Summary01 PDF

Electroconvulsive therapy for depression
Till min familj
rebro Studies in Medicine 85
AXEL NORDENSKJLD
Electroconvulsive therapy for depression
Axel Nordenskjld, 2013

Title: Electroconvulsive therapy for depression
Publisher: rebro University 2013
www.publications.oru.se
trycksaker@oru.se
Print: Ineko, Kllered 04/2013
ISSN 1652-4063
ISBN 978-91-7668-932-5
Abstract
Axel Nordenskjld (2013): Electroconvulsive therapy for depression. rebro
Studies in Medicine 85, 89 pp.
Aim: The overarching aims of the thesis were to identify clinical
characteristics that predict the outcomes of depressed patients treated in
clinical practice by ECT, and to elucidate the effectiveness of continuation
ECT at preventing relapses and recurrences.
Methods: The studies included a retrospective chart review, three studies
based on a quality register for ECT, and a randomized controlled trial
(RCT) examining the effectiveness of continued ECT.
Results: The overall response rate to ECT was 80%. Patients with psychotic depression (89%), older patients (84%), and inpatients (83%) had
the highest response rates. Patients with personality disorders (66%) and
outpatients (66%) had the lowest response rates. With regard to patients
on sick leave, 59%, 71% and 88% of patients regained occupational
functioning 6, 12 and 24 months after ECT, respectively.
The rate of hospitalisation after ECT was high, with rates of 25%, 34%
and 44% 6, 12 and 24 months after ECT, respectively. The relapse rate
was higher in patients that were taking benzodiazepines and lower in patients that were taking lithium.
The relapse rate was significantly lower in patients treated with continued
ECT in combination with pharmacotherapy (32%) than in those treated
with pharmacotherapy alone (61%). This difference was particularly pronounced in medication-resistant patients (31% vs. 85%)
Conclusions: The short-term response rate to ECT is relatively high in all
patient subgroups, and is particularly high in older patients, inpatients and
patients with severe depression. Patients often regain occupational functioning after ECT; however, this takes a considerably longer time than that
required for symptom relief. Nevertheless, the relapse and recurrence rates
of patients are high in the years after ECT. Continuation ECT and lithium
treatment can be combined with antidepressants to reduce the risk of relapse and recurrence. Further RCTs are required to define the indications
for continuation ECT and lithium treatment.
Keywords: Electroconvulsive therapy; Mood disorders; Depressive disorder,
major; Bipolar disorder; Treatment outcome; Recurrence
Axel Nordenskjld, School of Health and Medical Sciences
rebro University, SE-701 82 rebro, Sweden,
axel.nordenskjold@orebroll.se
LIST OF PAPERS
This thesis is based on the following original papers:
I. Nordenskjld A, von Knorring L, Engstrm I. Predictors of the
short-term responder rate of Electroconvulsive therapy in depressive disorders -a population based study. BMC Psychiatry. 2012
Aug 17;12:115.
II. Nordenskjld A, von Knorring L, Engstrm I. Predictors of time

to relapse/recurrence after electroconvulsive therapy in patients
with major depressive disorder: a population-based cohort study.
Depress Res Treat. 2011;2011:470985. Epub 2011 Nov 3.
III. Nordenskjld A, von Knorring L, Ljung T, Carlborg A, Brus O,

Engstrm I. Continuation electroconvulsive therapy with pharmacotherapy versus pharmacotherapy alone for prevention of relapse
of depression: a randomized controlled trial. J ECT. 2013 Jan 8
Epub ahead of print
IV. Nordenskjld A, von Knorring L, Engstrm I. Rehospitalization

rate after continued electroconvulsive therapy-a retrospective chart
review of patients with severe depression. Nord J Psychiatry. 2011
Feb; 65(1) :26-31. Epub 2010 May 20.
V. Nordenskjld A, von Knorring L, Brus O, Engstrm I. Predictors

of regained occupational functioning after electroconvulsive therapy (ECT) in patients with major depressive disorder-a population
based cohort study. Nord J Psychiatry. 2012 Dec 11 Epub ahead
of print
The indicated Roman numerals are used throughout the text to reference
these studies. Reprints were made with the permission of the publishers.
CONTENTS
LIST OF ABBREVIATIONS .................................................................... 13
DEFINITIONS......................................................................................... 15
INTRODUCTION................................................................................... 17
BACKGROUND...................................................................................... 19
Mood disorders........................................................................................ 19
Depressive episode ............................................................................... 19
Pathophysiology of depression ............................................................. 20
Epidemiology of depression ................................................................. 21
Course of depression............................................................................ 21
Mortality in depression ........................................................................ 22
Depression and co-morbidity ............................................................... 22
Cognitive effects of depression ............................................................. 22
Depression and occupational functioning ............................................ 22
Treatment of depression....................................................................... 23
Electroconvulsive therapy ........................................................................ 24
History of ECT .................................................................................... 24
Mode of action of ECT ........................................................................ 25
ECT administration ............................................................................. 25
Indications for ECT ............................................................................. 27
ECT worldwide.................................................................................... 28
Effectiveness of ECT ............................................................................ 28
Predictors of the short-term effectiveness of ECT................................. 29
Cognitive effects of ECT ...................................................................... 29
Common side effects and complications of ECT .................................. 31
Serious complications related to ECT .................................................. 32
Stigma associated with ECT................................................................. 32
Ethics of ECT....................................................................................... 32
Relapse after ECT ................................................................................ 33
Continuation ECT to prevent relapse after index ECT ........................ 33
Summary and scope for the empirical studies........................................... 34
AIMS ....................................................................................................... 35
METHODS.............................................................................................. 37
Methods used in the separate studies ................................................... 41
Patients included in the separate studies............................................... 41
Quality register for ECT ...................................................................... 41
Rating scales ........................................................................................ 42
Statistical analysis ................................................................................ 43

ECT ..................................................................................................... 43
Pharmacotherapies ............................................................................... 44
Study I.................................................................................................. 44
Design .............................................................................................. 44
Patients ............................................................................................ 44
Outcome measure ............................................................................ 44
Study II ................................................................................................ 44
Design .............................................................................................. 44
Patients ............................................................................................ 44
Follow-up ........................................................................................ 44
Outcome measure ............................................................................ 45
Study III ............................................................................................... 45
Design .............................................................................................. 45
Patients ............................................................................................ 45
Randomisation................................................................................. 45
Interventions .................................................................................... 46
Follow-up ........................................................................................ 47
Sample size....................................................................................... 47
Outcome measure ............................................................................ 47
Study IV ............................................................................................... 47
Design .............................................................................................. 47
Patients ............................................................................................ 47
Continuation ECT ........................................................................... 47
Pharmacotherapies........................................................................... 48
Outcome measure ............................................................................ 48
Study V ................................................................................................ 48
Design .............................................................................................. 48
Patients ............................................................................................ 48
Outcome measure ............................................................................ 48
Ethical considerations .............................................................................. 49
RESULTS ................................................................................................. 51
Response to ECT (study I)........................................................................ 52
Hospitalisation after ECT (study II) ......................................................... 53
Efficacy of continuation ECT (study III) .................................................. 55
Relapse in the intention-to-treat sample ............................................... 56
Relapse in post hoc subgroups ............................................................. 56
Cognitive functions .............................................................................. 56
Hospitalisation relative to continuation ECT (study IV) .......................... 57
Time to regain occupational functioning after ECT (study V).................. 57
DISCUSSION........................................................................................... 59
Methodological considerations ................................................................ 61
Scientific implications............................................................................... 64
Clinical implications................................................................................. 65
SAMMANFATTNING P SVENSKA (SUMMARY IN SWEDISH) ....... 69
ACKNOWLEDGEMENTS...................................................................... 71
REFERENCES ......................................................................................... 75
LIST OF ABBREVIATIONS
ADAS-cog
APA
The cognitive subscale of the Alzheimer's Disease

Assessment Scale
American Psychiatric Association
cECT
Continuation ECT
CGI-I
Clinical Global Impression-Improvement
DSM-IV TR
ECT
Diagnostic and Statistical manual of Mental disorders IV edition Text Revision

Electroconvulsive Therapy
EEG
Electroencephalography
HDQ
Hospital Day Quotient
ICD-10
International Classifications of Diseases 10th edition
MADRS
Montgomery sberg Depression Rating Scale
MINI
Mini-International Neuropsychiatric Interview
MMSE
MiniMental State Examination
NICE
National Institute for Clinical Excellence
SD
Standard Deviation
SNRI
Serotonin Nor-epinephrine Reuptake Inhibitor
SSRI
Selective Serotonin Reuptake Inhibitor
UKU
Utvalg for Kliniske Undersgelser
AXEL NORDENSKJLD Electroconvulsive therapy for depression
13
14
I AXEL NORDENSKJLD Electroconvulsive therapy for depression
DEFINITIONS
Continuation ECT: Weekly or monthly ECT sessions used to maintain the
benefits from the index ECT series. Sometimes the term maintenance ECT
is used to describe continuation ECT that occurs for longer than six
months. However, in this thesis, the term continuation ECT is used even
when the period extends beyond six months.
Hospital Day Quotient (HDQ): The total number of days spent in hospital
(HD) divided by product of the number of patients (P) and the number of
days in the period investigated (Dp) and then multiplied by 365.
HDQ=HD/(P Dp) 365
Index ECT: An acute series of ECT that is usually administered two or
three times per week. Daily treatments are occasionally used for very severe
cases. The treatment is prolonged until remission or until further benefits
are unlikely.
Non-response was defined as Clinical Global Impression-Improvement
score of greater than 2 (much improved). This included patients that were
minimally improved, were not changed, or worsened, and was assessed
within one week after ECT.
Outpatients: Patients who had at least one ECT session administered in an
outpatient setting. Thus, if the treatment was initiated in an inpatient setting and continued in an outpatient setting, the patient was considered to
be an outpatient in the statistical analyses.
Pharmacotherapy resistant patients: Patients who did not improve during
two adequate trials of different classes of antidepressants during an episode
of depression (122).
Relapse: In study III, relapse was defined as a score of 20 or more on the
Montgomery sberg Depression Rating Scale, or hospitalisation, or suspected suicide, or suicide. In study II, hospitalisation or committed suicide
was used as a proxy for relapse.
Recurrence: Symptoms reoccurred after a period of at least six months of
remission.
15
Remission: A score of 10 or less on the Montgomery sberg Depression

Rating Scale.
Response: A common definition of response is a 50 % reduction in a rating
scale of depression. However, in the empirical studies presented in this
thesis, response was defined as having a Clinical Global ImpressionImprovement score of 1 or 2 (very much improved or much improved)
within one week of ECT.
Severity of depression: Assessed by the physician in charge according to
ICD-10 as mild/moderate, severe without psychosis, or severe with psychosis. A corresponding severity classification was used for patients with
schizoaffective disorders, depressed type.
Voluntary/involuntary hospital admission: Assessed based on the legal
status of the patient. (In Sweden, verbal consent to ECT is standard but the
psychiatrist in charge can arrange for ECT without consent during involuntary care. Some voluntarily hospitalised patients may recognise that they
are required to accept ECT or else they risk involuntary care. Some involuntarily hospitalised patients may consent to ECT.)
16
INTRODUCTION
I would like to share a personal anecdote that contributed to my continuing interest in electroconvulsive therapy (ECT). One of the patients I met
early during my time in the psychosis department had been in compulsory
inpatient care for more than one year. The patient did not speak, laid on
the floor for several hours each day with a pillow over her head and occasionally started shouting and waving her arms. She had an earlier diagnosis
of bipolar disorder, but her current diagnosis was psychosis. Several
hospitalisations had been necessary after lithium treatment had been terminated due to a reduction in renal capacity. In the previous year, antidepressant medications and intramuscular antipsychotics were administered,
but the patients status was deteriorating. The situation became urgent
when the patient stopped eating and drinking. ECT was recommended for
psychotic depression with catatonia. The patient fiercely resisted and had
to be escorted by four persons to the ECT treatment. After the first treatment, the patient was calm, started to eat and drink, and slept for more
than twelve hours. The patient cooperated fully during the following
treatments. Within two weeks she had completely recovered. Afterwards,
the patient and her family were very grateful for the ECT and for being
able to celebrate Christmas together.
While serving in the depression ward I became aware of the effectiveness of
an acute series of ECT (index ECT), but also realised that many of the
patients treated with index ECT were readmitted within a few months of
discharge. There were discussions in the clinic about whether continuation
of ECT after discharge (continuation ECT) would be effective at preventing
relapse/recurrence. However, at that time there were no randomised studies
into the efficacy of continuation ECT, and it was difficult to reach a consensus among psychiatrists about the use of continuation ECT.
This thesis is concerned with the patient characteristics that are related to
the reduction of symptoms, relapse/recurrence and the return to occupational functioning after index ECT for major depression, and to the efficacy of continuation ECT combined with pharmacotherapy at preventing
relapse/recurrence. A prospective randomised trial, three studies of data
contained in the quality register for ECT and one chart review form the
basis of this thesis, and the discussion is primarily focused on the clinical
implications of the results.
17
18
BACKGROUND
The background section consists of two parts: a general introduction to
depression and a review of ECT.
Mood disorders
Mood disorders are classified by both the World Health Organisation International Classifications of Diseases 10th edition (ICD 10) (170) and the
Diagnostic and Statistical Manual of Mental Disorders IV Text Revision
(DSM IV TR) (2) into the following main categories:
- Major depressive episode (the first episode in a lifetime);
- Recurrent depression (after at least one earlier lifetime episode);
- Bipolar disorder (if the clinical history also includes at least one manic
or hypomanic episode);
- Schizoaffective disorder (if the patient has also had psychotic symptoms that are not related to an affective episode).
Depressive episode
A depressive episode can occur in any of these mood disorders. According
to the DSM-IV TR, a major depressive episode is diagnosed if five or more
of the following symptoms, including at least one of depressed mood or
loss of interest or pleasure, occurred during the same two weeks period and
represented a change from previous functioning:
1. Depressed mood most of the day, nearly every day, as indicated by
either subjective report (e.g., feels sad or empty) or observation
made by others (e.g., appears tearful).
2. Markedly diminished interest or pleasure in all, or almost all activities, nearly every day;
3. Significant weight loss when not dieting or weight gain (e.g., a
change of more than 5 % of body weight in a month), or decrease
or increase in appetite nearly every day;
4. Insomnia or hypersomnia nearly every day;
5. Psychomotor agitation or retardation nearly every day;
6. Fatigue or loss of energy nearly every day;
7. Feelings of worthlessness or excessive or inappropriate guilt nearly
every day;
8. Diminished ability to think or concentrate, or indecisiveness, (either
by subjective account or as observed by others), nearly every day;
19
9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide;
There are four additional criteria for a major depressive episode:
- The symptoms do not meet criteria for a mixed episode;
- The symptoms cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning;
- The symptoms are not due to the direct physiological effects of a substance or a general medical condition;
- The symptoms are not better accounted for by bereavement.
The definition according to ICD-10 is similar. A major depressive episode
can be classified as mild, moderate, severe, or severe with psychosis. In the
DSM IV-TR classification, the depressive episodes can be further subtyped
into melancholic, catatonic, and atypical.
Pathophysiology of depression
The pathophysiology of depression is not fully understood. However, genetic factors, environmental factors, and the patients own actions can
contribute to depression (132). There is a genetic vulnerability to develop
depression, especially bipolar depression (79) and to a lesser extent recurrent depression (155). Many genes are involved in regulating mood, and
the mechanisms by which these different genes interact are currently being
explored. Depression can be caused by a stressful life. However, most people are not depressed even though stressful events are common. Environmental factors in childhood are linked to depression (71, 113), and the
abuse of alcohol, other substances, and certain medications can also increase the risk of depression (38). Protective factors for depression include
physical activity and social support (132).
The biological systems that are affected in depression include neurotransmitters, stress hormones, and neuronal plasticity (10, 132). The monoamine hypothesis (65) suggests that transmission of monoamines is reduced in
depression. Most currently available antidepressants were developed according to this hypothesis and function by inhibiting reuptake of serotonin
and/or noradrenaline (152). The stress response is also abnormal in individuals with severe depression. Cortisol production is usually increased, the
diurnal variations are reduced, and the feedback-mediated control of cortisol is disturbed (158). The turnover of brain cells is also linked to depres-
20
sion. In animal studies, antidepressant treatments such as ECT result in

