [ -3.31, 5.91 ]
Test for overall effect: Z = 0.55 (P = 0.58) Test for subgroup differences: Chi2 = 0.84, df = 1 (P = 0.36), I2 =0.0%
-10
-5
10
73
Analysis 1.5. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 5 Mental state: 1. Average endpoint score (BPRS, high score = poor).
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 5 Mental state: 1. Average endpoint score (BPRS, high score = poor)
Study or subgroup
Control N Mean(SD)
Weight
1 mid-course ECT Abraham 1987 Agarwal 1985 11 15 13.4 (6.9) 44.13 (7.08) 11 15 19.5 (7.3) 47.53 (9.04) 48.9 % 51.1 % -6.10 [ -12.04, -0.16 ] -3.40 [ -9.21, 2.41 ]
Subtotal (95% CI)
26
26
100.0 %
-4.72 [ -8.87, -0.57 ]
Heterogeneity: Chi2 = 0.41, df = 1 (P = 0.52); I2 =0.0% Test for overall effect: Z = 2.23 (P = 0.026) 2 mid-course ECT (treatment resistant illness) Goswami 2001 15 48.6 (7.9) 10 42.6 (7) 100.0 % 6.00 [ 0.10, 11.90 ]
Subtotal (95% CI)

15
10
100.0 %
6.00 [ 0.10, 11.90 ]
Test for overall effect: Z = 1.99 (P = 0.046) 3 at end of course of ECT Abraham 1987 Agarwal 1985 11 15 10.5 (4.3) 36.4 (7) 11 15 17 (7.7) 42.1 (9) 55.1 % 44.9 % -6.50 [ -11.71, -1.29 ] -5.70 [ -11.47, 0.07 ]
Subtotal (95% CI)
26
26
100.0 %
-6.14 [ -10.01, -2.27 ]
Heterogeneity: Chi2 = 0.04, df = 1 (P = 0.84); I2 =0.0% Test for overall effect: Z = 3.11 (P = 0.0019) 4 at end of course of ECT (treatment resistant illness) Goswami 2001 15 44 (7.6) 10 40.4 (10) 100.0 % 3.60 [ -3.69, 10.89 ]
Subtotal (95% CI)

15
10
100.0 %
3.60 [ -3.69, 10.89 ]
Test for overall effect: Z = 0.97 (P = 0.33) 5 short term after course of ECT Abraham 1987 Agarwal 1985 11 15 8.3 (4) 30.2 (8.9) 11 15 15 (9.2) 36.2 (9.1) 54.1 % 45.9 % -6.70 [ -12.63, -0.77 ] -6.00 [ -12.44, 0.44 ]
Subtotal (95% CI)
26
26
100.0 %
-6.38 [ -10.74, -2.02 ]
Heterogeneity: Chi2 = 0.02, df = 1 (P = 0.88); I2 =0.0% Test for overall effect: Z = 2.87 (P = 0.0042) 6 medium term after course of ECT Ukpong 2002 9 1 (3) 7 1.29 (3.42) 100.0 % -0.29 [ -3.49, 2.91 ]
Subtotal (95% CI)

100.0 %
-0.29 [ -3.49, 2.91 ]
Test for overall effect: Z = 0.18 (P = 0.86) Test for subgroup differences: Chi2 = 20.03, df = 5 (P = 0.00), I2 =75%
-10
-5
10
74
Analysis 1.6. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 6 Mental state: 2. Average endpoint score - medium term (Jenkin scale, high score = poor).
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 6 Mental state: 2. Average endpoint score - medium term (Jenkin scale, high score = poor)
Study or subgroup
Treatment N Mean(SD) 25.6 (6.7)
Control N 43 Mean(SD) 27.7 (8.1)
Weight
May 1968
47
100.0 %
-2.10 [ -5.19, 0.99 ]
Total (95% CI)

47
43
100.0 %
-2.10 [ -5.19, 0.99 ]
Test for overall effect: Z = 1.33 (P = 0.18) Test for subgroup differences: Not applicable
-10
-5
10
Analysis 1.7. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 7 Behaviour: Average endpoint score - medium term (MACC scale, high score = good).
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 7 Behaviour: Average endpoint score - medium term (MACC scale, high score = good)
Study or subgroup
Weight
May 1968
47
100.0 %
4.10 [ -0.40, 8.60 ]
Total (95% CI)

47
43
100.0 %
4.10 [ -0.40, 8.60 ]
-10
-5
10
75
Analysis 1.8. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 8 Employment: 1. On ward.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 8 Employment: 1. On ward
Study or subgroup
Treatment n/N
Control n/N 19/20
Weight
Miller 1953
9/10
100.0 %
0.95 [ 0.75, 1.19 ]
Total (95% CI)

10
20
100.0 %
0.95 [ 0.75, 1.19 ]
0.1 0.2
0.5
10
76
Analysis 1.9. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 9 Leaving the study early.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 9 Leaving the study early
Study or subgroup
Treatment n/N
Control n/N
1 short-medium term Abraham 1987 Agarwal 1985 Brandon 1985 Goswami 2001 May 1968 Miller 1953 Naidoo 1956 Sarita 1998 Sarkar 1994 Small 1982 Taylor 1980 Ukpong 2002 3/14 0/15 0/9 2/17 4/51 0/10 2/20 0/24 2/15 15/16 0/10 2/11 3/14 0/15 2/10 3/13 4/47 0/20 0/20 0/12 4/15 8/8 0/10 2/9 1.00 [ 0.24, 4.13 ] 0.0 [ 0.0, 0.0 ] 0.22 [ 0.01, 4.05 ] 0.51 [ 0.10, 2.62 ] 0.92 [ 0.24, 3.48 ] 0.0 [ 0.0, 0.0 ] 5.00 [ 0.26, 98.00 ] 0.0 [ 0.0, 0.0 ] 0.50 [ 0.11, 2.33 ] 0.97 [ 0.78, 1.20 ] 0.0 [ 0.0, 0.0 ] 0.82 [ 0.14, 4.71 ]
Subtotal (95% CI)

212
193
0.85 [ 0.58, 1.25 ]
Heterogeneity: Chi2 = 4.43, df = 7 (P = 0.73); I2 =0.0% Test for overall effect: Z = 0.83 (P = 0.41) 2 long term (5 years) May 1968 37/51 35/47 0.97 [ 0.77, 1.24 ]
Subtotal (95% CI)

51
47
0.97 [ 0.77, 1.24 ]
0.1 0.2
0.5
10
77
Analysis 1.10. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 10 Adverse effects: 1. Memory.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 10 Adverse effects: 1. Memory
Study or subgroup
Control N Mean(SD)
Weight
1 verbal memory (Paired associate learning, high scores = good) Sarita 1998 12 9.7 (4.7) 12 12.8 (4) 100.0 % -3.10 [ -6.59, 0.39 ]
Subtotal (95% CI)

12
12
100.0 %
-3.10 [ -6.59, 0.39 ]
Test for overall effect: Z = 1.74 (P = 0.082) 2 visual memory (high scores = good) Sarita 1998 12 28.5 (12.7) 12 42.5 (9.9) 100.0 % -14.00 [ -23.11, -4.89 ]
Subtotal (95% CI)

12
12
100.0 %
-14.00 [ -23.11, -4.89 ]
-100
-50
50
100
Favours control
Favours treatment
78
Analysis 1.11. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 11 Adverse effects: 2. Other.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 11 Adverse effects: 2. Other
Study or subgroup
Treatment n/N
Control n/N
Weight
1 Headache Ukpong 2002 4/9 0/7 100.0 % 7.20 [ 0.45, 114.89 ]
Total (95% CI)