increased cell replication in areas thought to be important for emotional
regulation such as the amygdala, hippocampus, gyrus cinguli, and prefrontal cortex (15, 74).
In addition, a patients actions in response to their symptoms can result in
a downward spiral that increases the severity of the disease. For example,
lack of interest and drive may contribute to low levels of engagement in
normal daily activities, which in turn increases sad feelings that occur due
to a reduction of pleasant and interesting tasks. The basis of Cognitive
Behavioural Therapy (CBT) is to alleviate symptoms through changing the
patients thinking and actions (9).
Epidemiology of depression
Depression entails suffering, work impairment and is a burden to kindred
(132). Depression is a common disease. The one month prevalence of major depression is estimated to be between 1.5 and 3 % (119), and the oneyear prevalence is estimated to be 8.6 % (60). Nearly half of all women
and a quarter of all men suffer a depressive episode at some time in their
life (120). This high prevalence makes depression one of the most common
diseases and causes of handicap world-wide (166).
Course of depression
The prognosis for depression is often unfavourable. Symptoms persist for
two years or more in up to 20 % of patients (55). Repeated relapses or
chronicity occur in 7080 % of patients, and approximately 10 % of affected individuals commit suicide (4). Thirty percent of patients who are
treated as inpatients require re-hospitalisation within one year of discharge
(50, 153). Greater numbers of depressive episodes tend to increase the risk
of subsequent relapses or recurrences in patients with major depression
(159), and larger numbers of remaining symptoms are correlated with increased risks of relapse or recurrence in several studies of patients treated
with pharmacotherapies (92, 159). There is also evidence that patients with
co-morbid conditions have an increased risk of relapse or recurrence (22,
49), and some studies associated the severity of depressive symptoms with
increased risk of relapse or recurrence (78). Psychological therapies and
prolonged pharmacotherapies may reduce the risk of symptom recurrence
(132, 134). However, if the patient suffers more than one episode of depression, the risk of relapse and recurrence remains high even with treatment (27). Moreover, although effective treatments are available, a large
proportion of patients with depression do not receive treatment (53). Fur-
21
thermore, compliance is poor as only about half of the patients who receive
pharmacotherapies actually take the drugs as prescribed (143).
Mortality in depression
There is excess mortality among depressed patients, both in different diseases and in accidents (99, 121). The risk of suicide is 1530 times higher
in individuals with depression than in the normal population (99). Suicide
also occurs in young patients. Therefore, depression-related suicide has a
major impact on years of life lost. Most depression-related suicides occur
in patients who are not adequately treated (39). The lifetime risk of committing suicide is about 15 % among patients who receive in-hospital
treatment for depression (51). The depression-related suicide rate in Sweden has decreased in recent years in correlation with increased access to
antidepressant medications (52). However, suicide remains one of the most
frequent causes of death for both men and women aged 1574 years in
Sweden as more than 1 000 suicides occur annually (150). More than half
of those who die from suicide suffer from depression (167, 172).
Depression and co-morbidity
It is common for patients with depression to also have other psychiatric
disorders. Data from the United States indicate that the most common comorbidities are anxiety disorders (57 %), alcohol-related disorders (25 %),
and personality disorders (44 %) (58, 59). Common genetic pathophysiology may underlie the high co-morbidity of anxiety disorders and depression (14).
Cognitive effects of depression
Depressive disorders can also negatively affect cognitive functioning (43),
especially during the symptomatic state (5). More specifically, there can be
effects on concentration and memory storage. Severe forms of depression
tend to have greater impacts on cognitive functioning and memory than
less severe forms of depression (76). The disturbance often persists during
euthymic phases (12), and a 10-year follow-up study found that the effects
are long lasting (135). Cognitive impairments contribute to poor occupational functioning (25).
Depression and occupational functioning
Depression is one of the most frequent causes of poor occupational functioning. Depression accounts for more than 10 % of all compensated sick
leave days in many countries, including Sweden (47, 162). A large proportion of the costs due to depression are related to poor occupational func-
22
tioning (144). Symptomatic improvements are related to improved occupational functioning (44), but it usually takes months to regain occupational
functioning after symptoms decrease (82).
Treatment of depression
Pharmacotherapies and psychological therapies, especially Cognitive Behavioural Therapies, are effective treatments for mild and moderate depression (133, 134). About one-third of patients who are exposed to one of
these treatments achieve remission, which means they become free of
symptoms. Another one-third of the patients respond to treatments (often
defined as a 50 % reduction in symptom severity), but have some residual
symptoms. The other one-third does not respond to treatments with durations of 612 weeks (33, 142). There are no major differences in the efficacies of different forms of treatments in mild and moderate depression, and
some studies suggest that there are no significant differences between active
medications and placebo treatments (32). However, in severe depression,
active medications are markedly more effective than placebo, and ECT is
more effective than pharmacotherapies (61, 165).
Pharmacotherapies are a common treatment for depression. In 2010,
757 000 patients were treated with antidepressants in Sweden (149). Selective serotonin reuptake inhibitors are most commonly used because they
have relatively modest side effects, although adverse sexual effects are
common (118). Other classes of antidepressant medications include serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, and
monoamineoxidase inhibitors.
The recommended treatments for bipolar disorder also include lithium,
lamotrigine, valproate, and antipsychotic agents (40). For some patients,
lithium treatment can augment the effects of antidepressants, and some
studies suggest that lithium has prophylactic effects on unipolar depression
(6, 7). Some second-generation antipsychotics are effective for acute treatments of major depressive disorder (64), but few studies suggest that they
effectively prevent relapse of major depressive disorder (16).
23
Electroconvulsive therapy
History of ECT
The early history of ECT is well described by Shorter (141). Briefly, doctors have known for hundreds of years that acute manic states can be terminated by epileptic seizures. In the 16th century, Paracelsus used camphor
to induce seizures when treating mental disorders. However, the modern
era of convulsive therapies can be traced to the 1930s and to the Hungarian psychiatrist Meduna. Meduna studied histological preparations from
diseased patients and found that patients with epilepsy have a larger number of glial cells than patients with schizophrenia. Based on this observation, Meduna decided to treat schizophrenia with induced seizures. The
first patient he treated was suffering from catatonia and had been ill for
four years. Meduna used a series of camphor-induced seizures as a treatment, and the patient completely recovered. However, chemically induced
seizures were difficult to control and were uncomfortable for the patient in
the time interval before the seizure. Therefore, attention became focused on
the usage of electrically induced seizures.
Following successful attempts in animals, Cerletti and Bini administered
the first electroconvulsive treatment to a human in 1938. The patient was
found in a psychotic state in a railway station and was then treated in a
hospital without significant improvements. The doctors were unsure of the
stimulus intensity necessary to induce seizures in humans, and the first
electrical stimulus attempted was too low to induce a seizure. Nonetheless,
after experiencing the first electric current the patient uttered, not again,
its murderous. The second stimulus elicited a generalised seizure, and the
patient recovered after a series of 11 treatments.
By the 1940s, electrically induced seizures were standard and pharmacologically induced seizures had been abandoned. ECT had been introduced
to many parts of the world and was recognised as a valuable treatment for
schizophrenia. Interestingly, the most prominent effects were seen in patients with mood disorders. However, vertebra fractures were a feared
complication of ECT. In the 1940s, trials were conducted with curare in an
attempt to reduce the fracture risk, but the problem was not solved until
1951 when the Swedish psychiatrist Holmberg and anaesthesiologist Thesleff introduced succinylcholine-modified ECT (48). This modified form of
ECT used anaesthesia to help the patients tolerate the muscle-relaxant.
ECT was then converted from an office-based procedure to a hospitalbased procedure, which reduced the availability of the treatment.
24
In the 1960s, Ottosson performed a series of experimental studies of ECT

(102). From the 1970s onward, Ottosson, dElia, and others pioneered
research in many areas of ECT including the mode of action, electrode
placement (21), technical aspects, the importance of the seizure quality,
and cognitive effects (17, 20, 28, 98, 154, 163). To this day, treatments are
being technically refined with the goal of reducing the cognitive effects
while retaining efficacy (1, 56, 137).
Mode of action of ECT

Knowledge about the mode of action has increased, but ECT is still not
fully understood (30). In 1960, Ottosson demonstrated that generalised
seizures were essential for effective ECT. Sub-convulsive seizures had no or
weak antidepressant effects (102).
Several brain areas are thought to be important for the mode of action of
ECT. Cortical-subcortical networks participate in the initiation and propagation of generalised seizures and the activation of the brainstem (81).
Prefrontal and central areas of the brain are thought to be important in the
pathophysiology of depression (35), and are hypothesised to be key areas
to target for epileptic seizures. Animal experiments show that ECT can
stimulate cell replication in the hippocampus (46), and magnetic resonance
imaging studies in humans indicate similar effects (93). Moreover, functional magnetic resonance imaging studies show that ECT restores blood
flow to networks that are disturbed in depression (105).
There are several biochemical effects of ECT. Repeated seizure inductions
stimulate systems that are engaged during the tonic phases of the seizures
(107) and systems that counteract and terminate the seizures (13). Therefore, ECT regulates the activity of neurotransmitters such as monoamines
and the balance of gamma-aminobutyric acid (GABA) and glutamate (129,
171). Furthermore, ECT normalizes the neuroendocrine system, including
the hypothalamus-pituitary-adrenal axis, which is frequently disturbed in
severe depression (80). However, how these biological mechanisms interact
to decrease depressive symptoms remains unknown.
ECT administration
ECT is administered during a short anaesthesia. The treatment is safe and
painless, apart from the pain associated with receiving an intravenous infusion. There are no significant contraindications to ECT, but some conditions, such as severe circulatory or respiratory disease, increased intracranial pressure, metal implants in the head, and poor dental status, may be
25
associated with increased risks of complications. A treatment series usually

consists of 612 treatments over a 24 week period. A significant improvement in mental state is often observed after a few treatments, but in
some cases, as many as 20 treatments may be necessary (164).
There are currently three frequently used electrode placements in clinical
practice: unilateral, bilateral, and bifrontal. Unilateral electrode placements
are most common in Europe and Australia, but bilateral electrode placements predominate in most other parts of the world (66). The unilateral
dElia placement (19) is most commonly used in Sweden since unilateral
treatment is associated with a lower risk of amnesia and confusion (126).
The time to symptom reduction is longer with unilateral electrode placement than with bilateral electrode placement, and markedly higher electrical charges are necessary to induce therapeutically optimal seizures (56,
126). Bilateral electrode placement may be preferable when the severity of
the symptoms demands a fast response, and a fast response is prioritised
over the risk of amnesia. Bifrontal electrode placement is less common, but
is generally considered to be intermediate to unilateral and bilateral electrode placements (56).
The electrical pulse amplitude, width, frequency, and total stimulus time
can all be adjusted with currently used ECT devices. The manufacturers
provide tables with recommended initial doses based on the age and sex of
the patient. The electrical charge required to induce a seizure tends to be
larger in men than in women, and larger in older patients than in younger
patients. Other factors that influence the seizure threshold are concurrent
medication and anaesthesia. Hypocapnea is induced by hyperventilating
the patient during anaesthesia to decrease the seizure threshold. In clinical
work, the aim is to find the optimal stimulus intensity to balance the antidepressive effect and the risk of amnesia. In 1963, an ultra-brief pulse
width was introduced but this technique was abandoned because it produced less generalised seizures (18). However, a recent clinical trial of ultra-brief pulse width (0.30.5 ms) ECT reported an antidepressive effect
and a lower risk of amnesia than for standard brief pulse width (0.51.0
ms) ECT (128). However, it is possible that ultra-brief pulse width stimuli
are less effective than brief pulse stimuli (72).
The immediate treatment effect of ECT is an epileptic response. This response is monitored by observation of motor activity, electroencephalogram activity, cardiovascular response, and the postictal state. The aim in
the clinic is to balance the risks of suboptimal treatment effects and the risk
26
of amnesia by modifying the treatment technique according to the response.
Indications for ECT

The American Psychiatric Association (APA) guidelines (164) give the following indications for the use of ECT among patients with depression:
-
the need for a rapid and definitive response (e.g., because of the severity of psychiatric or medical condition or deterioration of the patients
status)
a lack of response to, or intolerance of, antidepressant medications in
the current episode
a history of poor medication response or good ECT response in one or
more previous episodes
when the risks of other treatments outweigh the risks of ECT
patients preference
The APA guidelines say that ECT may be safer than alternative treatments
for the infirm elderly and during pregnancy. The decision to use ECT depends on several factors, including the severity and chronicity of depression, the likelihood that alternative treatments would be effective, the patient's preference and capacity to consent, and weighing the risks relative
to the benefits. The APA guidelines (164) state that severe major depressions with psychotic features, manic delirium, or catatonia are conditions
where there is a clear consensus that favours early ECT. Mania is an indication for ECT, but the treatment is generally reserved for patients with
very severe symptoms or patients who do not remit with pharmacotherapies. Neuroleptic malignant syndrome and Parkinsons disease can also be
indications for ECT.
The UK National Institute for Health and Clinical Excellence (NICE)
guidelines (90, 91) have similar recommendations for ECT as the APA
guidelines for patients with severe or treatment resistant depression, catatonia, or prolonged or severe mania. The NICE guidelines do not recommend ECT for schizophrenia, which is different than the APA guidelines.
The APA guidelines say that ECT is rarely used as a first-line treatment for
schizophrenia, but can be considered after unsuccessful treatments with
antipsychotic medications, and may also be considered when treating patients with schizoaffective or schizophreniform disorders. The latest Cochrane review offer some support for the combined use of antipsychotics and
27
ECT in schizophrenia (161), but there are few randomised controlled trials
that use this combination of treatments.
Swedish recommendations and Swedish clinical practice conform relatively
well to these international guidelines (3, 94, 103, 148).
ECT worldwide
It is estimated that one million patients worldwide receive ECT each year
(111). However, the rates of use vary considerably across countries. In the
US and Western Europe, about five patients per 10 000 people are treated
with ECT annually. However, the treatment is less common in countries in
Southern and Eastern Europe. The annual rate is estimated to be only 0.11
patients per 10 000 people in Poland (66). Over the past two decades,
there has probably been a slight increase in the number of ECT treatments
administered in Sweden, and the most recent estimate is that approximately 30004000 Swedish patients receive ECT each year, with a total of
30 00040 000 treatments administered annually (3). In Western countries,
ECT is primarily used for treatment of depression. However, in Asia, ECT
is more commonly administered for treatment of schizophrenia than depression. In some developing countries, ECT still occurs without anaesthesia (66).
Effectiveness of ECT
Randomised studies show that ECT is significantly more effective than
sham-ECT in reducing depression symptoms (115). In clinical trials, the
efficacy of ECT in severe depression is high, with remission rates of 6070 %
or more (106, 165). By contrast, remission rates are approximately 30 %
in trials of pharmacotherapies or psychotherapies (133). In severe depression, active medications are markedly more effective than placebo and ECT
is even more effective than pharmacotherapies (165). In fact, no randomised trial has ever reported that pharmacotherapies are more effective than
ECT for severe depression (158). ECT has not been extensively compared
to medication in randomised trials of moderate depression (133).
Despite these convincing results, there may be a gap between the results
achieved by ECT in clinical trials and the effectiveness of ECT in clinical
practice. In a study by Prudic et al. that was conducted outside of the
framework of a clinical trial, the remission rate was only 3047 %, depending on the criteria for remission (110). Suboptimal treatments or to
few treatments could contribute to the discrepancy. Another possibility is
that lower remission rates in clinical practice may be due to patient selec-
28
tion since patients with co-morbidities are often excluded from clinical
trials but are included in clinical practice. If these patients are less likely to
benefit from ECT, then this may contribute to the discrepancy. Regardless,
the fact that a significant proportion of patients do not respond to ECT in
clinical practice is a severe clinical problem. By the time ECT is considered,
drug therapies have likely been tried alone or in parallel with ECT, and the
prognosis for these non-responders is already poor. The ability to identify
individuals that are likely to respond to ECT would therefore be of great
benefit to clinical practices.
Predictors of the short-term effectiveness of ECT

The presence of psychotic symptoms (29, 106), lower degrees of prior
treatment resistance (23, 26, 109), and shorter symptom durations (26, 62)
are relatively well established predictors of response to ECT (73). In addition, the Collaboration for research in ECT (CORE) group reported higher
ages to be associated with favourable outcomes (96). Patients with co morbid personality disorders have lower responder rates to ECT (130) and
other treatments for depression (89) than patients without personality disorders. In a study from Finland, younger patients suffering from moderate
depression and with co-morbidity had a lower response rate than severely
depressed older patients without co-morbidity (45). However, there are
variations in the results and the importance of several factors is debated. In
particular, the importance of psychotic depression (23, 146) and greater
initial severity (63) have been questioned. Thus, more data is needed to
determine the importance of various predictors for the response to ECT.
Cognitive effects of ECT
The cognitive effects of ECT, and in particular the effects on memory, are
regarded as one of the most important limitations of the treatment (91, 94,
164).
During a series of ECT sessions, the ability to concentrate usually normalises rapidly but memory encoding may be temporally impaired. The ability
to store memories tends to normalise within a few weeks (137). However,
the effect of a series of ECT sessions on long-term memory is still debated
(11). Memory involves a number of complex cognitive functions and is
influenced by many factors including emotional state, disease, and therapy.
Memory dysfunctions can be divided into objective dysfunctions in specific
domains and subjective dysfunctions. Objective and subjective dysfunctions
are not well correlated (117).
29
At least three separate processes are involved in memory: encoding, consolidation and storage, and retrieval. Encoding requires attention and concentration, functions that are commonly affected by mental disorders. Consolidation and storage are thought to involve temporal regions of the brain
and the hippocampus, and retrieval involves prefrontal cortical areas (24,
95).
Memory dysfunctions related to ECT can be divided into anterograde amnesia, which involves impairments in episodic short-term memories during
and after treatment, and retrograde amnesia, which involves impairments
in episodic memories from before the treatment.
Anterograde amnesia
Anterograde amnesia is common in patients treated with ECT due to temporary dysfunctions in encoding (17). The frequency and severity of anterograde amnesia is influenced by electrode placement (bilateral treatment
causes more dysfunction than unilateral), treatment spacing (one treatment
per week causes less dysfunction than three treatments per week), and
stimulus dosing (164). In addition to a reduced ability to encode and store
new memories, ECT can result in a temporarily reduced ability to retrieve
old memories. The degree of impairment can vary over the treatment period. Some patients have longstanding memory gaps throughout the treatment period, and both the disease and the treatment could contribute to
this phenomenon.
Some cognitive functions, including attention and concentration, tend to
improve during treatment in parallel with reduction of disease symptoms.
A recent meta-analysis showed that objective memory functions were restored within two weeks of treatment (137). Although some studies indicate that subjective memory impairments can remain for longer periods of
time (34), most patients do not show any residual impairments by two to
six months after the completion of treatment (138). However, even if there
are no evident objective dysfunctions, temporary anterograde amnesia
during the treatment period could influence confidence in memory, and
decreased confidence in memory functions may affect the subjective perception of memory (151).
Retrograde amnesia
Neuropsychologists evaluate retrograde amnesia by testing functions important for retrieval of long-term memory (67). A recent meta-analysis
30
concluded that there were no long-lasting impairments in these functions

after ECT at the group level (137). However, some patients reported retrograde amnesia after ECT. Memories from time points around the treatment
periods are most vulnerable. However, a causal link is difficult to demonstrate from these case reports.
In one observational study, there was a dose-response relation between the
number of treatments with bilateral electrode placement and memory performance as assessed with an autobiographical memory inventory short
form at six months after treatment (127). However, this questionnaire has
been criticised and is not validated (139). The answers given in the depressed state before ECT are recorded. All later deviations from the pretreatment answers are considered incorrect. Therefore, the patients cannot
improve their performance after ECT. If something is remembered incorrectly in a depressed and confused state, but is remembered differently and
clearly in a non-depressed state, then the score is zero points. This type of
construction risks that the association between the performance on the
questionnaire and the different treatment intensities is biased by the severity of the disease. Therefore, although this study is interesting and widely
cited, there is no firm evidence that retrograde amnesia occurs after ECT.
In fact, the results from a controlled trial indicated that long-term memory
functions are similar in patients treated with ECT and patients treated
pharmacologically. The authors of this trial concluded that potential memory problems are not a reason to refrain from ECT (145). Nonetheless, in
clinical practice patients are often afraid of long-term memory impairments
caused by ECT, and further research is needed to clarify the cognitive effects of both depression and ECT.
There are additional factors that are important to consider when impairments in memory functions are suspected in patients who have been treated
with ECT. For example, residual depression or anxiety symptoms, other
mental disorders including early stages of neurodegenerative disorders, and
benzodiazepine treatments can all affect attention and concentration, and
can thus potentially impact memory functions (112).
Common side effects and complications of ECT

Adverse reactions to ECT are usually mild and treatment is well tolerated.
Headaches and muscle pains are frequent in ECT treated patients, but are
usually mild and subside with paracetamol. Tooth fractures are infrequent
but can occur despite standard dental protection. There are descriptions of
patients who have received thousands of ECT sessions without harm (69).
31
However, the safety of ECT for patients who are being treated with lithium
has been questioned (131).
Serious complications related to ECT

The most serious complications of ECT are caused by anaesthesia and the
fast increase in pulse and blood pressure that are induced by the seizure.
The risks are increased if the patient had a recent myocardial infarction or
stroke, or has vascular malformations and processes that increase intracranial pressure. Severe osteoporosis and poor dental status are other conditions that increase the risks associated with ECT. The mortality from ECT
is mostly connected to the anaesthesia and is estimated at one to two
deaths per 100 000 treatments (169).
Stigma associated with ECT
Stigma is a common experience for people with psychiatric diseases. This
stigma contributes to the reluctance of societies to allocate resources to
treatment, to hesitation of patients to seek care, and to poor compliance
with treatment. Several factors make ECT especially prone to stigma. ECT
was introduced at the same time as insulin therapy and lobotomy, two
therapies that are now considered obsolete. ECT is also associated with
severe psychiatric conditions and restraints. The view of ECT in the general
population has been heavily influenced by the exaggerated depictions of
ECT in movies as a brutal and suppressing treatment (77). In addition,
fears of seizures, electricity, and memory effects are widespread.
Ethics of ECT
In biomedicine there are four ethical principles that should be balanced:
beneficence (doing good), non-maleficence (not doing harm), autonomy,
and justice (8). In ECT the principles of beneficence and showing respect
for the patients autonomy can collide. About 15 % of patients who receive
ECT are involuntarily hospitalised patients (3). In my clinical experience,
many of these patients would prefer not to have ECT when ECT is initiated. However, when the symptoms abate, these patients often acknowledge the necessity of the treatment. It has been argued that involuntary
ECT should be reserved for patients with psychotic or suicidal symptoms
(101). It could be argued that a reasonable balance between beneficence
and respect for autonomy can be achieved with involuntary ECT treatment
in cases where medication is not likely to be helpful, the prognosis with
ECT is good, and the suffering of the patient would be long and severe
without ECT. In cases of involuntary hospitalisation, it could be considered unjust to withhold the treatment that provides the highest probability
32
of helping the patient. My view is that respect for the patients autonomy
should incorporate the likely opinion of the patient once the treatment is
concluded. However, if the patient will receive only a few benefits and
there will be side effects, then ECT may not be worthwhile. Therefore, the
risk of a poor outcome must be accounted for in all involuntary patients.
Relapse after ECT

Nearly half of all patients who receive ECT relapse within six months after
the conclusion of treatment despite receiving pharmacotherapies (57, 84,
108, 124, 160). As a result of relapse, psychiatric re-hospitalisation is often
necessary (50). The relapse/recurrence of severe symptoms is also associated with high risk of suicide. A suicide rate of about 10 % within ten
years after pharmacotherapies or ECT was reported in one Danish study
(86).
In clinical practice, various combinations of pharmacological agents are
used to reduce the risk of relapse/recurrence, but there are few studies that
compare the outcomes achieved with the different treatment strategies.
One of the most common strategies is the use of antidepressant medications. However, ECT is often given to patients who have already received
antidepressant drugs without benefits. These patients tend to have reduced
benefits from antidepressants after ECT relative to patients who did not try
antidepressants prior to ECT (116). One randomised trial found that a
lithium/antidepressant combination is more effective than antidepressants
alone for the prevention of post-ECT relapses and recurrences (124). However, a recent larger study testing this strategy resulted in a disappointing
50 % relapse rate (108). Thus, more effective treatments are needed to
prevent relapse/recurrence.
Continuation ECT to prevent relapse after index ECT

Weekly to monthly ECT can be used to prevent relapse after index ECT
(57, 97). This is referred to as continuation ECT. Before the pharmacological era, continuation ECT was the only effective measure to reduce the
relapse rate. However, this practice became uncommon after the introduction of antidepressants. Since there is a high relapse risk after ECT, and
most patients receiving ECT have already tried antidepressants with limited
benefits, recently there has been a renaissance of continuation ECT. This
practice is supported by a randomised trial in which continuation ECT
alone resulted in relapse rates similar to an antidepressant-lithium combination (57).
33
Continuation ECT is used in most hospitals in Sweden, but there are considerable variations in the proportion of patients who receive the treatment
(3). Most (114), but not all (75), retrospective studies have found that
medication combined with continuation ECT is effective in preventing
relapse. These studies suggest a reduced need for hospital care if continuation ECT is provided (36, 123, 136, 157, 168). Navarro and associates
performed a randomised trial of continuation ECT and nortriptyline in 33
elderly patients with psychotic depression. Five of the 13 patients who
completed the study in the nortriptyline group had relapse/recurrence, relative to only one out of 11 patients who completed the study in the continuation ECT plus nortriptyline group (87). However, more data from
randomised trials are needed to establish the relative effectiveness of pharmacotherapies, continuation ECT, and the combination of both of these
modes of treatment.
Summary and scope for the empirical studies

In summary, ECT is the most effective treatment for severe depression.
However, not all depressed patients respond to ECT. Accurate information
about the outcomes with ECT is necessary to correctly inform and guide
patients in the decision between treatment alternatives. However, recent
studies into the outcomes of ECT in routine clinical practice have been
scarce. Therefore, it is unclear how the outcomes in routine clinical practice compare to the good results reported from clinical trials.
Moreover, it remains a challenge to sustain any improvements that are
achieved with ECT. Despite continuation pharmacotherapies to prevent
relapse/recurrence, approximately half of all patients relapse within one
year. Retrospective studies have indicated that continuation ECT combined
with pharmacotherapies may be effective to reduce the high relapse rates,
but there has been only one small randomised trial that has explored this
combination.
34
AIMS
The overarching aims of the thesis were to identify clinical characteristics
that predict the outcomes of depressed patients treated in clinical practice
by ECT, and to elucidate the effectiveness of continuation ECT at preventing relapses and recurrences. The specific aims of the separate studies were:
I.
to investigate the responder rate of ECT, in clinical routine

work and to define clinical characteristics predictive of response to
ECT
II.
to define predictors of time to relapse after ECT for major depressive disorder, single or recurrent
III.
to test the hypothesis that relapse prevention with continuation ECT plus pharmacotherapy is more effective than pharmacotherapy alone after a course of ECT for depression and to compare
the safety of the treatments
IV.
to describe the need for inpatient care before, during and after
continuation ECT combined with pharmacotherapy
V.
to investigate the rate of regained occupational functioning after ECT and to define predictors related to time to regained occupational functioning in patients treated with ECT for major depressive disorders
35
36
936
Unipolar depression,
bipolar depression
and schizoaffective
disorder, depressed
type
Clinical Global
ImpressionImprovement score
available
Number of patients
Diagnoses
Clinical Global
ImpressionImprovement scale
Logistic regression
Outcome measure
Main statistical
method
Treatment response
Primary outcome
Additional inclusion
criteria
Cohort study based

on data from the
quality register for
ECT
Study design
Study I
Cox regression,
Kaplan-Meier
Hospitalisation or
suicide
Hospitalisation
Personal identification
number
486
Unipolar depression
Cohort study based

on data from the
ECT
Study II
MADRS score,
hospitalisation or
suicide
Kaplan-Meier, Log
rank ,Cox regression
MADRS 15 and
Clinical Global
Impression Improvement at least
much improved
Relapse
56
Unipolar and
bipolar depression
Multicentre
randomised trial
Study III
Kaplan-Meier
Amount of inpatient
care required
Inpatient days,
hospitalisation
27
Unipolar depression,
bipolar depression
and schizoaffective
disorder, depressed
type
Treatment with
continuation ECT
initiated
Retrospective chart
review
Study IV
Table 1. Overview of the studies contained in this thesis
Cox-regression,
Kaplan-Meier
Restored occupational functioning

Termination of sick
leave
Personal identification
number; Social
insurance coverage
during ECT
Cohort study based

on data from the
ECT and other
registers
394
Unipolar depression
Study V
METHODS
37
Table 2. Patient characteristics in each study
Study I
Study II
Study III
Study IV
Study V
n=936
n=486
n=56
n=27
n=394
Sex
Women
57 %
57 %
50 %
78 %
57 %
Age, years
Mean SD
54 18
55 18
57 15
48 19
45 11
Diagnoses
Major depression,
16 %
22 %
18 %
3%
21 %
60 %
78 %
64 %
66 %
79 %
19 %
0%
18 %
19 %
0%
5%
0%
0%
11 %
0%
Mild/moderate
32 %
36 %
23 %
0%
33 %
Severe, non-psychotic
44 %
44 %
39 %
N/A
48 %
Severe, psychotic
25 %
20 %
38 %
N/A
19 %
Involuntary care
15 %
13 %
13 %
N/A
15 %
Voluntary care
85 %
87 %
87 %
N/A
85 %
Outpatient care
19 %
25 %
23 %
4%
13 %
Inpatient care
81 %
75 %
77 %
96 %
87 %
Co-morbid
With diagnosed co-
27 %
30 %
38 %
7%
31 %
axis I diag-
morbid anxiety
nosis
With co-morbid sub-
11 %
10 %
0%
7%
13 %
8%
8%
9%
33 %
10 %
single episode
Major depression,
recurrent
Bipolar disorder,
depressive episode
Schizoaffective disorder,
depressive episode
Severity
Type of care
stance dependence
Co-morbid
With diagnosed co-
axis II diag-
morbid personality
nosis
disorder
38
Table 3. ECT-techniques (mean, standard deviation in parenthesis)
Study I
Study II
Study III
Study IV
Study V
Unilateral
Unilateral
Unilateral
Bifrontal
Unilateral
(82 %)
(88 %)
(100 %)
(100 %)
(83 %)
Index-ECT sessions
8.0 (3.2)
7.9 (3.0)
8.8 (2.1)
N/A
8.1 (3.2)
Pulse-width, ms
0.49 (0.14)
0.46 (0.10)
0.36
0.5
0.47 (0.12)
Frequency, Hz
73 (23)
75 (25)
74 (20)
70
70 (21)
Duration, s
7.4 (0.83)
7.5 (0.9)
6.40 (1.21)
N/A
7.4 (0.80)
Current, mA
840 (53)
833 (50)
813 (35)
900
840 (48)
Charge, mC
451 (186)
429 (177)
292 (166)
N/A
405 (150)
EEG seizure duration, s
33 (14)
34 (15)
39 (14)
N/A
35 (26)
Electrode placement
Table 4. Pharmacotherapies assessed at the conclusion of index ECT
Study I
Study II
Study III
Study IV
Study V
Antidepressants
87 %
91 %
98 %
79 %
92 %
Antipsychotics
39 %
29 %
30 %
61 %
37 %
Benzodiazepines
24 %
21 %
0%
0%
30 %
Lithium
16 %
10 %
56 %
32 %
10 %
39
Figure 1: Overlap of the participating patients in the different studies in this thesis
I
IV
II
III
Figure 1 shows that all patients in study II, III and IV participated in study I. Many
of the patients in study III and V also participated in study II. Study IV was based
on a separate cohort of patients.
40
Methods used in the separate studies