Total events: 4 (Treatment), 0 (Control) Heterogeneity: not applicable
100.0 %
7.20 [ 0.45, 114.89 ]
Test for overall effect: Z = 1.40 (P = 0.16)
0.1 0.2
0.5
10
Favours treatment
Favours control
Analysis 1.12. Comparison 1 ECT versus PLACEBO or SHAM ECT, Outcome 12 Death - within three years after treatment.
Comparison: 1 ECT versus PLACEBO or SHAM ECT Outcome: 12 Death - within three years after treatment
Study or subgroup
Treatment n/N
Control n/N 0/47
Risk Ratio M-H,Fixed,95% CI 0.0 [ 0.0, 0.0 ]
May 1968
0/51
Total (95% CI)

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P < 0.00001)
51
47
0.0 [ 0.0, 0.0 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
79
Analysis 2.1. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 1 Global impression: 1. Not improved - at end of course of ECT.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 1 Global impression: 1. Not improved - at end of course of ECT
Study or subgroup
Treatment n/N
Control n/N
Weight
1 ECT alone vs antipsychotic drugs alone Baker 1958 May 1968 Naidoo 1956 5/18 14/51 15/20 4/15 5/51 6/20 28.4 % 32.5 % 39.1 % 1.04 [ 0.34, 3.20 ] 2.80 [ 1.09, 7.20 ] 2.50 [ 1.22, 5.11 ]
Subtotal (95% CI)

89
86
100.0 %
2.18 [ 1.31, 3.63 ]
Heterogeneity: Chi2 = 2.07, df = 2 (P = 0.35); I2 =4% Test for overall effect: Z = 3.01 (P = 0.0026) 2 ECT and placebo vs antipsychotics and sham ECT Bagadia 1981 Girish 2003 15/20 4/8 12/18 3/6 78.7 % 21.3 % 1.13 [ 0.74, 1.70 ] 1.00 [ 0.35, 2.88 ]
Subtotal (95% CI)

28
24
100.0 %
1.10 [ 0.74, 1.63 ]
Heterogeneity: Chi2 = 0.04, df = 1 (P = 0.84); I2 =0.0% Test for overall effect: Z = 0.47 (P = 0.64) 3 ECT and antipsychotic drugs vs antipsychotic drugs alone Janakiramiah 1982 Naidoo 1956 Small 1982 8/30 3/20 15/25 8/30 6/20 9/26 35.1 % 26.3 % 38.7 % 1.00 [ 0.43, 2.31 ] 0.50 [ 0.14, 1.73 ] 1.73 [ 0.93, 3.21 ]
Subtotal (95% CI)

75
76
100.0 %
1.15 [ 0.73, 1.82 ]
Heterogeneity: Chi2 = 3.53, df = 2 (P = 0.17); I2 =43% Test for overall effect: Z = 0.61 (P = 0.54)
0.1 0.2
0.5
10
favours treatment
favours control
80
Analysis 2.2. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 2 Global impression: 2. Relapse - short term (vs antipsychotics alone).
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 2 Global impression: 2. Relapse - short term (vs antipsychotics alone)
Study or subgroup
Treatment n/N
Control n/N 10/15
Weight
Baker 1958
4/18
100.0 %
0.33 [ 0.13, 0.85 ]
Total (95% CI)

18
15
100.0 %
0.33 [ 0.13, 0.85 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
Analysis 2.3. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 3 Global impression: 3. Not discharged from hospital (vs antipsychotics alone).
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 3 Global impression: 3. Not discharged from hospital (vs antipsychotics alone)
Study or subgroup
Treatment n/N
Control n/N 4/15 5/51
Weight
Baker 1958 May 1968
5/18 14/51
46.6 % 53.4 %
1.04 [ 0.34, 3.20 ] 2.80 [ 1.09, 7.20 ]
Total (95% CI)
69
66
100.0 %
1.98 [ 0.97, 4.03 ]
Total events: 19 (Treatment), 9 (Control) Heterogeneity: Chi2 = 1.78, df = 1 (P = 0.18); I2 =44% Test for overall effect: Z = 1.89 (P = 0.059)
0.1 0.2
0.5
10
favours treatment
favours control
81
Analysis 2.4. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 4 Global impression: 4. Average endpoint score (MHS, high = good).
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 4 Global impression: 4. Average endpoint score (MHS, high = good)
Study or subgroup
Control N Mean(SD)
Weight
1 short term - vs antipsychotics May 1968 47 24.7 (10.4) 48 30 (9.5) 100.0 % -5.30 [ -9.31, -1.29 ]
Subtotal (95% CI)

47
48
100.0 %
-5.30 [ -9.31, -1.29 ]
Test for overall effect: Z = 2.59 (P = 0.0095) 2 long term (2 years) - vs antipsychotics May 1968 44 45.3 (10.7) 46 46.5 (10.6) 100.0 % -1.20 [ -5.60, 3.20 ]
Subtotal (95% CI)

44
46
100.0 %
-1.20 [ -5.60, 3.20 ]
-10
-5
10
favours control
favours treatment
82
Analysis 2.5. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 5 Mental state: 1. Average endpoint score (BPRS, high score = poor).
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 5 Mental state: 1. Average endpoint score (BPRS, high score = poor)
Study or subgroup
Control N Mean(SD)
Weight
1 vs antipsychotic drugs - mid course ECT Wu 1989 20 52.1 (7) 20 54.5 (3.2) 100.0 % -2.40 [ -5.77, 0.97 ]
Subtotal (95% CI)

20
20
100.0 %
-2.40 [ -5.77, 0.97 ]
Test for overall effect: Z = 1.39 (P = 0.16) 2 vs antisychotic drugs - at end of course of ECT Wu 1989 20 44.5 (3.5) 20 48.4 (1.2) 100.0 % -3.90 [ -5.52, -2.28 ]
Subtotal (95% CI)

20
20
100.0 %
-3.90 [ -5.52, -2.28 ]
Test for overall effect: Z = 4.71 (P < 0.00001) 3 vs antipsychotic drugs - short term after course of ECT Wu 1989 20 41.9 (12.9) 20 43.9 (11.5) 100.0 % -2.00 [ -9.57, 5.57 ]
Subtotal (95% CI)

20
20
100.0 %
-2.00 [ -9.57, 5.57 ]
Test for overall effect: Z = 0.52 (P = 0.60) 4 vs antispychotic drugs - medium term after course of ECT Wu 1989 20 26.6 (8) 20 33.8 (13.5) 100.0 % -7.20 [ -14.08, -0.32 ]
Subtotal (95% CI)

20
20
100.0 %
-7.20 [ -14.08, -0.32 ]
-10
-5
10
Favours treatment
Favours control
83
Analysis 2.6. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 6 Mental state: 2. Average endpoint score (Jenkin scale, high = poor).
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 6 Mental state: 2. Average endpoint score (Jenkin scale, high = poor)
Study or subgroup
Control N Mean(SD)
Weight
1 vs antipsychotics - medium term May 1968 47 25.6 (6.7) 47 23.4 (5.9) 100.0 % 2.20 [ -0.35, 4.75 ]
Subtotal (95% CI)

47
47
100.0 %
2.20 [ -0.35, 4.75 ]
-10
-5
10
favours treatment
favours control
84
Analysis 2.7. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 7 Behaviour: Average endpoint score - medium term (MACC, high = good).
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 7 Behaviour: Average endpoint score - medium term (MACC, high = good)
Study or subgroup
Control N Mean(SD)
Weight
1 vs antipsychotics May 1968 47 41.9 (8.8) 48 47.9 (6.9) 100.0 % -6.00 [ -9.18, -2.82 ]
Subtotal (95% CI)

47
48
100.0 %
-6.00 [ -9.18, -2.82 ]
-10
-5
10
favours control
favours treatment
85
Analysis 2.8. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 8 Leaving the study early.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 8 Leaving the study early
Study or subgroup
Treatment n/N
Control n/N
1 short-medium term - vs antipsychotics Bagadia 1981 Baker 1958 Janakiramiah 1981 Janakiramiah 1982 May 1968 Naidoo 1956 Small 1982 Ungvari 1982 Wu 1989 20/40 1/18 0/25 0/30 4/51 2/20 21/25 0/36 0/20 20/38 1/15 0/25 0/30 3/51 1/20 23/26 0/39 0/20 0.95 [ 0.62, 1.46 ] 0.83 [ 0.06, 12.22 ] 0.0 [ 0.0, 0.0 ] 0.0 [ 0.0, 0.0 ] 1.33 [ 0.31, 5.66 ] 2.00 [ 0.20, 20.33 ] 0.95 [ 0.76, 1.18 ] 0.0 [ 0.0, 0.0 ] 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

265
264
0.99 [ 0.78, 1.27 ]
Heterogeneity: Chi2 = 0.72, df = 4 (P = 0.95); I2 =0.0% Test for overall effect: Z = 0.06 (P = 0.95) 2 long term (5 years) - vs antipsychotics May 1968 37/51 38/51 0.97 [ 0.77, 1.23 ]
Subtotal (95% CI)

Total events: 37 (Treatment), 38 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.22 (P = 0.82) 3 short term - vs antipsychotics and sham ECT Girish 2003
51
51
0.97 [ 0.77, 1.23 ]
0/8
0/6
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 [ 0.0, 0.0 ]
Total (95% CI)

324
321
0.98 [ 0.83, 1.17 ]
Heterogeneity: Chi2 = 0.68, df = 5 (P = 0.98); I2 =0.0% Test for overall effect: Z = 0.18 (P = 0.86)
0.1 0.2
0.5
10
favours treatment
favours control
86
Analysis 2.9. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 9 Adverse effects: 1. Memory - vs antispychotics and sham ECT.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 9 Adverse effects: 1. Memory - vs antispychotics and sham ECT
Study or subgroup
Treatment n/N
Control n/N
1 subjective impairment at end of course of ECT Bagadia 1981 Girish 2003 5/12 4/8 2/8 0/6 1.67 [ 0.42, 6.59 ] 7.00 [ 0.45, 109.47 ]
Subtotal (95% CI)

20
14
2.68 [ 0.79, 9.06 ]
Heterogeneity: Chi2 = 0.93, df = 1 (P = 0.34); I2 =0.0% Test for overall effect: Z = 1.59 (P = 0.11) 2 objective impairment at end of course of ECT Bagadia 1981 0/12 0/8 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

12
0.0 [ 0.0, 0.0 ]
0.1 0.2
0.5
10
favours treatment
favours control
87
Analysis 2.10. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 10 Adverse effects: 2. Memory - vs antipsychotics.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 10 Adverse effects: 2. Memory - vs antipsychotics
Study or subgroup
Control N Mean(SD)
Weight
1 serial numbers and picture recall at end of course of ECT (high scores = good) Wu 1989 20 25.2 (6.9) 20 30.1 (6.4) 100.0 % -4.90 [ -9.02, -0.78 ]
Subtotal (95% CI)

20
20
100.0 %
-4.90 [ -9.02, -0.78 ]
Test for overall effect: Z = 2.33 (P = 0.020) 2 serial numbers and picture recall 9 weeks after ECT (high scores = good) Wu 1989 20 34.5 (7.5) 20 34.8 (6.9) 100.0 % -0.30 [ -4.77, 4.17 ]
Subtotal (95% CI)

20
20
100.0 %
-0.30 [ -4.77, 4.17 ]
-10
-5
10
Favours control
Favours treatment
88
Analysis 2.11. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 11 Adverse effects: 3. Extrapyramidal side effects - vs antipsychotics and sham ECT.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 11 Adverse effects: 3. Extrapyramidal side effects - vs antipsychotics and sham ECT
Study or subgroup
Treatment n/N
Control n/N 5/18 3/6
Weight
Bagadia 1981 Girish 2003
0/20 0/8
59.5 % 40.5 %
0.08 [ 0.00, 1.39 ] 0.11 [ 0.01, 1.82 ]
Total (95% CI)
28
24
100.0 %
0.09 [ 0.01, 0.69 ]
Total events: 0 (Treatment), 8 (Control) Heterogeneity: Chi2 = 0.02, df = 1 (P = 0.88); I2 =0.0% Test for overall effect: Z = 2.32 (P = 0.020)
0.1 0.2
0.5
10
Favours treatment
Favours control
89
Analysis 2.12. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 12 Adverse effects: 4. Extrapyramidal side effects - vs antipsychotics.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 12 Adverse effects: 4. Extrapyramidal side effects - vs antipsychotics
Study or subgroup
Treatment n/N
Control n/N
Weight
1 acute dystonia Ungvari 1982 2/36 4/39 100.0 % 0.54 [ 0.11, 2.78 ]
Subtotal (95% CI)

Total events: 2 (Treatment), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.73 (P = 0.46) 2 akathisia Girish 2003 Ungvari 1982
36
39
100.0 %
0.54 [ 0.11, 2.78 ]
0/8 2/36
1/6 4/39
30.5 % 69.5 %
0.26 [ 0.01, 5.44 ] 0.54 [ 0.11, 2.78 ]
Subtotal (95% CI)

44
45
100.0 %
0.46 [ 0.11, 1.89 ]
Heterogeneity: Chi2 = 0.17, df = 1 (P = 0.68); I2 =0.0% Test for overall effect: Z = 1.08 (P = 0.28)
0.1 0.2
0.5
10
Favours treatment
Favours control
90
Analysis 2.13. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 13 Adverse effects: 5. Other - vs antipsychotics and sham ECT.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 13 Adverse effects: 5. Other - vs antipsychotics and sham ECT
Study or subgroup
Treatment n/N
Control n/N
Weight
1 drowsiness Bagadia 1981 0/20 4/18 100.0 % 0.10 [ 0.01, 1.75 ]
Subtotal (95% CI)

Total events: 0 (Treatment), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.58 (P = 0.11) 2 pain Bagadia 1981 Girish 2003
20
18
100.0 %
0.10 [ 0.01, 1.75 ]
5/20 6/8
4/18 0/6
88.2 % 11.8 %
1.13 [ 0.36, 3.55 ] 10.11 [ 0.68, 150.68 ]
Subtotal (95% CI)

28
24
100.0 %
2.18 [ 0.80, 5.94 ]
Heterogeneity: Chi2 = 2.51, df = 1 (P = 0.11); I2 =60% Test for overall effect: Z = 1.53 (P = 0.13) 3 giddiness Bagadia 1981 2/20 3/18 100.0 % 0.60 [ 0.11, 3.19 ]
Subtotal (95% CI)

Total events: 2 (Treatment), 3 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.60 (P = 0.55) 4 weakness Bagadia 1981
20
18
100.0 %
0.60 [ 0.11, 3.19 ]
1/20
1/18
100.0 %
0.90 [ 0.06, 13.36 ]
Subtotal (95% CI)

Total events: 1 (Treatment), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.08 (P = 0.94) 5 allergic reaction Bagadia 1981
20
18
100.0 %
0.90 [ 0.06, 13.36 ]
1/20
0/18
100.0 %
2.71 [ 0.12, 62.70 ]
Subtotal (95% CI)