An overview of the methods used in the separate studies is presented in
table 1.
Patients included in the separate studies
An overview of the patients included in the separate studies is presented in
table 2 and figure 1.
Quality register for ECT
In Sweden, ECT is provided by the psychiatric hospital responsible for the
treatment of all patients within a defined geographical area. At the beginning of 2008, a quality register for ECT was initiated as part of a regional
collaboration involving rebro County Council, Uppsala University hospital and the Psychiatric Department in Ster. Lwenstrmska hospital
joined the register in 2009, and Danderyd hospital joined in 2010. Patients
are informed about the register and can choose not to participate, but written informed consent is not necessary for participation. Very few patients
abstain from participation. The aim of the quality register for ECT is to
collate data regarding patients treated with ECT to be used for research
and quality assurance. All data are recorded on paper forms by physicians
and nurses that are involved in the delivery of ECT, and the forms are then
sent to rebro and registered in a database. The diagnoses recorded in the
quality register for ECT conform to the International Classification of Diseases 10th version (147) and are transferred to the register from the hospital
charts. A registered nurse pays monitoring visits to participating hospitals
to ensure the completeness and high quality of the data.
Studies I, II, and V of this thesis are based on data from the quality register
for ECT. Data collected during the first four years of the register were
used. Eight hospitals participated in the register during this time period.
The data included in the quality register for ECT were personal registration
numbers, diagnoses, numbers of ECT sessions, ECT treatment parameters,
involuntary/voluntary statuses, outpatient/inpatient statuses, Clinical
Global Impression-Improvement CGI-I (41) scores, Montgomery sberg
Depression Rating Scale (MADRS) (85) scores, Montgomery sberg Depression Rating Scale-Self-assessment (MADRS-S) (156) scores, and the
treatments used to prevent relapses (pharmacotherapies/continuation
ECT). The psychiatrist in charge of each patient determined the diagnosis,
and experienced nurses assessed the CGI-I.
41
Rating scales
The Clinical Global ImpressionImprovement (CGI-I) scale (41) score is a
global scale for clinical assessment. It includes scores of: 1 (very much improved); 2 (much improved); 3 (minimally improved); 4 (not improved); 5
(minimally worse); 6 (much worse); and 7 (very much worse). CGI-I was
used in studies I, II, III, and V.
The Clinical Global ImpressionSeverity (CGI-S) scale (41) score is a global
scale for clinical assessment. It includes scores of: 1 (normal, not ill at all);
2 (borderline mentally ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill);
6 (severely ill); and 7 (among the most extremely ill). CGI-S was used in
study I.
The Montgomery sberg Depression Rating Scale (MADRS) is a 10-item
interview-based scale designed to assess changes during treatment of major
depression. The scores range from 0 (without symptoms of depression) to
60 (maximal symptoms) (85). The MADRS-S is a nine-item variant of the
MADRS scale that is designed for self-assessment of depression (156). The
scores range from 0 (without symptoms of depression) to 54 (maximal
symptoms). MADRS and MADRS-S were used in studies I and III.
Cognitive status was evaluated using the mini-mental state examination
(MMSE) and the cognitive subscale of the Alzheimer's Disease Assessment
Scale (ADAS-cog) (83). The MMSE scores range from 0 (maximal deficit)
to 30 (no deficit) (31). The ADAS was developed to assess cognitive status
among patients with Alzheimers disease. The cognitive subscale scores
range from 0 (no mistake) to 85 (no correct task). MMSE and ADAS-cog
were used in study III.
Side effects were evaluated using the Utvalg for Kliniske Undersogelser
(UKU) scale that was designed by the Subcommittee of the Scandinavian
Society of Psychopharmacology to detect side effects in clinical trials of
psychopharmacology (68). More specifically, the memory item in UKU was
used in study III to assess subjective memory disturbances. It was administered at 2, 6, and 12 months after inclusion in the study and at relapse. The
scores range from 0 (no problem) to 3 (severe memory loss).
The mini-international neuropsychiatric interview MINI-PLUS 5.0 (140)
was administered in study III by investigators at each hospital prior to
randomisation as a diagnostic aid. In addition, the investigators had access
to the patients charts and clinical history.
42
Statistical analysis
The statistical methods used in the different studies are described in table
1. Frequency distributions across groups of patients were tested using chisquare tests (studies I, II, III, and V). Differences between means across
groups of patients were tested by Student's t-test (studies I, II, III, and V).
The factors evaluated for the analyses in studies I, II, and V were age, sex,
diagnosis, co-morbidity, outpatient/inpatient status, and involuntary/voluntary status. In addition, clinical improvements from ECT and
pharmacotherapies at the end of ECT were evaluated in studies II and V. In
study V, the duration of antidepressant treatment before ECT and the duration of sick leave prior to ECT were also evaluated. Multivariate logistic
regressions were used to calculate odds-ratios of responses relative to factors with statistical trends (p<0.10) of association to responses as determined by chi-square tests (study I). Kaplan-Meier survival curves were used
to calculate the cumulative probability of patients without relapses (study
III), patients without psychiatric hospitalisations (studies II and IV), and
patients who regain occupational functioning (study V). All randomised
patients were included in the intention to treat analysis (study III). The
relapse rates in the treatment groups were compared among patients with
and without resistance to pharmacotherapies, with and without lithium
treatment, and with and without remaining depressive symptoms (MADRS
score of 1015) after index ECT. Cox proportional hazards models were
used to generate 95 % confidence intervals of hazard ratios and to test if
there were statistically significant differences in hospitalisations (study II),
relapses (study III), and occupational functioning (study V). Repeated
measures analyses of variance were used to compare measures of cognitive
functions (MMSE, ADAS-cog) across time points (baseline, 2 months, 6
months, and 12 months) and treatment groups (pharmacotherapy alone,
continuation ECT plus pharmacotherapy) (study III).
All statistical tests performed were two-sided and alpha was set to 0.05. All
analyses were performed using SPSS version 15.0 (SPSS Inc., Chicago, Ill).
Data are reported as mean (standard deviation) unless otherwise stated.
ECT
Mainly unilateral electrode placements were used in studies I, II, III and V.
In study IV, bifrontal electrode placements were used. Details about the
dosages that were used are presented in table 3.
43
Pharmacotherapies
The pharmacotherapies that were used are presented in table 4. Nearly all
patients were exposed to at least one psychotropic drug. Antidepressants
were the most common, but nearly one third of all patients also received
antipsychotics and benzodiazepines. Lithium was used in only about 10 %
of the patients. However, in study III, lithium was used by half of the patients and benzodiazepines were not used.
Study I
Design
Study I was designed as a naturalistic cohort study based on data from the
quality register for ECT (table 1).
Patients
Nine hundred and ninety patients who were treated with ECT for a major
depressive episode of unipolar depression, bipolar depression, or schizoaffective disorder, depressed type were identified. Information about the
clinical outcome was available for 936 patients, and these patients formed
the study sample (table 2).
Outcome measure
Response to treatment was the primary outcome, and it was evaluated
using the CGI-I score. Patients who were rated as very much improved
or much improved were classed as responders to ECT.
Study II
Design
The design was a naturalistic cohort study based on data from the quality
register for ECT with additional follow-up data collected from the national
Causes of Death Register (table 1).
Patients
All 486 patients with a diagnosis of major depressive disorder (either single
episode or recurrent) were included (table 2).
Follow-up
Follow-up data were reported to the register during summer/autumn,
2010. The mean follow-up time was 582 (183) days after the end of indexECT.
44
Outcome measure
Time to psychiatric hospitalisation and death due to suicide were used as
indicators of relapse/recurrence. The starting point for these measures was
the last day of the first index ECT series recorded in the register.
Study III
Design
The study was a multicentre, non-blinded randomised trial with two parallel groups: pharmacotherapy alone and pharmacotherapy with continuation ECT. The allocation ratio was 1:1 (table 1).
Patients
Fifty-six patients were randomised in the study (table 2). Inclusion criteria
were a major depressive episode (either a single episode, recurrent episodes,
or an episode of bipolar depression) verified by MINI-PLUS, a score of no
more than 15 points on the MADRS scale at the end of index ECT, a rating of at least much improved on the CGI-I scale at the end of index
ECT, and informed consent. Patients were excluded if they had substance
dependence or a history of substance abuse within the last year. Patients
were enrolled within three weeks of the final index ECT session. Two hundred patients who completed an index ECT series at one of the four participating hospitals were considered for enrolment (figure 2).
Randomisation
A separate randomisation sequence was generated for each hospital. Small
blocks of different sizes were used. A statistician provided envelopes containing information about the randomised treatments.
45
Assessed for eligibility n=200
Did not meet inclusion criteria n=11

Exclusion criteria n=8
Refused to participate n=116
Other reason n=9
Randomised n=56
Allocated to ECT + pharmacotherapy n=28

Received ECT + pharmacotherapy n=26
Received pharmacotherapy alone n=2
Lost to follow-up n=0

Discontinued ECT n=7
Analysed n=28
Excluded = 0
Allocated to pharmacotherapy alone n=28

Received pharmacotherapy alone=28
Lost to follow-up n=0
Analysed n=28
Excluded=0
Figure 2. Participant flow (study III)
Interventions
All patients received individualised medication. Venlafaxine was the first
choice and lithium augmentation was offered to all patients. The serum
concentration of lithium was 0.56 (0.21) mmol/L in the pharmacotherapy
group and 0.60 (0.15) mmol/L in the ECT plus pharmacotherapy group. In
addition, antipsychotic medications were allowed. Anticonvulsant drugs
were not used in either group due to the hypothetical risk of interaction
with ECT. The pharmacotherapies at randomisation consisted of antidepressants (98 %), lithium (56 %), and antipsychotics (30 %) (table 4). If
the patient experienced a relapse, then the psychiatrist in charge was free to
recommend any treatment judged to be beneficial for the patient. This
included ECT for patients who were randomised to pharmacotherapy only.
The patients randomised to continuation ECT plus pharmacotherapy were
offered weekly ECT for six weeks and then biweekly ECT for 46 weeks,
for a total of 29 sessions of ECT over one year. Unilateral ultra-brief pulse
ECT was used (table 3).
46
Follow-up
Patients were telephoned weekly for the first six weeks and then biweekly
to complete a MADRS-SA. If the rating was above 20 points, then the
patient was seen by the investigator within one week to determine if there
was a relapse. The patients were also seen and evaluated by an investigator
using rating scales (MADRS, MMSE, ADAS-cog, and UKU) at the time of
randomisation and at two, six, and twelve months post-randomisation.
Four patients in the pharmacotherapy arm and two patients in the ECT
plus pharmacotherapy arm declined to be interviewed by telephone for
completion of the MADRS-SA forms.
Sample size
A power analysis before the study anticipated a relapse rate of 55 % in the
pharmacotherapy group and 25 % in the combined ECT and pharmacotherapy group. Forty-five patients were considered to be necessary for each
group based on a two-sided log-rank test with alpha set at 0.05 and 80 %
power. However, the study was terminated when there were 28 patients in
each group due to slow recruitment.
Outcome measure
The primary outcome was relapse defined as a score higher than 20 on the
MADRS, or hospitalisation, or suicide, or suspected suicide. The secondary
outcome was safety and included cognitive functions as measured with
MMSE, ADAS-cog, and the memory item of the UKU.
Study IV
Design
The study design was a retrospective chart review (table 1).
Patients
The 27 patients included are described in table 2. The study sample comprised of all patients who had commenced continuation ECT at the rebro
University Hospital for treatment of a depressive episode in the years before the randomised trial was initiated.
Continuation ECT
Continuation ECT was defined as ECT administered once per week or less
and provided in a voluntary outpatient setting. Continuation ECT was
usually given once per week during the first four weeks after index-ECT,
and then once every two weeks for an additional four weeks, and then
47
once per month for four months. However, there were individual adaptations in the schedule with some patients having shortened continuation
ECT schedules and some patients having continuation ECT initiated at a
frequency of once every two weeks.
Pharmacotherapies
The pharmacotherapies are described in table 4. Only one patient chose
not to have pharmacotherapy during continuation ECT.
Outcome measure
The uses of inpatient care during the three years before index ECT, during
the continuation ECT, and during the two years after continuation ECT
were quantified by a hospital day quotient (HDQ). The formula is described in the definitions section.
The hospitalisation rates were also calculated.
Study V
Design
The design was a nested cohort study based on data from the quality register for ECT and the Swedish Social Insurance Agency Registry (MIDAS).
Additional information was obtained from the Prescribed Drug Register
and the Causes of Death Register. The National Board of Health and Welfare in Sweden holds both of these registers (table 1).
Patients
Three hundred and ninety-four patients were included (table 2). Of these
patients, 266 had a non-permanent sick leave certificate and 128 were
granted disability pension. All patients with a diagnosis of major depressive
disorder (either single episode or recurrent) who were treated with ECT in
one of the seven hospitals that participated in the quality register for ECT
were considered for this study. Patients were included in this study if they
had insurance coverage (full day) from the Swedish Social Insurance Agency during ECT (sick leave or disability pension) and a Swedish personal
identification number. Patients were excluded if they had bipolar disorder
or if they were more than 62 years old at the time of ECT.
Outcome measure
The mean follow-up time was 772 (339) days after the last day of the first
index ECT series. Data about all compensations due to sick leave and dis-
48
ability pension that were longer than 14 days from 1995 to September,
2011, were obtained from the Swedish Social Insurance Agency based on
the personal identity numbers of the patients. The primary outcome measure was time to regain occupational functioning. This measure was identified by the termination of full day sick leave compensation.
The National Board for Health and Welfare administers the Causes of
Death Register and the Prescribed Drug Register, which are both based on
the personal identity number. Information about all causes of deaths up to
December, 2010, and medications provided for outpatient care from 2005
to August, 2011, were obtained. Medications collected within three
months of ECT were analysed and the durations of antidepressant medications before ECT were estimated.
Ethical considerations
Participation in a controlled study involves a certain degree of intrusion
into the autonomy of patients since the treatments are selected by chance
rather than by choice. All patients in study III provided informed consent
to participate and the families were informed. For the studies based on the
quality register of ECT (studies I, II, and V), the patients were informed
about the register and could choose not to participate. However, very few
patients declined registration.
When considering the ethical justification for these studies, we accounted
for the severity of the disease, the seriousness of the prognosis, and the
large variation in the proportion of patients treated with continuation ECT
between different hospitals. When studies III and IV were initiated, no
randomised studies about the effects of continuation ECT had been published. Knowledge about the outcomes of different treatments increases
through research. Due to the high risk for symptom relapse/recurrence in
depression, many of the participating patients may benefit from the results
of these studies during future episodes of depression. When all of the risks
and benefits were accounted for, our view was that the clinical and scientific benefits of these studies outweighed the risks for the participating
patients. All studies were conducted in compliance with the Helsinki declaration and were approved by the Regional Ethical Vetting Board.
49
Response
0.76; 1.45
0.39; 0.74
0.82; 2.23
0.20; 0.54
0.34; 0.89
0.59; 1.19
0.51; 1.37
0.27; 0.74
0.27; 0.56
1.12; 3.18
0.54; 1.12
0.74; 1.43
0.73; 1.80
Outcome
Females vs. males

Younger than 50 years vs. 50 years and older
First episode of depression vs. recurrent depression
Mild or moderate depression vs. severe depression with psychosis
Severe depression without psychosis vs. severe depression with psychosis
With diagnosed co-morbid anxiety disorder vs. without

With diagnosed co-morbid substance dependence vs. without
With diagnosed co-morbid personality disorder vs. without
Outpatient vs. inpatient ECT treatment
Involuntary vs. voluntary hospital admission during ECT
With benzodiazepine treatment vs. without
With antipsychotics vs. without
With lithium vs. without
Study I
0.83; 1.52
1.28; 2.82
0.88; 2.26
0.29; 0.64
0.66; 1.55
1.03; 1.99
1.10; 2.04
0.29; 0.92
0.86; 1.53
0.88; 1.60
0.88; 1.79
0.67; 1.52
0.76; 1.66
Hospitalisation
Study II
0.57; 1.03
0.42; 1.00
0.43; 1.32
0.69; 1.26
0.82; 1.72
0.36; 0.66
0.77; 1.33
0.74; 1.72
Regain of occupational
functioning
0.79; 1.34
0.56; 0.98
0.64; 1.19
0.57; 1.18
0.69; 1.37
Study V
Table 5. Ninety-five percent confidence intervals of the odds ratios of response, hospitalisation, and regain of occupational functioning
after ECT relative to clinical variables (studies I, II and V), significant correlations in bold.
RESULTS
51
Response to ECT (study I)

Table 5 shows the unadjusted 95 % confidence intervals of the odds-ratios
of response to ECT relative to clinical factors. A higher proportion of older
patients (>50 years of age) than younger patients responded to ECT (84.3 %
vs. 74.2 %, p<0.001). The response rate was similar in men and women.
Patients with severe, psychotic depression had a higher response rate (88.9
%) than patients with severe, non-psychotic depression (81.5 %) and patients with mild/moderate depression (72.8 %, p<0.001). However, the
response rates were similar among patients suffering from either a depressive episode of bipolar I or bipolar II disorder or a first or recurrent episode of major depressive disorder. There was a trend toward a lower response rate in patients with a depressive episode of schizoaffective disorder
(68.8 %, p=0.060, four degrees of freedom). The lower response rate in
patients with schizoaffective disorder, depressed type was statistically significant in a post hoc comparison to all other patients (p=0.04, one degree
of freedom). Patients with co-morbid anxiety or dependence disorders had
similar response rates to patients without such diagnoses. Patients with
personality disorders had a lower response rate than patients without personality disorders (66.2 % vs. 81.4 %, p=0.001). Table 6 shows the relative influences of clinical factors in a multivariate model.
52
Table 6. Multivariate logistic regression analyses of the influences of clinical factors on ECT responses (n=917)
Oddsratio
95 % confidence
interval
p-value
Outpatient
0.47
0.320.70
<0.001
Inpatient
Reference
Reference
Reference
Severity (mild/moderate)
0.37
0.220.63
<0.001
Severity (severe non-psychotic)
0.52
0.300.89
0.017
Severity (severe psychotic)
Reference
Reference
Reference
Age
1.01
1.001.02
0.006
Major depressive disorder, recurrent
Reference
Reference
Reference
Major depressive disorder, single

episode
1.16
0.691.94
0.583
Bipolar I, depressive episode
0.80
0.481.36
0.413
Bipolar II, depressive episode
0.68
0.371.24
0.205
Schizoaffective disorder, depressive episode
0.32
0.150.70
0.004
Hospitalisation after ECT (study II)

Out of a total of 486 patients, 185 (38.1 %) were hospitalised for psychiatric reasons during the follow-up period. The cumulative proportions of
the total sample of patients who were hospitalised were: 25 % within six
months, 34 % within one year, and 44 % within two years after the last
index ECT.
Fifteen patients died during the follow-up period. Nine patients died from
suicide and six from somatic diseases. The cumulative proportion of patients who died from suicide within one year after ECT was 2 %.
Table 5 shows 95 % confidence intervals of the unadjusted hazard ratios
of hospitalisation or suicide relative to clinical factors. The influences of
clinical factors on the hazard ratios of hospitalisation and suicide in a multivariate model are presented in table 7.
53
Table 7. Multivariate Cox-regression analyses of the influences of clinical factors

on the risk of psychiatric hospitalisation or suicide during the follow-up period
(n=479).
Hazard
95 % confidence
ratio
interval
pvalue
Outpatient
0.42
0.280.64
0.00
Substance dependence
1.88
1.262.80
0.00
Benzodiazepines
1.50
1.082.10
0.02
Antipsychotics
1.39
1.021.88
0.04
Lithium
0.58
0.321.02
0.06
54
Efficacy of continuation ECT (study III)
Figure 3. Kaplan-Meier function of the cumulative probability of remaining without relapse for patients treated with continuation ECT plus pharmacotherapy versus pharmacotherapy alone.
55
Relapse in the intention-to-treat sample

In the intention-to-treat cohort, the one-year relapse rates were 61 % in the
pharmacotherapy alone group and 32 % in the ECT plus pharmacotherapy
group (figure 3; p=0.036). The Cox proportional hazard ratio was 2.32 (95 %
confidence interval: 1.035.22). The two-month relapse rates were 29 % in
the pharmacotherapy alone group and 18 % in the ECT plus pharmacotherapy group. The six-month relapse rates were 54 % in the pharmacotherapy alone group and 29 % in the ECT plus pharmacotherapy group. In
the pharmacotherapy alone group, 36 % of patients required inpatient care
during the follow-up period, while only 20 % required inpatient care in the
pharmacotherapy plus ECT group. All hospitalised patients had relapses of
depression. There was one suspected suicide by intoxication during the
follow-up. The patient died from intoxication with mitragynin and Odesmetyltramadol. Although suicidal intent could not be proven, the event
was classified as a suspected suicide. The patient belonged to the pharmacotherapy alone group.
Relapse in post hoc subgroups
Among patients receiving lithium therapy, the one-year relapse rate was
56 % in the pharmacotherapy alone group (n=16) and 13 % in the ECT
plus pharmacotherapy group (n=15). Among patients not receiving lithium,
the relapse rate was 73 % in the pharmacotherapy alone group (n=12) and
64 % in the ECT plus pharmacotherapy group (n=13).
Among patients with a baseline MADRS scores 10 (indicating remission),
the relapse rate was 56 % in the pharmacotherapy alone group (n=24) and
24 % in the ECT plus pharmacotherapy group (n=25). Six out of seven
patients (86 %) relapsed among the patients with baseline MADRS scores
ranging from 11 to 15 (indicating remaining symptoms).
Among patients resistant to medication, the relapse rate was 85 % in the
pharmacotherapy alone group (n=13) and 31 % in the pharmacotherapy
plus ECT group (n=16). The relapse rate was 35 % in the pharmacotherapy alone group (n=15) and 33 % in the ECT plus pharmacotherapy group
(n=12) among the patients not resistant to medication.
Cognitive functions
The patients in the ECT plus pharmacotherapy group had better MMSE
and ADAS-cog scores at baseline than the patients in the pharmacotherapy
alone group (MMSE 28.4 (1.1) vs. 27.0 (2.7) and ADAS-cog 11.7 (13.7)
vs. 13.0 (15.2)). The scores of the ECT plus pharmacotherapies group were
56
better throughout the study. For patients who did not relapse, there were
no statistically significant differences in the development of the measures of
cognitive function (MMSE and ADAS-cog) or subjective memory (UKUmemory item score) between the ECT plus pharmacotherapy group and the
pharmacotherapy alone group.
Hospitalisation relative to continuation ECT (study IV)

The hospital day quotients (HDQ) were 28 in the three years preceding
ECT, 15 during continuation ECT, and 20 in the two years after continuation ECT. The hospitalisation rate was 50 % in the first year after index
ECT. Seven hospitalisations occurred (25 %) while the patients were receiving continuation ECT.
Time to regain occupational functioning after ECT (study V)

Out of the total sample of 394 patients, 245 (62 %) returned to work during the follow-up period. The cumulative proportions of the total sample of
patients returning to work were 31 % in the three months after ECT, 41 %
in the six months after ECT, 49 % within one year after ECT and 64 %
within two years after ECT.
Out of the 266 patients with non-permanent sick leave, the cumulative
proportions returning to work were 43 % in the three months after ECT,
59 % in the six months after ECT, 71 % within one year after ECT, and
88 % within two years after ECT.
Out of the 128 patients with disability pension, the cumulative proportions
returning to work were 3 % in the three months after ECT, 3 % in the six
months after ECT, 5 % within one year after ECT, and 19 % within two
years after ECT.
The influences of clinical factors on time to regain occupational functioning in a multivariate model are presented in table 8.
57
Table 8. Factors associated with regain of occupational functioning.

Hazard ratios and 95 % confidence interval values derived from multivariate Cox
proportional hazards-regression analyses among patients with non-permanent
sick leave that were treated for unipolar depression with ECT (n=252).
95 %
p-
ard
confi-
value
ratio
dence
Haz-
interval
Age below 50 years vs. 50 years and older
0.82
0.601.10
0.18
With anxiety disorder vs. without
0.99
0.701.39
0.94
With substance dependence vs. without
0.59
0.360.96
0.03
Pre-ECT sick leave 029 days vs. more than 365 days
2.89
1.684.97
<0.01
1.90
1.053.45
0.04
1.18
0.642.19
0.60
Mild/moderate depression vs. severe without psychosis
0.57
0.400.81
<0.01
Severe depression with psychosis vs. severe without psychosis
0.83
0.561.22
0.34
Benzodiazepine treatment vs. no benzodiazepine treatment
0.36
0.250.52
<0.01
CGI much improved vs. very much improved
0.97
0.711.39
0.97
CGI minimally improved vs. very much improved
0.42
0.250.69
<0.01
CGI not improved vs. very much improved
0.52
0.241.13
0.10
58
DISCUSSION
Overall, four out of five patients responded to ECT in clinical practice.
Patients with psychotic depression had the highest response rate. Approximately 90 % of these patients responded to ECT. The other patient groups
with high ECT response rates were: patients with severe depression, older
patients, and inpatients. These results were similar to published studies (96,
106). The patients groups with the lowest response rates were outpatients
and patients with personality disorders. However, two out of three patients
in these groups responded within three weeks of treatment. This response
rate is better as compared to a recent large randomised study of pharmacotherapy resistant depressed outpatients. In that study, 22 % of the patients
responded to pharmacotherapy alone and 44 % to pharmacotherapy plus
cognitive behavioural therapy after 6 months (100). Interestingly, study V
showed that a higher severity of depression was associated with reduced
time to regain occupational functioning. Psychotic depression tends not to
respond as well to medication (37, 54, 104). Therefore, the high response
rate to ECT emphasises the importance of ECT for treatment of psychotic
depression. Currently, only a minority of inpatients who are treated for
psychotic depression in Sweden receive ECT (3). The results of the studies
in this thesis suggest that there should be wider use of ECT in this patient
group.
Relapses/recurrences were very common. One-third of the patients treated
with ECT for unipolar depression required hospitalisation for a depressive
relapse and nearly 2 % committed suicide within one year of index ECT.
Patients with co-morbid substance abuse had an increased risk of hospitalisation, which suggests that these patients need to be identified and treated
differently.
A key finding of the studies in this thesis is that after patients were treated
with index ECT for depression, those who received continuation ECT and
lithium treatments had a lower rate of relapse/recurrence than the patients
who did not receive these treatments (study II, study III). Continuation
ECT also tended to reduce the need for inpatient treatment (study IV).
Nevertheless, the relapse rates were substantial for both treatment groups
in the randomised study. The estimated reduction in relapse rate with continuation ECT was 29 % (a relapse rate of 61 % for pharmacotherapy
alone vs. 32 % for pharmacotherapy and ECT). Thus, the number-to-treat
for one patient to benefit would be three to four. This level of risk reduc-
59
tion may be clinically relevant, especially if the disease is severe, the suicide
risk is high, or other treatments were unsuccessful. These results are consistent with other randomised studies that investigated the effects of antidepressant-lithium pharmacotherapies (108, 124), continuation ECT (57),
and continuation ECT combined with antidepressant medication (87).
Furthermore, the results support other studies that reported the efficacies
of lithium (124, 160) and continuation ECT (114) for depressed patients
who benefitted from index ECT. Importantly, study III in this thesis is the
first randomised study to investigate the effects of combined therapies including an antidepressant, lithium, and continuation ECT. The observation
that pharmacotherapy resistant patients received the largest benefit from
continuation ECT is very relevant for the clinic. Other studies found that if
patients did not respond to pharmacotherapies prior to ECT, then they had
a higher risk of relapse with pharmacotherapies after ECT (125). If continuation ECT can considerably reduce this relapse rate (study III suggests
that it can be reduced from 85 % to 31 %), then continuation ECT should
be recommended for this patient group. However, only a small minority of
patients receive lithium or continuation ECT treatment in current Swedish
clinical practice (3). Our research, in combination with earlier studies,
suggests that the wider use of these treatments would be beneficial. However, additional studies are necessary to confirm the effects of combined
continuation ECT and lithium treatments and to further define the indications for these treatments. These studies are currently being performed
(70).
Despite a high response rate to ECT, it often took months for patients to
regain occupational functioning. This finding is consistent with earlier
studies of pharmacotherapies and psychotherapies that found it takes long
time to regain occupational functioning after symptoms have decreased
(82). This has important implications for insurance practices. The current
decision issued by the National Board of Health and Welfare for physicians
and insurance personnel reads: In severe first episode depression, occupational functioning can be impaired up to six months. Depressive symptoms
can remain for an additional six months or longer. The individual variation
is large. Our research suggests that in two-fifths of patients with severe
depression who received ECT, occupational functioning was impaired for
longer than six months and that residual impairments for two years or
longer were not unusual. Furthermore, the time to regain occupational
functioning was not significantly different between patients with first or
recurrent depressive episodes. Our data confirm that there are large inter-
60
individual variations in the time taken to regain occupational functioning

after index ECT.
Patients who presented with depression with co-morbid personality disorder had a lower acute response rate to ECT (study I), a higher risk for rehospitalisation (study II), and a trend toward longer time to regain occupational functioning (study V) than patients without personality disorders.
This information is important for determining the prognosis of a patient.
Depressed patients with personality disorders also tend to respond poorly
to medication (89). Therefore, it is possible that ECT has the highest probability of providing responses when severe depressions are complicated by
personality disorders. The risks of non-response and side effects should
always be considered. However, the complication of co-morbid personality
disorders should not prevent physicians from using ECT to treat patients
suffering from severe depressions.
In study II, treatment strategies during the follow-up period were analysed
relative to the need for subsequent hospitalisations. It is difficult to draw
firm conclusions from naturalistic studies since the patients are not randomised and different factors that are related to selection might influence
the results. However, it is remarkable that the use of benzodiazepines and
antipsychotics during the follow-up period were associated with an increased risk of hospitalisation. Treatment with benzodiazepines, but not
antipsychotics, was also associated with an increased time to regain occupational functioning (study V). There are some indications that secondgeneration antipsychotics are effective for the acute treatment of mood
disorders (64, 88), but there are no published studies that support the longterm use of antipsychotics after ECT in patients with major depressive
disorder. The results of the studies in this thesis confirm the current guidelines that discourage long-term treatments with benzodiazepines. However,
in some Swedish hospitals, long-term benzodiazepine treatments are used
for patients who are treated with ECT (3). Therefore, smaller variations
between hospitals and closer compliance to guidelines are preferable.
Methodological considerations
Study I was an observational study based on prospectively collected data.
Ultimately, the patients hope to become free of symptoms and to regain
social functioning (to attain remission). In research settings, symptomatic
remission is usually evaluated with rating scales such as the Hamilton depression rating scale (HDRS) (42) or MADRS. In the quality register, the
MADRS scores were available for a minority of the patients. We consid-
61
ered the possibility that selection-bias might be introduced if the response