20
18
100.0 %
2.71 [ 0.12, 62.70 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
91
Analysis 2.14. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 14 Adverse events: 6. Other - vs antipsychotics.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 14 Adverse events: 6. Other - vs antipsychotics
Study or subgroup
Treatment n/N
Control n/N
Weight
1 orthostatic hypotension Ungvari 1982 1/36 3/39 100.0 % 0.36 [ 0.04, 3.32 ]
Subtotal (95% CI)

36
39
100.0 %
0.36 [ 0.04, 3.32 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
Analysis 2.15. Comparison 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT, Outcome 15 Death within three years of treatment - vs antipsychotics.
Comparison: 2 ECT with or without ANTIPSYCHOTIC DRUGS versus ANTIPSYCHOTIC DRUGS with or without SHAM ECT Outcome: 15 Death within three years of treatment - vs antipsychotics
Study or subgroup
Treatment n/N
Control n/N 1/98
May 1968
0/51
Subtotal (95% CI)

0.0 [ 0.0, 0.0 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
92
Analysis 3.1. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 1 Global impression: 1. Not improved - at end of course of ECT.
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 1 Global impression: 1. Not improved - at end of course of ECT
Study or subgroup
Treatment n/N
Control n/N
Weight
1 vs psychotherapy alone May 1968 14/51 19/51 100.0 % 0.74 [ 0.42, 1.30 ]
Subtotal (95% CI)

51
51
100.0 %
0.74 [ 0.42, 1.30 ]
2 vs psychotherapy and antipsychotic drugs May 1968 14/51 7/49 100.0 % 1.92 [ 0.85, 4.36 ]
Subtotal (95% CI)

51
49
100.0 %
1.92 [ 0.85, 4.36 ]
0.1 0.2
0.5
10
favours treatment
favours control
93
Analysis 3.2. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 2 Global impression: 2. Not discharged from hospital.
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 2 Global impression: 2. Not discharged from hospital
Study or subgroup
Treatment n/N
Control n/N
Weight
1 vs psychotherapy alone May 1968 14/51 19/49 100.0 % 0.71 [ 0.40, 1.25 ]
Subtotal (95% CI)

51
49
100.0 %
0.71 [ 0.40, 1.25 ]
2 vs psychotherapy and antipsychotic drugs May 1968 14/51 7/49 100.0 % 1.92 [ 0.85, 4.36 ]
Subtotal (95% CI)

51
49
100.0 %
1.92 [ 0.85, 4.36 ]
0.1 0.2
0.5
10
favours treatment
favours control
94
Analysis 3.3. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 3 Global impression: 3. Average endpoint score (MHS, high score = good).
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 3 Global impression: 3. Average endpoint score (MHS, high score = good)
Study or subgroup
Control N Mean(SD)
Weight
1 short term - vs psychotherapy alone May 1968 47 24.7 (10.4) 46 21.7 (8.7) 100.0 % 3.00 [ -0.89, 6.89 ]
Subtotal (95% CI)

47
46
100.0 %
3.00 [ -0.89, 6.89 ]
Test for overall effect: Z = 1.51 (P = 0.13) 2 short term - vs psychotherapy and antipsychotic drugs May 1968 47 24.7 (10.4) 43 29.7 (11.1) 100.0 % -5.00 [ -9.46, -0.54 ]
Subtotal (95% CI)

47
43
100.0 %
-5.00 [ -9.46, -0.54 ]
Test for overall effect: Z = 2.20 (P = 0.028) 3 long term (2 years) - vs psychotherapy alone May 1968 44 45.3 (10.7) 46 40.8 (9.9) 100.0 % 4.50 [ 0.24, 8.76 ]
Subtotal (95% CI)

44
46
100.0 %
4.50 [ 0.24, 8.76 ]
Test for overall effect: Z = 2.07 (P = 0.039) 4 long term (2 years) - vs psychotherapy and antipsychotic drugs May 1968 44 45.3 (10.7) 47 45.8 (11.4) 100.0 % -0.50 [ -5.04, 4.04 ]
Subtotal (95% CI)

44
47
100.0 %
-0.50 [ -5.04, 4.04 ]
-10
-5
10
favours control
favours treatment
95
Analysis 3.4. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 4 Mental state: Average endpoint score - medium term (Jenkin scale, high = poor).
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 4 Mental state: Average endpoint score - medium term (Jenkin scale, high = poor)
Study or subgroup
Control N Mean(SD)
Weight
1 vs psychotherapy alone May 1968 47 25.6 (6.7) 46 29.3 (7.8) 100.0 % -3.70 [ -6.66, -0.74 ]
Subtotal (95% CI)

47
46
100.0 %
-3.70 [ -6.66, -0.74 ]
Test for overall effect: Z = 2.45 (P = 0.014) 2 vs psychotherapy and antipsychotic drugs May 1968 47 25.6 (6.7) 44 23 (4.5) 100.0 % 2.60 [ 0.27, 4.93 ]
Subtotal (95% CI)

47
44
100.0 %
2.60 [ 0.27, 4.93 ]
-10
-5
10
favours treatment
favours control
96
Analysis 3.5. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 5 Behaviour: Average endpoint score - medium term (MACC scale; high = good).
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 5 Behaviour: Average endpoint score - medium term (MACC scale; high = good)
Study or subgroup
Control N Mean(SD)
Weight
1 vs psychotherapy alone May 1968 47 41.9 (8.8) 46 37.5 (11.9) 100.0 % 4.40 [ 0.14, 8.66 ]
Subtotal (95% CI)

47
46
100.0 %
4.40 [ 0.14, 8.66 ]
Test for overall effect: Z = 2.02 (P = 0.043) 2 vs psychotherapy and antipsychotic drugs May 1968 47 41.9 (8.8) 44 48 (6.3) 100.0 % -6.10 [ -9.23, -2.97 ]
Subtotal (95% CI)

47
44
100.0 %
-6.10 [ -9.23, -2.97 ]
-10
-5
10
favours control
favours treatment
97
Analysis 3.6. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 6 Leaving the study early.
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 6 Leaving the study early
Study or subgroup
Treatment n/N
Control n/N
Weight
1 short-medium term - vs psychotherapy alone May 1968 4/51 3/49 100.0 % 1.28 [ 0.30, 5.43 ]
Subtotal (95% CI)

51
49
100.0 %
1.28 [ 0.30, 5.43 ]
2 short-medium term - vs psychotherapy and antipsychotic drugs May 1968 4/51 5/49 100.0 % 0.77 [ 0.22, 2.70 ]
Subtotal (95% CI)

51
49
100.0 %
0.77 [ 0.22, 2.70 ]
3 long term (5 years) - vs psychotherapy alone May 1968 37/51 37/49 100.0 % 0.96 [ 0.76, 1.21 ]
Subtotal (95% CI)

51
49
100.0 %
0.96 [ 0.76, 1.21 ]
4 long term (5 years) - vs psychotherapy and antipsychotic drugs May 1968 37/51 39/49 100.0 % 0.91 [ 0.73, 1.14 ]
Subtotal (95% CI)

51
49
100.0 %
0.91 [ 0.73, 1.14 ]
0.1 0.2
0.5
10
favours treatment
favours control
98
Analysis 3.7. Comparison 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS, Outcome 7 Death - within three years after treatment.
Comparison: 3 ECT versus PSYCHOTHERAPY with or without ANTIPSYCHOTIC DRUGS Outcome: 7 Death - within three years after treatment
Study or subgroup
Treatment n/N
Control n/N 1/98
Weight
May 1968
0/51
100.0 %
0.63 [ 0.03, 15.31 ]
Total (95% CI)

51
98
100.0 %
0.63 [ 0.03, 15.31 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
Analysis 4.1. Comparison 4 ECT versus INSULIN COMA THERAPY, Outcome 1 Global impression: Not improved - at end of course of ECT.
Comparison: 4 ECT versus INSULIN COMA THERAPY Outcome: 1 Global impression: Not improved - at end of course of ECT
Study or subgroup
ECT n/N
Insulin coma n/N 6/15
Weight
Baker 1958
5/18
100.0 %
0.69 [ 0.26, 1.83 ]
Total (95% CI)

18
15
100.0 %
0.69 [ 0.26, 1.83 ]
Total events: 5 (ECT), 6 (Insulin coma) Test for overall effect: Z = 0.74 (P = 0.46)
0.1 0.2
0.5
10
favours ECT
favours insulin coma
99
Analysis 4.2. Comparison 4 ECT versus INSULIN COMA THERAPY, Outcome 2 Leaving the study early.
Comparison: 4 ECT versus INSULIN COMA THERAPY Outcome: 2 Leaving the study early
Study or subgroup
ECT n/N
Weight
Baker 1958
1/18
100.0 %
0.28 [ 0.03, 2.40 ]
Total (95% CI)

18
15
100.0 %
0.28 [ 0.03, 2.40 ]
0.1 0.2
0.5
10
favours ECT
Analysis 4.3. Comparison 4 ECT versus INSULIN COMA THERAPY, Outcome 3 Relapse.
Comparison: 4 ECT versus INSULIN COMA THERAPY Outcome: 3 Relapse
Study or subgroup
ECT n/N
Weight
Baker 1958
4/18
100.0 %
0.67 [ 0.22, 2.05 ]
Total (95% CI)

18
15
100.0 %
0.67 [ 0.22, 2.05 ]
0.1 0.2
0.5
10
favours ECT
100
Analysis 5.1. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 1 Global impression: 1. Average endpoint score (GAF, high scores = good).
Comparison: 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS Outcome: 1 Global impression: 1. Average endpoint score (GAF, high scores = good)
Study or subgroup
Control N Mean(SD)
Weight
1 CECT vs antipsychotic drugs Chanpattana 1999a 15 30.76 (5.51) 15 32 (8.49) 100.0 % -1.24 [ -6.36, 3.88 ]
Subtotal (95% CI)

15
15
100.0 %
-1.24 [ -6.36, 3.88 ]
Test for overall effect: Z = 0.47 (P = 0.64) 2 CECT vs CECT + antipsychotics Chanpattana 1999a 15 30.76 (5.51) 15 51.06 (16.54) 100.0 % -20.30 [ -29.12, -11.48 ]
Subtotal (95% CI)

15
15
100.0 % -20.30 [ -29.12, -11.48 ]
Test for overall effect: Z = 4.51 (P < 0.00001) 3 CECT + antipsychotics vs antipsychotics Chanpattana 1999a 15 51.06 (16.54) 15 32 (8.49) 100.0 % 19.06 [ 9.65, 28.47 ]
Subtotal (95% CI)

15
15
100.0 %
19.06 [ 9.65, 28.47 ]
-100
-50
50
100
Favours control
Favours treatment
101
Analysis 5.2. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 2 Global impression: 2. Relapse.
Comparison: 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS Outcome: 2 Global impression: 2. Relapse
Study or subgroup
Treatment n/N
Control n/N
Weight
1 CECT vs antipsychotic drugs Chanpattana 1999a 14/15 14/15 100.0 % 1.00 [ 0.83, 1.21 ]
Subtotal (95% CI)

Total events: 14 (Treatment), 14 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 CECT + antipsychotics vs CECT Chanpattana 1999a
15
15
100.0 %
1.00 [ 0.83, 1.21 ]
6/15
14/15
100.0 %
0.43 [ 0.23, 0.81 ]
Subtotal (95% CI)

15
15
100.0 %
0.43 [ 0.23, 0.81 ]
Test for overall effect: Z = 2.62 (P = 0.0089) 3 CECT + antipsychotics vs antipsychotics Chanpattana 1999a 6/15 14/15 100.0 % 0.43 [ 0.23, 0.81 ]
Subtotal (95% CI)

15
15
100.0 %
0.43 [ 0.23, 0.81 ]
Test for overall effect: Z = 2.62 (P = 0.0089)
0.01
0.1
10
100
Favours treatment
Favours control
102
Analysis 5.3. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 3 Mental state: Average endpoint score ( BPRS, high scores = poor).
Comparison: 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS Outcome: 3 Mental state: Average endpoint score ( BPRS, high scores = poor)
Study or subgroup
Control N Mean(SD)
Weight
1 CECT vs antipsychotic drugs Chanpattana 1999a 15 41.12 (10.46) 15 42.75 (10.32) 100.0 % -1.63 [ -9.07, 5.81 ]
Subtotal (95% CI)

15
15
100.0 %
-1.63 [ -9.07, 5.81 ]
Test for overall effect: Z = 0.43 (P = 0.67) 2 CECT vs CECT + antipsychotic drugs Chanpattana 1999a 15 41.12 (10.46) 15 23 (15.62) 100.0 % 18.12 [ 8.61, 27.63 ]
Subtotal (95% CI)

15
15
100.0 %
18.12 [ 8.61, 27.63 ]
Test for overall effect: Z = 3.73 (P = 0.00019) 3 CECT + antipsychotics vs antipsychotic drugs Chanpattana 1999a 15 23 (15.62) 15 42.75 (10.32) 100.0 % -19.75 [ -29.22, -10.28 ]
Subtotal (95% CI)

15
15
100.0 % -19.75 [ -29.22, -10.28 ]
-100
-50
50
100
Favours treatment
Favours control
103
Analysis 5.4. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 4 Leaving study early.
Comparison: 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS Outcome: 4 Leaving study early
Study or subgroup
Treatment n/N
Control n/N
Weight
1 CECT vs antipsychotics Chanpattana 1999a 1/15 3/15 100.0 % 0.33 [ 0.04, 2.85 ]
Subtotal (95% CI)

Total events: 1 (Treatment), 3 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.00 (P = 0.32) 2 CECT + antipsychotics vs CECT Chanpattana 1999a
15
15
100.0 %
0.33 [ 0.04, 2.85 ]
2/15
1/15
100.0 %
2.00 [ 0.20, 19.78 ]
Subtotal (95% CI)

Total events: 2 (Treatment), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.59 (P = 0.55) 3 CECT + antipsychotics vs antipsychotics Chanpattana 1999a
15
15
100.0 %
2.00 [ 0.20, 19.78 ]
2/15
3/15
100.0 %
0.67 [ 0.13, 3.44 ]
Subtotal (95% CI)

15
15
100.0 %
0.67 [ 0.13, 3.44 ]
0.01
0.1
10
100
Favours treatment
Favours control
104
Analysis 5.5. Comparison 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS, Outcome 5 Adverse effects - cognitive: Average endpoint score (MMSE, high scores = good).
Comparison: 5 CONTINUATION ECT versus ANTIPSYCHOTIC DRUGS Outcome: 5 Adverse effects - cognitive: Average endpoint score (MMSE, high scores = good)
Study or subgroup
Control N Mean(SD)
Weight
1 CECT vs antipsychotic drugs Chanpattana 1999a 15 25.29 (4.69) 15 25.25 (4.74) 100.0 % 0.04 [ -3.33, 3.41 ]
Subtotal (95% CI)

15
15
100.0 %
0.04 [ -3.33, 3.41 ]
Test for overall effect: Z = 0.02 (P = 0.98) 2 CECT vs CECT + antipsychotic drugs Chanpattana 1999a 15 25.29 (4.69) 15 27.61 (3.5) 100.0 % -2.32 [ -5.28, 0.64 ]
Subtotal (95% CI)