rates were influenced by the use of MADRS. For instance, if the use of
MADRS was associated with higher quality assessments and individualised
treatments, then patients rated with MADRS might have better outcomes
than other patients. Therefore, we did not use MADRS to assess the effects
of the treatments, and we did not evaluate remission. Instead, the main
outcome measure was response, which was based on the clinical global
impression-improvement (CGI-I) scores. This measure was chosen because
it was available for nearly all of the patients in the register. One disadvantage of CGI-I is that improvements among patients with mild symptoms
might be less apparent than improvements among very ill patients. Therefore, patients with milder symptoms may more often be rated as nonresponders than severely depressed patients. Similarly, for patients with
personality disorders, symptoms of personality disorders may be misinterpreted as remaining symptoms of depression. Further studies are necessary
to compare the CGI-I and MADRS ratings among different subgroups of
patients. Furthermore, it is important for future studies to evaluate the
proportions and characteristics of patients who achieve remission of symptoms with ECT treatments in routine clinical practices. The quality register
could contribute valuable information for these future studies.
Double-blind placebo controlled randomised clinical trials are the gold
standard for comparing the effects of different treatments. These types of
trials demand considerable resources. However, suboptimal treatments are
very unfavourable for patients and are also costly for the health care system. Therefore, it is important that treatments be evaluated by controlled
clinical trials.
Study III was a controlled clinical trial conducted without industry sponsors within the framework of routine clinical work. One limitation is that
the study enrolment was terminated early due to slow recruitment. Therefore, the estimations of the relative effectiveness of the treatments are wide.
The study is also limited by the absence of blinded assessors. Therefore, the
results could be biased if the doctors involved in the assessments had preconceived comprehensions about the treatment effects. This risk is only
partially balanced by the fact that patients participated in the assessments
of treatment effects, because the patients may also have been influenced by
similar perceptions. It was not feasible to employ qualified personnel to
assess outcome measures who were blinded to the treatments because of
the limited resources. In non-pharmaceutical interventions, such as surgery
and psychotherapies, it is generally challenging to blind the patients. It is
62
unknown whether patients would feel a difference between sham treatments and the actual ECT. Also, well-informed patients might not accept
sham treatments that still include the risks of anaesthesia. Therefore, even
though double-blinded studies provide a better level of evidence, there are
ethical limitations that can prevent these types of studies.
The patients in both treatment groups were contacted more often than
most other patients in routine clinical practice. Therefore, the intensified
access to care might also explain the lower rate of hospitalisation for patients in study III than for the patients in study II. Earlier detection of
symptom relapse/recurrence and adaptation is more likely when the patients are regularly assessed. Also, continuation ECT may have had a placebo effect that contributed to the reduced relapse rate of the patients randomised to that treatment group relative to the patients who received
pharmacotherapy alone.
Out of all patients eligible for inclusion in the randomised study, one-third
was included and two-thirds declined participation. The results that continuation ECT can prevent relapse are strong because the patients were
randomised. The patients included in the randomised trial were similar to
the patients in the population-based cohorts with regard to sex, age, diagnoses, severity of depression, and treatment setting (table 2). However,
some patients who received strong benefits from ECT were not included
because they preferred to obtain continuation ECT outside of the study.
There is a possibility that this biased the results toward a reduced efficacy
of continuation ECT. Other patients preferred pharmacotherapy alone and
were not included in the study because they would not accept additional
treatments with ECT. If those patients would have had received reduced
benefits from continuation ECT, then the results may be biased toward an
increased effect of continuation ECT. Therefore, although this study provides evidence that some patients benefit from continuation ECT, additional studies are necessary to estimate the relative effectiveness in subgroups of patients and to further define the indications.
It is appropriate to follow a cohort longitudinally when studying disease
prognosis. One advantage of cohort studies is that large data sets can be
collected with limited resources. The influence of recall bias is limited when
patients are followed and information is gathered prospectively. By contrast, recall bias can be a serious problem in case-control studies. Broader
categories of patients are more often included in cohort studies than in
randomised studies. Therefore, it is usually easier to generalise the results
63
of cohort studies to clinical settings. Moreover, it is possible to relate possible prognostic factors and exposures (such as treatments) to outcomes,
but it can be challenging to draw conclusions about causal relationships.
Selection bias can influence the association between treatment and outcome if certain patient groups with inherent differences in prognosis tend
to receive different treatments. Therefore, selection biases may explain why
continuation ECT was not associated with statistically significantly reduced risks of hospitalisation (study II) or time to regain occupational
functioning (study V). Although selection biases limit the conclusions that
can be drawn from observational studies, the associations found in observational studies can be used to form hypotheses, which can then be tested
in experimental studies.
The proportion of time spent hospitalised was compared before, during,
and after continuation ECT in study IV. The study was designed in this
manner because the patients who received continuation ECT could potentially be different than patients who received pharmacotherapies. For example, there may have been differences in response or adherence to pharmacotherapies. The patients act as their own controls in this design. The
results clearly showed that relapses/recurrences occurred with continuation
ECT and that there was a possible treatment effect on the need for hospitalisation. However, the index ECT series could also affect the disease.
Therefore, a control group that receives acute ECT and not continuation
ECT would also provide a relevant comparison. This type of group was
available for comparison in study II. Although the rate of hospitalisation
tended to be lower in the group that received continuation ECT than in the
group that only received medication, the difference was not statistically
significant. It is likely that the doctors anticipated higher relapse risks for
some patients because of differences in adherence or benefits from pharmacotherapies. If the doctors prescribed continuation ECT to patients with
higher relapse risks, then a differential relapse risk in the treatment groups
was introduced. This may have created a bias that increased the relative
relapse rate of patients who received continuation ECT relative to patients
who did not.
Scientific implications
This thesis presents the first randomised controlled trial of the combined
use of antidepressant-lithium pharmacotherapy and continuation ECT.
There was a statistically significant reduction in the relapse/recurrence risk
when patients were treated with combined antidepressant-lithium pharmacotherapy and continuation ECT. This result was expected and consistent
64
with clinical experience and earlier observational research. Larger studies

are required to confirm this result, and the results of study III provide an
assumption for the effect sizes in these future studies.
There have been only a few studies on the prognosis for occupational functioning in depression. The data in Study V in this thesis showed that data
on sick leave could be obtained and analysed among different groups of
patients who received different treatments. Therefore, it is likely that future
studies will use similar approaches. Furthermore, sick leave data can also
be used as a relatively hard end-point for future randomised studies in
addition to symptom rating scales.
Most of the clinical characteristics that influenced response rates were previously demonstrated (96, 106, 130). However, these results add to this
field of work and provide additional information about the strengths of the
associations because of the large sample size.
Clinical implications
Guidelines recommend that ECT be used to treat severe cases of depression. The results in this thesis are consistent with those recommendations
and strengthen the indication for ECT in the most severe cases of depression. The maintenance of remission is a great challenge when treating major depression. Many clinicians believe that continuation ECT is effective
in reducing relapse rates, but there is little evidence to support this hypothesis. The results in this thesis strengthen the indication for continuation ECT, especially for patients who did not receive benefits from pharmacotherapies alone.
In routine clinical practice, there is a high risk of relapse after treatment,
and a variety of different pharmacological agents are used to control the
symptoms of depression. Previous studies provided evidence for the efficacy of antidepressants and lithium in reducing the risk of relapse, but
lithium treatments are given as a post-ECT prophylaxis in only a small
fraction of the patients (3, 124). The results of the studies in this thesis
support the wider use of lithium. The use of benzodiazepines is sometimes
unavoidable because they reduce intolerable anxiety in severe psychiatric
disorders. The results of the studies in this thesis indicate that long-term
benzodiazepine treatment is associated with an increased risk of relapse/recurrence of depression and an increased time to regain occupational
functioning. Therefore, the benefits of benzodiazepines should be carefully
balanced against these risks.
65
Prescriptions of antipsychotics for unipolar depression have probably increased in the last decade. The scientific foundation underlying the adjunctive effects of antipsychotics combined with antidepressants in the longterm treatment of unipolar depression is weak. There are no published
studies that support prophylactic treatments with antipsychotics to reduce
relapse rates in patients treated for unipolar depression without psychotic
symptoms. Furthermore, there are no guidelines that recommend treating
such patients with antipsychotics. It is difficult to draw a firm conclusion
based on observational data because of the risk of selection bias. However,
the patients in our cohort who were treated with antipsychotics had a
higher relapse rate than patients who did not receive antipsychotics. All
antipsychotics have side effects and most are associated with weight gain.
Unless controlled trials are published that support the use of antipsychotics
in the long-term treatment of depression, the use of antipsychotics after
ECT in non-psychotic major depression should be restricted.
In recent years, there has been an ongoing debate about the contribution of
ECT to declining cognitive functions in patients with affective disorders.
The results of this thesis do not suggest that continuation ECT results in
long-term deficits in subjective memory or declines in cognitive functions.
This finding is consistent with published research (145), but more studies
are required.
In conclusion, the short-term response rates to ECT are relatively high for
all subgroups, and especially for older inpatients and patients with severe
depressions. Occupational functioning is often regained after ECT, but it
takes a considerably longer amount of time than symptom relief. However,
relapse/recurrence rates are high in the first few years after ECT. Continuation ECT and lithium treatment can be used to supplement antidepressants
in order to reduce this risk. More randomised controlled trials are necessary to define the indications for continuation ECT and lithium.
Further developments of other strategies that reduce the risks of relapse/recurrence of depression are required. To date, there have been no
clinical trials assessing combinations of ECT given in conjunction with
psychotherapy. Therefore, the effects of different combinations of ECT,
pharmacotherapy, and psychotherapy need to be assessed.
Also, no randomised trials that compare ECT to pharmacotherapies exclusively in patients suffering from moderate severity depression are published. Therefore, it is unknown if pharmacotherapies in combination with
66
ECT are more effective than pharmacotherapies in patients with moderate

depression. Randomised trials would be valuable to estimate the efficacy of
ECT plus pharmacotherapies relative to pharmacotherapies and pharmacotherapies combined with psychotherapies in moderately depressed patients
who do not remit within weeks of pharmacotherapy treatment. Moreover,
randomised studies are required to clarify whether there are any persistent
cognitive effects of ECT.
In other fields of medicine, there are biomarkers that can guide clinicians
to treatment alternatives. However, there are no biomarkers that are currently used in the routine clinical practice of treating mood disorders.
Hopefully there will be advances made that will allow combinations of
genes or other biomarkers to be useful for tailoring combinations of treatments to individual depressed patients.
67
68
SAMMANFATTNING P SVENSKA (SUMMARY IN

SWEDISH)
Elektrokonvulsiv terapi (ECT) r en behandling som anvnds vid svra
psykiska sjukdomar, framfr allt vid svr depression. Behandlingen har
anvnts i 80 r och r fortfarande den mest effektiva behandlingen vid svr
depression. Behandlingen r smrtfri och ges under narkos. Vid ECT framkallas ett epileptiskt krampanfall med hjlp av elektrisk strm. Behandlingen ges vanligen i serier om omkring tta behandlingar under cirka tre
veckors tid. Minnesstrningar i anslutning till behandlingen kan frekomma.
I kliniska frsk har ECT visat sig ge goda resultat vid behandling av svr
depression. Men det r oskert om resultaten r lika goda i klinisk praktik.
Dessutom r terinsjuknande vanligt, omkring hlften av patienterna terfr symptom inom ett r efter ECT, trots frebyggande lkemedelsbehandling. Det finns indikationer p att fortsttnings-ECT kombinerat med lkemedel kan skydda mot terfall men det behvs studier dr patienterna
slumpmssigt frdelas till olika behandlingsgrupper fr att underska om
sdan behandling r effektiv.
Syfte: Det vergripande syftet med avhandlingen var att identifiera kliniska
faktorer relaterade till utfallet av ECT fr depression och att belysa effektiviteten av fortsttnings-ECT fr att frebygga terinsjuknande.
Metod: Kvalitetsregistret anvndes i tre studier fr att beskriva utfall efter
ECT: vilka patientgrupper som tenderade att frbttras, vilka patientgrupper som snabbast kunde avsluta sjukskrivning och vilka patientgrupper
som tenderade att bli terinlagda p sjukhus. Andelen som terinsjuknade i
tv behandlingsgrupper som patienterna slumpmssigt frdelades till, fortsttnings-ECT i kombination med lkemedel eller endast lkemedel, jmfrdes i ett kliniskt frsk. I en journalstudie undersktes konsumtionen av
inneliggande vrd bland patienter som behandlats med fortsttnings-ECT.
Resultat: ttio procent av patienterna frbttrades omedelbart efter ECT.
Hgst andel frbttrade sgs bland patienter med psykotisk depression (89 %),
bland ldre patienter och bland inneliggande patienter. Den lgsta andelen
frbttrade sgs bland patienter med personlighetsstrning (66 %) och
bland polikliniska patienter (66 %).
69
Patienter som var sjukskrivna under ECT avslutade sjukskrivningen i 59 %,

71 % och 88 % av fallen efter 6, 12 och 24 mnader.
Andelen patienter som blev terinlagda p sjukhus var 25 %, 34 % och
44 % efter 6, 12 och 24 mnader. Andelen som terinsjuknade var hgre
bland dem som hade bensodiazepin-behandling och lgre bland litiumbehandlade.
Risken fr terinsjuknande var signifikant lgre bland patienter som fick
fortsttnings-ECT i kombination med lkemedel (32 %) jmfrt med dem
som endast fick lkemedel (61 %). Srskilt stor var effekten bland patienter som fre ECT hade prvat minst tv antidepressiva lkemedel med
otillrcklig effekt; bland dessa patienter terinsjuknade 85 % vid behandling med endast lkemedel jmfrt med 31 % vid behandling med fortsttnings-ECT i kombination med lkemedel. Behandlingen var ocks associerad med minskat behov av slutenvrd.
Slutsater: Andelen patienter som frbttras inom ett par dagar efter ECT r
relativt hg i alla studerade patientgrupper och srskilt bland inneliggande
patienter och patienter med svra former av depression. De flesta patienter
terfr arbetsfrmga efter ECT, men det tar lngre tid n symptomlindringen. Risken fr terinsjuknande r hg de frsta ren efter ECT. Fortsttnings-ECT och litium behandling kan adderas till antidepressiva fr att
minska risken fr terinsjuknande. Fler studier behvs fr att ytterliggare
definiera vilka patientgrupper som br f sdan tillggsbehandling.
70
ACKNOWLEDGEMENTS
I would like to thank:
The patients who participated in the studies and especially those who
agreed to be randomised between treatments.
Ingemar Engstrm, my main supervisor, for supporting me in every possible way, and for creating a good learning atmosphere and good working
conditions at the Psychiatric Research Centre. You are an inspiring example by your engagement in work, your integrity, and your wonderful personality. Moreover, you successfully communicate the need for integration
of evidence, experience and ethics. I hope we will be able to continue to
collaborate, and share more opera experiences together in the future.
Lars von Knorring, my supervisor; during my studies you have had many
duties, as a professor, advisor to the National Board of Health and Welfare, advisor to the Prison and Probation Service; you have prepared a new
act for psychiatric care and you are a member of numerous committees and
organisations. Despite all that, you have always found time for me. You
have always provided good advice, always participated in our meetings and
nearly always responded to my e-mails within a few hours (seven days a
week). Your experience is unique and you are an excellent diplomat. However, most importantly, I appreciate your patience. When I fail to listen to
your good advice, you simply sit back, smoke a pipe and continue to work
with a smile. I am very grateful; and I look forward to continue to work
with you on the quality register.
Ann-Charlotte Fridenberger, for all of your hard work during more than
five years, for planning ahead, for checking the lists a third time without
any objection, for giving me a call at the right time so that I dont forget
something important, and for always being loyal.
Maher Khaldi, for generously sharing everything you value, including your
knowledge and skills about depression and ECT, your bookshelf, and 60%
of Ann-charlotte. For signing all the papers I gave you, for informing and
preparing your patients for inclusion in the studies, and for making the
effort to comb their hair for unilateral treatment.
71
Fides Schckher Ugge, my clinical supervisor, for regularly giving me advice from your mature personality. It is inspiring to see you build mutual
confidence with patients, and combine pharmacotherapy and aspects of
psychotherapy into good practice. Furthermore, it is good to know that it
is possible to be a clinician in psychiatry for many years without becoming
disillusioned.
Ole Brus, Emil Gustafsson, Anders Magnusson, Ruzan Udumyan, and
Scott Montgomery for your programming and for helping with various
statistical issues.
Andreas Carlborg, Tomas Ljung, and Petros Koulouris for including patients in the clinical trial and also to Malgorzata Szmidt, Ioannis Pantziaras
and Ing-Marie Daniels for your collaboration in the initial phase of the
trial.
Jan Jones and Marie Johansson, for your good mood, for taking care of the
patients in the studies, for filling out forms, and for nagging the doctors to
do the assessments. Per Sderberg for your commitment to this research.
Maria Blom, Ulrica Fagerberg-Lavn, Mns Reichenwallner, Erika Aretis,
and all others involved in the quality register and clinical trial for your
collaboration.
Lars Kjellin for a straightforward and confiding leadership. Anna Wadefjord, for keeping papers in order, entering forms in the database, proofreading this manuscript and raising the spirits at the Psychiatric Research
Centre (PFC), and to all other companions at PFC including: Rickard Ahlberg, Tabita Bjrk, Suzanne Blomquist, Ferenc Blmel, Annika Norell
Clarke, Marie Elvin, Maria Fogelkvist, Sanna Aila Gustafsson, Mona Wilhelmsson Gstas, Fredrik Hollndare, Mats Humble, Sara Larsson, Katarina Lindstedt, Mikael Selvin, Kerstin Neander, Veikko Pelto-Piri, Agneta
Schrder and Kurt Skrberg; each of you contributed time and effort to
improve this thesis. Together you form an open and creative environment
where different perspectives on various research questions can be shared in
a positive way.
Birgitta Johansson Huuva, Anders Mrtensson, Bjrn-Erik Thaln, Martin
Flodin, Yvonne Danielsson, Petra Reuling, and Daniel Jansson Hammargren for supporting our work with quality registration, improvement and
research.
72
Affektiva mottagningen, for your part of the treatments with lithium and
ECT and to the doctors and nurses that delivered the anaesthesia including
Jan Halln, and the nurses at A-huset.
Georgios Alexopoulos, for delivering ECT, for establishing very good contact with the patients and for making assessments during the summer.
Daniel Tsehay for keeping your hands out of my pockets, and all other
colleagues at the psychiatric department for taking good care of the patients and for completing those extra forms.
Marie sberg, Gran Isacsson and Jayanti Chotai for coming to rebro
for seminars and for suggestions that improved this thesis.
Caroline Kalerud at the Swedish Social Insurance Agency and Pernilla
Fagerstrm at The National Board for Health and Welfare for providing
data.
Margareta Landin for good library service and for arranging Endnote
styles.
Tonny Andersn, Ralph Ansjn, Niclas Bengtsson, Ullvi Bve, Martin
Hultn, Aki Johanson, Jussi Jokinen, Mikael Landn, Johan Lundberg, and
Pia Nordanskog at the Quality register for your inputs in to the clinical
aspects of ECT, research, and improvement of standards. Also, I especially
thank Pia for collaborating with me on the guidelines for ECT and lending
me some background material. I enjoy working with you all.
Kristina Duberg, Christina Edvardsson, Tove Elvin, Anna Jakobsson, Tage
Johansson, and Angela Petersson, for various good work with the quality
register.
I would like to thank rebro University and the School of Health and
Medical Sciences for providing a good framework and environment for my
research. I am grateful for the professional support provided by Ann-Britt
Ivarsson and sa Berglind.
Bodil Klintberg, Ing-Marie Wieselgren, Ulrika Frithiofsson, Anna Folkegrd, among others at Swedish Association of Local Authorities and Regions, for financial and other support of the quality register. The research
was also supported financially by the Uppsala-rebro Regional Research
73
Council, the rebro County Council Research Committee, the Psychiatric