15
15
100.0 %
-2.32 [ -5.28, 0.64 ]
Test for overall effect: Z = 1.54 (P = 0.12) 3 CECT + antipsychotics vs antipsychotic drugs Chanpattana 1999a 15 27.61 (3.5) 15 25.25 (4.74) 100.0 % 2.36 [ -0.62, 5.34 ]
Subtotal (95% CI)

15
15
100.0 %
2.36 [ -0.62, 5.34 ]
-10
-5
10
Favours control
Favours treatment
105
Analysis 6.1. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 1 Global impression: 1. Not improved.
Comparison: 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT Outcome: 1 Global impression: 1. Not improved
Study or subgroup
Unilateral ECT n/N
Bilateral ECT n/N
Weight
1 mid-course ECT Doongaji 1973 Sarita 1998 10/35 6/12 6/19 5/12 60.9 % 39.1 % 0.90 [ 0.39, 2.10 ] 1.20 [ 0.50, 2.88 ]
Subtotal (95% CI)
47
31
100.0 %
1.02 [ 0.55, 1.88 ]
Total events: 16 (Unilateral ECT), 11 (Bilateral ECT) Heterogeneity: Chi2 = 0.21, df = 1 (P = 0.65); I2 =0.0% Test for overall effect: Z = 0.06 (P = 0.95) 2 end of course of ECT Doongaji 1973 Sarita 1998 11/35 5/12 7/19 7/12 56.5 % 43.5 % 0.85 [ 0.40, 1.83 ] 0.71 [ 0.31, 1.63 ]
Subtotal (95% CI)
47
31
100.0 %
0.79 [ 0.45, 1.39 ]
Total events: 16 (Unilateral ECT), 14 (Bilateral ECT) Heterogeneity: Chi2 = 0.10, df = 1 (P = 0.76); I2 =0.0% Test for overall effect: Z = 0.81 (P = 0.42) 3 medium term (12 weeks) Doongaji 1973 14/35 11/19 100.0 % 0.69 [ 0.40, 1.21 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.30 (P = 0.19)
35
19
100.0 %
0.69 [ 0.40, 1.21 ]
Total events: 14 (Unilateral ECT), 11 (Bilateral ECT)
0.1 0.2
0.5
10
Favours unilateral
favours bilateral
106
Analysis 6.2. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 2 Mental state: 1. Average endpoint score (BPRS, high = poor).
Comparison: 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT Outcome: 2 Mental state: 1. Average endpoint score (BPRS, high = poor)
Study or subgroup
Unilateral ECT N Mean(SD)
Bilateral ECT N Mean(SD)
Weight
1 mid-course ECT Doongaji 1973 17 24.9 (7.3) 19 24.9 (4.4) 100.0 % 0.0 [ -3.99, 3.99 ]
Subtotal (95% CI)

17
19
100.0 %
0.0 [ -3.99, 3.99 ]
Test for overall effect: Z = 0.0 (P = 1.0) 2 end of course of ECT Doongaji 1973 17 25.6 (10.6) 19 26.1 (7.5) 100.0 % -0.50 [ -6.56, 5.56 ]
Subtotal (95% CI)

17
19
100.0 % -0.50 [ -6.56, 5.56 ]
-10
-5
10
Favours unilateral
Favours bilateral
107
Analysis 6.3. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 3 Adverse effects: 1. Memory - at end of course of ECT.
Comparison: 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT Outcome: 3 Adverse effects: 1. Memory - at end of course of ECT
Study or subgroup
Unilateral ECT n/N
Bilateral ECT n/N
Weight
1 visual memory - impaired Bagadia 1988 8/20 6/20 100.0 % 1.33 [ 0.57, 3.14 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.66 (P = 0.51) 2 unaided recall - impaired Bagadia 1988
20
20
100.0 %
1.33 [ 0.57, 3.14 ]
3/20
5/20
100.0 %
0.60 [ 0.17, 2.18 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.78 (P = 0.44) 3 confabulation -present Bagadia 1988
20
20
100.0 %
0.60 [ 0.17, 2.18 ]
3/20
5/20
100.0 %
0.60 [ 0.17, 2.18 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.78 (P = 0.44) 4 subjective forgetfulness Bagadia 1988
20
20
100.0 %
0.60 [ 0.17, 2.18 ]
4/20
1/20
100.0 %
4.00 [ 0.49, 32.72 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.29 (P = 0.20)
20
20
100.0 %
4.00 [ 0.49, 32.72 ]
0.1 0.2
0.5
10
Favours unilateral
Favours bilateral
108
Analysis 6.4. Comparison 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT, Outcome 4 Adverse effects: 2. Memory - average end point score.
Comparison: 6 ECT - ELECTRODE PLACEMENT: UNILATERAL versus BILATERAL ECT Outcome: 4 Adverse effects: 2. Memory - average end point score
Study or subgroup
Unilateral ECT N Mean(SD)
Bilateral ECT N Mean(SD)
Weight
1 verbal memory ( paired associate learning, high scores = good) Sarita 1998 12 10.4 (3.9) 12 9.7 (4.7) 100.0 % 0.70 [ -2.76, 4.16 ]
Subtotal (95% CI)

12
12
100.0 %
0.70 [ -2.76, 4.16 ]
Test for overall effect: Z = 0.40 (P = 0.69) 2 visual memory (high scores = good) Sarita 1998 12 32.4 (9.1) 12 28.5 (12.7) 100.0 % 3.90 [ -4.94, 12.74 ]
Subtotal (95% CI)

12
12
100.0 % 3.90 [ -4.94, 12.74 ]
-10
-5
10
Favours unilateral
Favours bilateral
109
Analysis 7.1. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 1 Global impression: not improved.
Comparison: 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT Outcome: 1 Global impression: not improved
Study or subgroup
Treatment n/N
Control n/N
Weight
1 threshold ECT vs 2 times threshold ECT Chanpattana 2000 12/23 12/23 100.0 % 1.00 [ 0.58, 1.74 ]
Subtotal (95% CI)

Total events: 12 (Treatment), 12 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 threshold ECT vs 4 times threshold ECT Chanpattana 2000
23
23
100.0 %
1.00 [ 0.58, 1.74 ]
12/23
11/21
100.0 %
1.00 [ 0.57, 1.75 ]
Subtotal (95% CI)

23
21
100.0 %
1.00 [ 0.57, 1.75 ]
3 2 times threshold ECT vs 4 times threshold ECT Chanpattana 2000 12/23 11/21 100.0 % 1.00 [ 0.57, 1.75 ]
Subtotal (95% CI)

23
21
100.0 %
1.00 [ 0.57, 1.75 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
110
Analysis 7.2. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 2 Leaving study early.
Comparison: 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT Outcome: 2 Leaving study early
Study or subgroup
Treatment n/N
Control n/N
Weight
1 threshold ECT vs 2 times threshold ECT Chanpattana 2000 2/23 2/23 100.0 % 1.00 [ 0.15, 6.51 ]
Subtotal (95% CI)

Total events: 2 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 threshold ECT vs 4 times threshold ECT Chanpattana 2000
23
23
100.0 %
1.00 [ 0.15, 6.51 ]
2/23
1/21
100.0 %
1.83 [ 0.18, 18.70 ]
Subtotal (95% CI)

23
21
100.0 %
1.83 [ 0.18, 18.70 ]
3 2 times threshold ECT vs 4 times threshold ECT Chanpattana 2000 2/23 1/21 100.0 % 1.83 [ 0.18, 18.70 ]
Subtotal (95% CI)

23
21
100.0 %
1.83 [ 0.18, 18.70 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
111
Analysis 7.3. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 3 SUBGROUP of people in remission - Number of ECT treatments: 1. To rst improvement.
Comparison: 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT Outcome: 3 SUBGROUP of people in remission - Number of ECT treatments: 1. To rst improvement
Study or subgroup
Control N Mean(SD)
Weight
1 threshold ECT vs 2 times threshold ECT Chanpattana 2000 11 13.6 (5) 11 7.5 (3.8) 100.0 % 6.10 [ 2.39, 9.81 ]
Subtotal (95% CI)

11
11
100.0 %
6.10 [ 2.39, 9.81 ]
Test for overall effect: Z = 3.22 (P = 0.0013) 2 threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 13.6 (5) 11 4.2 (1.5) 100.0 % 9.40 [ 6.32, 12.48 ]
Subtotal (95% CI)

11
11
100.0 %
9.40 [ 6.32, 12.48 ]
Test for overall effect: Z = 5.97 (P < 0.00001) 3 2 times threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 7.43 (3.8) 11 4.2 (1.5) 100.0 % 3.23 [ 0.82, 5.64 ]
Subtotal (95% CI)

11
11
100.0 %
3.23 [ 0.82, 5.64 ]
-10
-5
10
Favours treatment
Favours control
112
Analysis 7.4. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 4 SUBGROUP of people in remission - Number ECT treatments: 2. At end of course of ECT.
Comparison: 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT Outcome: 4 SUBGROUP of people in remission - Number ECT treatments: 2. At end of course of ECT
Study or subgroup
Control N Mean(SD)
Weight
1 theshold ECT vs 2 times threshold ECT Chanpattana 2000 11 18.6 (5) 11 12.5 (3.8) 100.0 % 6.10 [ 2.39, 9.81 ]
Subtotal (95% CI)

11
11
100.0 %
6.10 [ 2.39, 9.81 ]
Test for overall effect: Z = 3.22 (P = 0.0013) 2 threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 18.6 (5) 11 9.2 (1.5) 100.0 % 9.40 [ 6.32, 12.48 ]
Subtotal (95% CI)

11
11
100.0 %
9.40 [ 6.32, 12.48 ]
Test for overall effect: Z = 5.97 (P < 0.00001) 3 2 times threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 12.5 (3.8) 11 9.2 (1.5) 100.0 % 3.30 [ 0.89, 5.71 ]
Subtotal (95% CI)

11
11
100.0 %
3.30 [ 0.89, 5.71 ]
-10
-5
10
Favours treatment
Favours control
113
Analysis 7.5. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 5 SUBGROUP of people in remission - Days of treatment: 1. To rst improvement.
Comparison: 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT Outcome: 5 SUBGROUP of people in remission - Days of treatment: 1. To rst improvement
Study or subgroup
Control N Mean(SD)
Weight
1 threshold ECT vs 2 times threshold ECT Chanpattana 2000 11 35.4 (16.3) 11 16.4 (11.9) 100.0 % 19.00 [ 7.07, 30.93 ]
Subtotal (95% CI)

11
11
100.0 %
19.00 [ 7.07, 30.93 ]
Test for overall effect: Z = 3.12 (P = 0.0018) 2 threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 35.4 (16.3) 11 7 (3.6) 100.0 % 28.40 [ 18.54, 38.26 ]
Subtotal (95% CI)

11
11
100.0 %
28.40 [ 18.54, 38.26 ]
Test for overall effect: Z = 5.64 (P < 0.00001) 3 2 times threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 16.4 (11.9) 11 7 (3.6) 100.0 % 9.40 [ 2.05, 16.75 ]
Subtotal (95% CI)

11
11
100.0 %
9.40 [ 2.05, 16.75 ]
-10
-5
10
Favours treatment
Favours control
114
Analysis 7.6. Comparison 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT, Outcome 6 SUBGROUP of people in remission - Days of treatment: 2. At end of course of ECT.
Comparison: 7 ECT - DOSE: THRESHOLD versus SUPRATHRESHOLD ECT Outcome: 6 SUBGROUP of people in remission - Days of treatment: 2. At end of course of ECT
Study or subgroup
Control N Mean(SD)
Weight
1 threshold ECT vs 2 times threshold ECT Chanpattana 2000 11 56.4 (16.3) 11 37.5 (12) 100.0 % 18.90 [ 6.94, 30.86 ]
Subtotal (95% CI)

11
11
100.0 %
18.90 [ 6.94, 30.86 ]
Test for overall effect: Z = 3.10 (P = 0.0020) 2 threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 56.4 (16.3) 11 37.5 (12) 100.0 % 18.90 [ 6.94, 30.86 ]
Subtotal (95% CI)

11
11
100.0 %
18.90 [ 6.94, 30.86 ]
Test for overall effect: Z = 3.10 (P = 0.0020) 3 2 times threshold ECT vs 4 times threshold ECT Chanpattana 2000 11 37.5 (12) 11 28 (3.6) 100.0 % 9.50 [ 2.10, 16.90 ]
Subtotal (95% CI)

11
11
100.0 %
9.50 [ 2.10, 16.90 ]
-10
-5
10
Favours treatment
Favours control
115
Analysis 8.1. Comparison 8 ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL), Outcome 1 Adverse effects: 1. Cognitve impairment clinically apparent.
Comparison: 8 ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL) Outcome: 1 Adverse effects: 1. Cognitve impairment clinically apparent
Study or subgroup
Treatment n/N
Control n/N 0/6
Abrams 1967
0/4
Total (95% CI)

0.0 [ 0.0, 0.0 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
Analysis 8.2. Comparison 8 ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL), Outcome 2 Adverse effects: 2. Memory - Average endpoint score (Weshler memory scale-form I, high score = good).
Comparison: 8 ECT - FREQUENCY: 3 DAYS/WEEK versus 5 DAYS/WEEK (UNILATERAL) Outcome: 2 Adverse effects: 2. Memory - Average endpoint score (Weshler memory scale-form I, high score = good)
Study or subgroup
Weight
Abrams 1967
100.0 %
2.97 [ -8.45, 14.39 ]
Total (95% CI)

100.0 %
2.97 [ -8.45, 14.39 ]
-10
-5
10
Favours control
Favours treatment
116
Analysis 9.1. Comparison 9 ECT - NUMBER OF TREATMENTS: 12 versus 20 TREATMENTS, Outcome 1 Global impression: Not improved.
Comparison: 9 ECT - NUMBER OF TREATMENTS: 12 versus 20 TREATMENTS Outcome: 1 Global impression: Not improved
Study or subgroup
Treatment n/N
Control n/N 5/19
Weight
Baker 1960
16/24
100.0 %
2.53 [ 1.13, 5.66 ]
Total (95% CI)