Research Centre, and the participating clinics.
Kristina Lindwall Sundel, and others in the little group for improving
the clarity of the variables in the register and a special thanks to Mattias
Agestam for making the journal register integration a reality.
Everyone at KCP including Carl Lago for spreading your enthusiasm and
visions of the future and Anneli Kragh, for wonderful help with the official
statistics.
Lise-Lotte Ris Bergerlind and Dan Gothefors among others at the Swedish Psychiatric Association and to Mrten Gerle for supporting the quality
register and coming guidelines.
Ann-charlotte Sundh Persson for practical details.
My friends, for occasionally managing to take me out of my bubble.
My family, including Eva, Dag and Anna, for letting the last little brother
be first.
Bo and Kerstin, my parents, for always being ready to go to rebro to do
what ever it takes for me and my family. It is a great comfort to know that
you are always there.
Anna, my wife, for being beautiful and kind, for giving birth to our daughters, and for taking good care of them while I sit in front of my computer.
Lina, Lovisa and Sara, my three daughters, for providing a meaning to life.
74
REFERENCES
1.
Abrams R, editor. Electroconvulsive Therapy: Oxford
University Press; 2002.
2.
American Psychiatric Association. Diagnostic and statistical
manual of mental disorders (4th ed., text rev.). Washington: American
Psychiatric Association; 2000.
3.
Andersn T, Bengtsson N, Hultn M, Landn M, Lundberg
J, Nordanskog P, Nordenskjld A, von Knorring L. rsrapport
Kvalitetsregister ECT 2011.
4.
Angst J, Preisig M. Course of a clinical cohort of unipolar,
bipolar and schizoaffective patients. Results of a prospective study from
1959 to 1985. Schweiz Arch Neurol Psychiatr. 1995;146(1):5-16. Epub
1995/01/01.
5.
Austin MP, Mitchell P, Goodwin GM. Cognitive deficits in
depression: possible implications for functional neuropathology. Br J
Psychiatry. 2001;178:200-6. Epub 2001/03/07.
6.
Bauer M, Bschor T, Kunz D, Berghofer A, Strohle A,
Muller-Oerlinghausen B. Double-blind, placebo-controlled trial of the use
of lithium to augment antidepressant medication in continuation treatment
of unipolar major depression. Am J Psychiatry. 2000;157(9):1429-35.
Epub 2000/08/31.
7.
Bauer M, Dopfmer S. Lithium augmentation in treatmentresistant depression: meta-analysis of placebo-controlled studies. J Clin
Psychopharmacol. 1999;19(5):427-34. Epub 1999/10/03.
8.
Beauchamp TL, Childress JF. Principles of biomedical
ethics. 5th ed. New York, N.Y.: Oxford University Press; 2001. ISBN
0195143310 (alk. paper)
9.
Beck AT. The current state of cognitive therapy: a 40-year
retrospective. Arch Gen Psychiatry. 2005;62(9):953-9. Epub 2005/09/07.
10.
Belmaker RH, Agam G. Major depressive disorder. N Engl
J Med. 2008;358(1):55-68. Epub 2008/01/04.
11.
Bergsholm P. Patients' perspectives on electroconvulsive
therapy: a reevaluation of the review by Rose et al on memory loss after
electroconvulsive therapy. J ECT. 2012;28(1):27-30. Epub 2012/02/22.
12.
Bora E, Yucel M, Pantelis C. Cognitive impairment in
affective psychoses: a meta-analysis. Schizophr Bull. 2010;36(1):112-25.
Epub 2009/09/22.
13.
Bowdler JM, Green AR, Minchin MC, Nutt DJ. Regional
GABA concentration and [3H]-diazepam binding in rat brain following
repeated electroconvulsive shock. J Neural Transm. 1983;56(1):3-12. Epub
1983/01/01.
75
14.
Brady EU, Kendall PC. Comorbidity of anxiety and
depression in children and adolescents. Psychol Bull. 1992;111(2):244-55.
Epub 1992/03/01.
15.
Castren E, Rantamaki T. The role of BDNF and its
receptors in depression and antidepressant drug action: Reactivation of
developmental plasticity. Dev Neurobiol. 2010;70(5):289-97. Epub
2010/02/27.
16.
Chen J, Gao K, Kemp DE. Second-generation antipsychotics
in major depressive disorder: update and clinical perspective. Curr Opin
Psychiatry. 2011;24(1):10-7. Epub 2010/11/20.
17.
Cronholm B, Ottosson JO. Memory functions in
endogenous depression before and after electroconvulsive therapy. Arch
Gen Psychiatry. 1961;5:193-9. Epub 1961/08/01.
18.
Cronholm B, Ottosson JO. Ultrabrief Stimulus Technique in
Electroconvulsive Therapy. Ii. Comparative Studies of Therapeutic Effects
and Memory Disturbances in Treatment of Endogenous Depression with
the Elther Es Electroshock Apparatus and Siemens Konvulsator Iii. J Nerv
Ment Dis. 1963;137:268-76. Epub 1963/09/01.
19.
d'Elia G. Unilateral electroconvulsive therapy. Acta
Psychiatr Scand Suppl. 1970;215:1-98. Epub 1970/01/01.
20.
d'Elia G, Lorentzson S, Raotma H, Widepalm K.
Comparison of unilateral dominant and non-dominant ECT on verbal and
non-verbal memory. Acta Psychiatr Scand. 1976;53(2):85-94. Epub
1976/02/01.
21.
d'Elia G, Raotma H. Is unilateral ECT less effective than
bilateral ECT? Br J Psychiatry. 1975;126:83-9. Epub 1975/01/01.
22.
Davis LL, Wisniewski SR, Howland RH, Trivedi MH,
Husain MM, Fava M, McGrath PJ, Balasubramani GK, Warden D, Rush
AJ. Does comorbid substance use disorder impair recovery from major
depression with SSRI treatment? An analysis of the STAR*D level one
treatment outcomes. Drug Alcohol Depend. 2010;107(2-3):161-70. Epub
2009/12/01.
23.
de Vreede IM, Burger H, van Vliet IM. Prediction of
response to ECT with routinely collected data in major depression. J Affect
Disord. 2005;86(2-3):323-7. Epub 2005/06/07.
24.
DeCarli C, Kawas C, Morrison JH, Reuter-Lorenz PA,
Sperling RA, Wright CB. Session II: Mechanisms of age-related cognitive
change and targets for intervention: neural circuits, networks, and
plasticity. J Gerontol A Biol Sci Med Sci. 2012;67(7):747-53. Epub
2012/05/10.
25.
Depp CA, Mausbach BT, Bowie C, Wolyniec P, Thornquist
MH, Luke JR, McGrath JA, Pulver AE, Harvey PD, Patterson TL.
Determinants of occupational and residential functioning in bipolar
disorder. J Affect Disord. 2012;136(3):812-8. Epub 2011/12/02.
76
26.
Dombrovski AY, Mulsant BH, Haskett RF, Prudic J, Begley
AE, Sackeim HA. Predictors of remission after electroconvulsive therapy in
unipolar major depression. J Clin Psychiatry. 2005;66(8):1043-9.
27.
Eaton WW, Shao H, Nestadt G, Lee HB, Bienvenu OJ,
Zandi P. Population-based study of first onset and chronicity in major
depressive disorder. Arch Gen Psychiatry. 2008;65(5):513-20. Epub
2008/05/07.
28.
Fall PA, Ekman R, Granerus AK, Thorell LH, Walinder J.
ECT in Parkinson's disease. Changes in motor symptoms, monoamine
metabolites and neuropeptides. J Neural Transm Park Dis Dement Sect.
1995;10(2-3):129-40. Epub 1995/01/01.
29.
Fink M. Predictors of outcome in convulsive therapy.
Psychopharmacol Bull. 1982;18(2):50-7. Epub 1982/04/01.
30.
Fink M. Convulsive therapy: a review of the first 55 years. J
Affect Disord. 2001;63(1-3):1-15. Epub 2001/03/14.
31.
Folstein MF, Folstein SE, McHugh PR. "Mini-mental
state". A practical method for grading the cognitive state of patients for the
clinician. J Psychiatr Res. 1975;12(3):189-98. Epub 1975/11/01.
32.
Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S,
Amsterdam JD, Shelton RC, Fawcett J. Antidepressant drug effects and
depression severity: a patient-level meta-analysis. JAMA. 2010;303(1):4753. Epub 2010/01/07.
33.
Frank E, Karp JF, Rush AJ. Efficacy of treatments for major
depression. Psychopharmacol Bull. 1993;29(4):457-75. Epub 1993/01/01.
34.
Fraser LM, O'Carroll RE, Ebmeier KP. The effect of
electroconvulsive therapy on autobiographical memory: a systematic
review. J ECT. 2008;24(1):10-7. Epub 2008/04/02.
35.
Fuster JM. The prefrontal cortex--an update: time is of the
essence. Neuron. 2001;30(2):319-33. Epub 2001/06/08.
36.
Gagne GG, Jr., Furman MJ, Carpenter LL, Price LH.
Efficacy of continuation ECT and antidepressant drugs compared to longterm antidepressants alone in depressed patients. Am J Psychiatry.
2000;157(12):1960-5.
37.
Gaudiano BA, Beevers CG, Miller IW. Differential response
to combined treatment in patients with psychotic versus nonpsychotic
major depression. J Nerv Ment Dis. 2005;193(9):625-8. Epub 2005/09/01.
38.
Gilman SE, Abraham HD. A longitudinal study of the order
of onset of alcohol dependence and major depression. Drug Alcohol
Depend. 2001;63(3):277-86. Epub 2001/06/22.
39.
Gonda X, Pompili M, Serafini G, Montebovi F, Campi S,
Dome P, Duleba T, Girardi P, Rihmer Z. Suicidal behavior in bipolar
disorder: epidemiology, characteristics and major risk factors. J Affect
Disord. 2012;143(1-3):16-26. Epub 2012/07/06.
77
40.
Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW,
Moller HJ, Kasper S. The World Federation of Societies of Biological
Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar
Disorders: Update 2010 on the treatment of acute bipolar depression.
World J Biol Psychiatry. 2010;11(2):81-109. Epub 2010/02/13.
41.
Guy
W.
ECDEU
assessment
manual
for
psychopharmacology. Rockville, MD, National Institute of Health,
Psychopharmacology Research Branch; 1976. p. 21722.
42.
Hamilton M. A rating scale for depression. J Neurol
Neurosurg Psychiatry. 1960;23:56-62. Epub 1960/02/01.
43.
Hammar A, Ardal G. Cognitive functioning in major
depression--a summary. Frontiers in human neuroscience. 2009;3:26. Epub
2009/10/15.
44.
Hees HL, Koeter MW, Schene AH. Longitudinal
relationship between depressive symptoms and work outcomes in clinically
treated patients with long-term sickness absence related to major
depressive disorder. J Affect Disord. 2013. Epub 2013/01/22.
45.
Heikman P, Katila H, Sarna S, Wahlbeck K, Kuoppasalmi
K. Differential response to right unilateral ECT in depressed patients:
impact of comorbidity and severity of illness [ISRCTN39974945]. BMC
Psychiatry. 2002;2:2.
46.
Hellsten J, West MJ, Arvidsson A, Ekstrand J, Jansson L,
Wennstrom M, Tingstrom A. Electroconvulsive seizures induce
angiogenesis in adult rat hippocampus. Biol Psychiatry. 2005;58(11):8718. Epub 2005/07/27.
47.
Hensing G, Wahlstrom R. Swedish Council on Technology
Assessment in Health Care (SBU). Chapter 7. Sickness absence and
psychiatric disorders. Scandinavian journal of public health Supplement.
2004;63:152-80. Epub 2004/10/30.
48.
Holmberg G, Thesleff S. [Succinyl choline iodide as a
muscle relaxant in electroshock]. Nord Med. 1951;46(42):1567-70. Epub
1951/10/17. Succinylkolinjodid som muskelavslappande medel vid
elektroshockbehandling.
49.
Howland RH, Rush AJ, Wisniewski SR, Trivedi MH,
Warden D, Fava M, Davis LL, Balasubramani GK, McGrath PJ, Berman
SR. Concurrent anxiety and substance use disorders among outpatients
with major depression: clinical features and effect on treatment outcome.
Drug Alcohol Depend. 2009;99(1-3):248-60. Epub 2008/11/07.
50.
Huuhka M, Korpisammal L, Haataja R, Leinonen E. Oneyear outcome of elderly inpatients with major depressive disorder treated
with ECT and antidepressants. J ECT. 2004;20(3):179-85. Epub
2004/09/03.
78
51.
Inskip HM, Harris EC, Barraclough B. Lifetime risk of
suicide for affective disorder, alcoholism and schizophrenia. Br J
Psychiatry. 1998;172:35-7. Epub 1998/04/16.
52.
Isacsson G, Holmgren A, Osby U, Ahlner J. Decrease in
suicide among the individuals treated with antidepressants: a controlled
study of antidepressants in suicide, Sweden 1995-2005. Acta Psychiatr
Scand. 2009;120(1):37-44. Epub 2009/02/19.
53.
Isometsa E, Aro S, Aro H. Depression in Finland: a
computer assisted telephone interview study. Acta Psychiatr Scand.
1997;96(2):122-8. Epub 1997/08/01.
54.
Kantor SJ, Glassman AH. Delusional depressions: natural
history and response to treatment. Br J Psychiatry. 1977;131:351-60. Epub
1977/10/01.
55.
Keller MB, Lavori PW, Mueller TI, Endicott J, Coryell W,
Hirschfeld RM, Shea T. Time to recovery, chronicity, and levels of
psychopathology in major depression. A 5-year prospective follow-up of
431 subjects. Arch Gen Psychiatry. 1992;49(10):809-16. Epub
1992/10/01.
56.
Kellner CH, Knapp R, Husain MM, Rasmussen K,
Sampson S, Cullum M, McClintock SM, Tobias KG, Martino C, Mueller
M, Bailine SH, Fink M, Petrides G. Bifrontal, bitemporal and right
unilateral electrode placement in ECT: randomised trial. Br J Psychiatry.
2010;196(3):226-34. Epub 2010/03/03.
57.
Kellner CH, Knapp RG, Petrides G, Rummans TA, Husain
MM, Rasmussen K, Mueller M, Bernstein HJ, O'Connor K, Smith G, Biggs
M, Bailine SH, Malur C, Yim E, McClintock S, Sampson S, Fink M.
Continuation Electroconvulsive Therapy vs Pharmacotherapy for Relapse
Prevention in Major Depression: A Multisite Study From the Consortium
for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry.
2006;63(12):1337-44.
58.
Kessler RC, Berglund P, Demler O, Jin R, Koretz D,
Merikangas KR, Rush AJ, Walters EE, Wang PS. The epidemiology of
major depressive disorder: results from the National Comorbidity Survey