24
19
100.0 %
2.53 [ 1.13, 5.66 ]
0.1 0.2
0.5
10
Favours treatment
Favours control
ADDITIONAL TABLES
Table 1. ECT versus SHAM ECT: Global impression: Adjustment (KAS, high=good, medium t
Study Sarkar 1994
ECT mean (SD) 11.0 (7.7)
N 15
Sham mean (SD) 11.3 (8.0)
N 15
Table 2. ECT versus SHAM ECT: Global psychopathology: percentage change (VAS, high = poor
Period Mid-course
Study Brandon 1985
ECT mean (SD) 47 (10.4)
N 9
Sham mean (SD) 80.0 (2.5)
N 8
At end of course
Brandon 1985
41 (12.7)
69 (9.9)
Medium term
Brandon 1985
48 (7.8)
43 (7.8)
Long term
Brandon 1985
46 (7.0)
39 (10.4)
117
Table 3. ECT versus SHAM ECT: Mental State: 1. Average change (BPRS, high = poor) Period Mid course Study Ukpong 2002 ECT mean (SD) 6.6 (6.2) N 9 Placebo mean (SD) 8.3 (5.5) N 7
At end of course
Sarita 1998 Sarkar 1994 Ukpong 2002
17.0 (18.4) 8.1 (5.1) 3.7 (4.2)
12 15 9
14.7 (16.2) 8.7 (4.5) 4.1 (3.9)
12 15 7
Short term
Ukpong 2002
1.1 (1.7)
1.4 (1.8)
Medium term
Sarkar 1994 Ukpong 2002
1.8 (2.1) 1.0 (3.0)
15 9
3.6 (3.9) 1.3 (3.4)
15 7
Table 4. ECT versus SHAM ECT: Mental State: 2. percentage change (MASS, high = poor)
Period Mid ECT course
Study Brandon 1985
ECT mean (SD) 3 (1.3)
N 9
Sham mean (SD) 8 (1.4)
N 8
End of ECT course
Brandon 1985
3 (1.2)
9 (1.8)
Medium term
Brandon 1985
4 (1.6)
3 (1.0)
Long term
Brandon 1985
3 (1.1)
4 (1.3)
Table 5. ECT versus SHAM ECT: Depression: 1. percentage change: (Visual analogue, high=p
Period Mid course ECT
Study Brandon 1985
N 9
Sham ECT mean (SD) 67 (5.6)
N 8
118
Table 5. ECT versus SHAM ECT: Depression: 1. percentage change: (Visual analogue, high=p
(Continued)
Enof ECT course
Brandon 1985
54 (6.2)
71 (6.4)
Medium term
Brandon 1985
60 (3.2)
48 (8.3)
Long term
Brandon 1985
57 (2.4)
57 (3.2)
Table 6. ECT versus SHAM ECT: Depression: 2. percentage change: (HDRS, high = poor)
Period Mid course ECT
Study Brandon 1985
N 9
Sham ECT mean (SD) 27 (5.2)
N 8
End of ECT course
Brandon 1985
17 (5.1)
25 (6.5)
Medium term
Brandon 1985
60 (3.2)
48 (8.3)
Long term
Brandon 1985
57 (2.4)
57 (3.2)
Table 7. ECT versus PLACEBO: Employment -2 years (proportion)
Study May 1968
ECT mean (SD) 1.7 (1.9)
N 47
Placebo mean (SD) 1.6 (1.7)
N 42
Table 8. ECT versus SHAM ECT: Adverse effects: 2. Extrapyramidal (UKU, high = poor)
Study Sarita 1998
ECT mean (SD) 1.5 (1.7)
N 12
Sham ECT mean (SD) 1.2 (1.7)
N 12
119
Table 9. UNILATERAL versus BILATERAL ECT: Adverse effects: 1. Verbal memory (high = good
Study Sarita 1998
UNILAT ECT mean (SD) N 32.7 (19.2) 12
BILAT ECT mean (SD) 2.7 (14.2)
N 12
Table 10. ECT and PLACEBO vs ANTIPSYCHOTIC and SECT. Global imp: 1. Ave (BFCRS- hig
Period mid-course
Study Girish 2003
Mean (SD) 3.88 (3.52)
N 8
Mean (SD) 7.67 (3.61)
N 6
at end of course
Girish 2003
0.62 (1.18)
6.16 (4.75)
WHATS NEW
Last assessed as up-to-date: 15 February 2005.
Date 5 August 2009
Event Amended
Description Contact details updated.
HISTORY
Protocol rst published: Issue 1, 1996 Review rst published: Issue 2, 1997
Date 23 April 2008 16 February 2005
Event Amended New citation required and conclusions have changed
Description Converted to new review format. Substantive amendment
120
CONTRIBUTIONS OF AUTHORS
Prathap Tharyan - thought of the review, wrote the protocol, selected the studies, extracted data, undertook the analyses, wrote the nal report and maintains and updates the review. Clive Adams - helped extract data, undertake the analyses, write the nal report and maintain the review.
DECLARATIONS OF INTEREST
None known.
SOURCES OF SUPPORT Internal sources

Christian Medical College, Vellore, India.
External sources
Cochrane Schizophrenia Group General Fund, UK.
NOTES
This review won the Ken Warren Prize in 2002 for the best Cochrane review from a reviewer resident in a developing country.
INDEX TERMS Medical Subject Headings (MeSH)
Electroconvulsive Therapy; Randomized Controlled Trials as Topic; Schizophrenia [ therapy]
MeSH check words

Humans
121

ECT For Schizophrenia

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ECT For Schizophrenia

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Electroconvulsive therapy for schizophrenia (Review)

Electroconvulsive therapy for schizophrenia

Criteria for considering studies for this review

Types of studies We included all relevant randomised controlled trials.

Data collection and analysis

Search methods for identication of studies

Risk of bias in included studies

AUTHORS CONCLUSIONS Implications for practice

Implications for research

References to studies included in this review

References to studies excluded from this review

References to studies awaiting assessment

References to ongoing studies

Characteristics of included studies [ordered by study ID]

Authors judgement Unclear

Notes Risk of bias Item Allocation concealment? Bagadia 1988 Methods

Authors judgement Unclear

Authors judgement Unclear

Item Allocation concealment? Brandon 1985 Methods

Authors judgement Unclear

Notes Risk of bias Item Allocation concealment? Brill 1959 Methods

Authors judgement Unclear

Authors judgement Unclear

Item Allocation concealment?

Authors judgement Yes

Authors judgement Unclear

Notes Risk of bias Item Allocation concealment? Sarita 1998 Methods

Authors judgement Unclear

Notes Risk of bias Item Allocation concealment? Sarkar 1994 Methods

Authors judgement Unclear

Notes Risk of bias Item Allocation concealment?

Authors judgement Yes

Authors judgement Unclear

Characteristics of excluded studies [ordered by study ID]

Chanpattana 1999e Chanpattana 2000b Chanpattana 2000c Chanpattana 2002

Dodwell 1989 Early 1999

Gottlieb 1951 Green 1994 Greenblatt 1962

Gujavarty 1987 Guo 2000 Hargreaves 1972 He 2001

King 1960 Klapheke 1999 Konig 1990

Kupchik 2000 Landy 1991 Langsley 1959

Laurell 1970a Laurell 1970b Levin 1990

Lewis 1982 Li 2002 Ligthart 1956 Lingl 1964 Lui 1993

Mezquita 1973 Milstein 1990 Murillo 1973 Natani 1983

Ostzovscki 1997 Ottosson 1960 Petrides 1996

Rhode 1961 Safferman 1992 Sajatovic 1993 Small 1968

Smith 1967 Stenback 1957

Weinstein 1971 Wessels 1972 West 1982

Xie 1994 Xue 1985

Characteristics of ongoing studies [ordered by study ID]

Outcomes Starting date

DATA AND ANALYSES

Comparison 1. ECT versus PLACEBO or SHAM ECT

Statistical method Risk Ratio (M-H, Fixed, 95% CI)

-1.80 [-6.57, 2.97] 1.30 [-3.31, 5.91] Subtotals only

Mean Difference (IV, Fixed, 95% CI)

4.10 [-0.40, 8.60]

Mean Difference (IV, Fixed, 95% CI)

-3.10 [-6.59, 0.39]

Statistical method Risk Ratio (M-H, Fixed, 95% CI)

Effect size Subtotals only

2.18 [1.31, 3.63] 1.10 [0.74, 1.63] 1.15 [0.73, 1.82]

Risk Ratio (M-H, Fixed, 95% CI)