Replication (NCS-R). JAMA. 2003;289(23):3095-105. Epub 2003/06/19.
59.
Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes
M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month
prevalence of DSM-III-R psychiatric disorders in the United States. Results
from the National Comorbidity Survey. Arch Gen Psychiatry.
1994;51(1):8-19. Epub 1994/01/01.
60.
Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM,
Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid
risk of anxiety and mood disorders in the United States. International
journal of methods in psychiatric research. 2012;21(3):169-84. Epub
2012/08/07.
79
61.
Khan A, Leventhal RM, Khan SR, Brown WA. Severity of
depression and response to antidepressants and placebo: an analysis of the
Food and Drug Administration database. J Clin Psychopharmacol.
2002;22(1):40-5. Epub 2002/01/19.
62.
Kho KH, Zwinderman AH, Blansjaar BA. Predictors for the
efficacy of electroconvulsive therapy: chart review of a naturalistic study. J
Clin Psychiatry. 2005;66(7):894-9.
63.
Kindler S, Shapira B, Hadjez J, Abramowitz M, Brom D,
Lerer B. Factors Influencing Response to Bilateral Electroconvulsive
Therapy in Major Depression. Convuls Ther. 1991;7(4):245-54. Epub
1991/01/01.
64.
Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht
S. Second-generation antipsychotics for major depressive disorder and
dysthymia. Cochrane Database Syst Rev. 2010(12):CD008121. Epub
2010/12/15.
65.
Lambert G, Johansson M, Agren H, Friberg P. Reduced
brain norepinephrine and dopamine release in treatment-refractory
depressive illness: evidence in support of the catecholamine hypothesis of
mood disorders. Arch Gen Psychiatry. 2000;57(8):787-93. Epub
2000/08/02.
66.
Leiknes KA, Jarosh-von Schweder L, Hoie B. Contemporary
use and practice of electroconvulsive therapy worldwide. Brain and
behavior. 2012;2(3):283-344. Epub 2012/06/29.
67.
Lezak MD. Neuropsychological assessment. 5th ed. Oxford
; New York: Oxford University Press; 2012. ISBN 9780195395525
(hardcover alk. paper)
68.
Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K.
The UKU side effect rating scale. A new comprehensive rating scale for
psychotropic drugs and a cross-sectional study of side effects in
neuroleptic-treated patients. Acta Psychiatr Scand Suppl. 1987;334:1-100.
Epub 1987/01/01.
69.
Lippman S, Manshadi M, Wehry M, Byrd R, Past W, Keller
W, Schuster J, Elam S, Meyer D, O'Daniel R. 1,250 electroconvulsive
treatments without evidence of brain injury. Br J Psychiatry.
1985;147:203-4.
70.
Lisanby SH, Sampson S, Husain MM, Petrides G, Knapp
RG, McCall V, Young RC, Prudic J, Kellner CH. Toward individualized
post-electroconvulsive therapy care: piloting the Symptom-Titrated,
Algorithm-Based Longitudinal ECT (STABLE) intervention. The journal of
ECT. 2008;24(3):179-82. Epub 2008/08/19.
71.
Lloyd C. Life events and depressive disorder reviewed. I.
Events as predisposing factors. Arch Gen Psychiatry. 1980;37(5):529-35.
Epub 1980/05/01.
80
72.
Loo CK, Katalinic N, Martin D, Schweitzer I. A review of
ultrabrief pulse width electroconvulsive therapy. Therapeutic advances in
chronic disease. 2012;3(2):69-85. Epub 2012/12/20.
73.
Loo CK, Mahon M, Katalinic N, Lyndon B, Hadzi-Pavlovic
D. Predictors of response to ultrabrief right unilateral electroconvulsive
therapy. J Affect Disord. 2011;130(1-2):192-7. Epub 2010/10/22.
74.
Madsen TM, Treschow A, Bengzon J, Bolwig TG, Lindvall
O, Tingstrom A. Increased neurogenesis in a model of electroconvulsive
therapy. Biol Psychiatry. 2000;47(12):1043-9. Epub 2000/06/23.
75.
Martinez-Amoros E, Cardoner N, Soria V, Galvez V,
Menchon JM, Urretavizcaya M. Long-term treatment strategies in major
depression: a 2-year prospective naturalistic follow-up after successful
76.
McDermott LM, Ebmeier KP. A meta-analysis of depression
severity and cognitive function. J Affect Disord. 2009;119(1-3):1-8. Epub
2009/05/12.
77.
McDonald A, Walter G. Hollywood and ECT. Int Rev
Psychiatry. 2009;21(3):200-6. Epub 2009/05/22.
78.
McGrath PJ, Stewart JW, Quitkin FM, Chen Y, Alpert JE,
Nierenberg AA, Fava M, Cheng J, Petkova E. Predictors of relapse in a
prospective study of fluoxetine treatment of major depression. A J
Psychiatry. 2006;163(9):1542-8. Epub 2006/09/02.
79.
McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R,
Cardno A. The heritability of bipolar affective disorder and the genetic
relationship to unipolar depression. Arch Gen Psychiatry. 2003;60(5):497502. Epub 2003/05/14.
80.
McKay MS, Zakzanis KK. The impact of treatment on HPA
axis activity in unipolar major depression. J Psychiatr Res.
2010;44(3):183-92. Epub 2009/09/15.
81.
McNally KA, Blumenfeld H. Focal network involvement in
generalized seizures: new insights from electroconvulsive therapy. Epilepsy
& behavior : E&B. 2004;5(1):3-12. Epub 2004/01/31.
82.
Mintz J, Mintz LI, Arruda MJ, Hwang SS. Treatments of
depression and the functional capacity to work. Arch Gen Psychiatry.
1992;49(10):761-8. Epub 1992/10/01.
83.
Mohs RC, Cohen L. Alzheimer's Disease Assessment Scale
(ADAS). Psychopharmacol Bull. 1988;24(4):627-8. Epub 1988/01/01.
84.
Moksnes KM. Relapse following electroconvulsive therapy.
Tidsskr Nor Laegeforen. 2011;131(20):1991-3. Epub 2011/10/22.
85.
Montgomery SA, Asberg M. A new depression scale
designed to be sensitive to change. Br J Psychiatry. 1979;134:382-9.
86.
Munk-Olsen T, Laursen TM, Videbech P, Mortensen PB,
Rosenberg R. All-cause mortality among recipients of electroconvulsive
therapy: register-based cohort study. Br J Psychiatry. 2007;190:435-9.
81
87.
Navarro V, Gasto C, Torres X, Masana G, Penades R,
Guarch J, Vazquez M, Serra M, Pujol N, Pintor L, Catalan R.
Continuation/maintenance treatment with nortriptyline versus combined
nortriptyline and ECT in late-life psychotic depression: a two-year
randomized study. Am J Geriatr Psychiatry. 2008;16(6):498-505. Epub
2008/06/03.
88.
Nelson JC, Papakostas GI. Atypical antipsychotic
augmentation in major depressive disorder: a meta-analysis of placebocontrolled randomized trials. A J Psychiatry. 2009;166(9):980-91. Epub
2009/08/19.
89.
Newton-Howes G, Tyrer P, Johnson T. Personality disorder
and the outcome of depression: meta-analysis of published studies. Br J
Psychiatry. 2006;188:13-20. Epub 2006/01/03.
90.
NICE. Guidance on the use of electroconvulsive therapy
Service NH, editor. London: National Institute for Clinical Excellence;
2005. ISBN 1-84257-282-2
91.
NICE. The treatment and management of depression in
adults. London: National Institute for Clinical Excellence; 2009.
92.
Nierenberg AA, Husain MM, Trivedi MH, Fava M,
Warden D, Wisniewski SR, Miyahara S, Rush AJ. Residual symptoms after
remission of major depressive disorder with citalopram and risk of relapse:
a STAR*D report. Psychol Med. 2010;40(1):41-50. Epub 2009/05/23.
93.
Nordanskog P, Dahlstrand U, Larsson MR, Larsson EM,
Knutsson L, Johanson A. Increase in hippocampal volume after
electroconvulsive therapy in patients with depression: a volumetric
magnetic resonance imaging study. J ECT. 2010;26(1):62-7. Epub
2010/03/02.
94.
Nordanskog P, Nordenskjld A, Jarbin H, Lindberg C.
Swedish Psychiatric Association's Guidelines for ECT. Manuscript. 2013.
95.
Noulhiane M, Piolino P, Hasboun D, Clemenceau S, Baulac
M, Samson S. Autobiographical memory after temporal lobe resection:
neuropsychological and MRI volumetric findings. Brain. 2007;130(Pt
12):3184-99. Epub 2007/11/08.
96.
O'Connor MK, Knapp R, Husain M, Rummans TA,
Petrides G, Smith G, Mueller M, Snyder K, Bernstein H, Rush AJ, Fink M,
Kellner C. The influence of age on the response of major depression to
electroconvulsive therapy: a C.O.R.E. Report. Am J Geriatr Psychiatry.
2001;9(4):382-90.
97.
Odeberg H, Rodriguez-Silva B, Salander P, Martensson B.
Individualized continuation electroconvulsive therapy and medication as a
bridge to relapse prevention after an index course of electroconvulsive
therapy in severe mood disorders: a naturalistic 3-year cohort study. J
ECT. 2008;24(3):183-90.
82
98.
Ohman R, Walinder J, Balldin J, Wallin L. Prolactin
response to electroconvulsive therapy. Lancet. 1976;2(7992):936-7. Epub
1976/10/30.
99.
Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess
mortality in bipolar and unipolar disorder in Sweden. Arch Gen
Psychiatry. 2001;58(9):844-50. Epub 2001/09/26.
100.
Wiles N, Thomas L, Abel A, Ridgway N, Turner N,
Campbell J, Garland A, Hollinghurst S, Jerrom B, Kessler D, Kuyken W,
Morrison J, Turner K, Williams C, Peters T, Lewis G. Cognitive
behavioural therapy as an adjunct to pharmacotherapy for primary care
based patients with treatment resistant depression: results of the CoBalT
randomised controlled trial. Lancet. 2013;381(9864):375-84. Epub
2012/12/12.
101.
Ottosson J-O, Fink M. Ethics in electroconvulsive therapy.
New York: Brunner-Routledge; 2004. ISBN 041594659X (hardback)
102.
Ottosson JO. Experimental studies of the mode of action of
electroconvulsive therapy: Introduction. Acta Psychiatr Scand Suppl.
1960;35(145):5-6. Epub 1960/01/01.
103.
Ottosson JO, Odeberg H. Evidence-based electroconvulsive
therapy. Acta Psychiatr Scand. 2012;125(3):177-84. Epub 2012/02/14.
104.
Parker G, Roy K, Hadzi-Pavlovic D, Pedic F. Psychotic
(delusional) depression: a meta-analysis of physical treatments. J Affect
Disord. 1992;24(1):17-24. Epub 1992/01/01.
105.
Perrin JS, Merz S, Bennett DM, Currie J, Steele DJ, Reid IC,
Schwarzbauer C. Electroconvulsive therapy reduces frontal cortical
connectivity in severe depressive disorder. Proc Natl Acad Sci U S A.
2012;109(14):5464-8. Epub 2012/03/21.
106.
Petrides G, Fink M, Husain MM, Knapp RG, Rush AJ,
Mueller M, Rummans TA, O'Connor KM, Rasmussen KG, Jr., Bernstein
HJ, Biggs M, Bailine SH, Kellner CH. ECT remission rates in psychotic
versus nonpsychotic depressed patients: a report from CORE. J Ect.
2001;17(4):244-53.
107.
Ploski JE, Newton SS, Duman RS. Electroconvulsive
seizure-induced gene expression profile of the hippocampus dentate gyrus
granule cell layer. J Neurochem. 2006;99(4):1122-32. Epub 2006/11/04.
108.
Prudic J, Haskett RF, McCall WV, Isenberg K, Cooper T,
Rosenquist PB, Mulsant BH, Sackeim HA. Pharmacological Strategies in
the Prevention of Relapse After Electroconvulsive Therapy. J ECT.
2013;29(1):3-12. Epub 2013/01/11.
109.
Prudic J, Haskett RF, Mulsant B, Malone KM, Pettinati
HM, Stephens S, Greenberg R, Rifas SL, Sackeim HA. Resistance to
antidepressant medications and short-term clinical response to ECT. A J
Psychiatry. 1996;153(8):985-92.
83
110.
Prudic J, Olfson M, Marcus SC, Fuller RB, Sackeim HA.
Effectiveness of electroconvulsive therapy in community settings. Biol
Psychiatry. 2004;55(3):301-12.
111.
Prudic J, Olfson M, Sackeim HA. Electro-convulsive
therapy practices in the community. Psychol Med. 2001;31(5):929-34.
Epub 2001/07/19.
112.
Prudic J, Peyser S, Sackeim HA. Subjective memory
complaints: a review of patient self-assessment of memory after
electroconvulsive therapy. J Ect. 2000;16(2):121-32.
113.
Putnam FW. Ten-year research update review: child sexual
abuse. J Am Acad Child Adolesc Psychiatry. 2003;42(3):269-78. Epub
2003/02/22.
114.
Rabheru K. Maintenance electroconvulsive therapy (MECT) after acute response: examining the evidence for who, what, when,
and how? J ECT. 2012;28(1):39-47. Epub 2012/02/15.
115.
Rasmussen KG. Sham electroconvulsive therapy studies in
depressive illness: a review of the literature and consideration of the
placebo phenomenon in electroconvulsive therapy practice. J ECT.
2009;25(1):54-9. Epub 2008/06/27.
116.
Rasmussen KG, Mueller M, Rummans TA, Husain MM,
Petrides G, Knapp RG, Fink M, Sampson SM, Bailine SH, Kellner CH. Is
baseline medication resistance associated with potential for relapse after
successful remission of a depressive episode with ECT? Data from the
Consortium for Research on Electroconvulsive Therapy (CORE). J Clin
Psychiatry. 2009;70(2):232-7.
117.
Reid M, Parkinson L, Gibson R, Schofield P, D'Este C,
Attia J, Tavener M, Byles J. Memory complaint questionnaire performed
poorly as screening tool: validation against psychometric tests and affective
measures. J Clin Epidemiol. 2012;65(2):199-205. Epub 2011/09/06.
118.
Reid S, Barbui C. Long term treatment of depression with
selective serotonin reuptake inhibitors and newer antidepressants. BMJ.
2010;340:c1468. Epub 2010/03/30.
119.
Robins LN, Regier DA. Psychiatric disorders in America :
the epidemiologic catchment area study. New York Toronto: Free Press;
Collier Macmillan Canada; Maxwell Macmillan International; 1991. ISBN
0029265711
120.
Rorsman B, Grasbeck A, Hagnell O, Lanke J, Ohman R,
Ojesjo L, Otterbeck L. A prospective study of first-incidence depression.
The Lundby study, 1957-72. Br J Psychiatry. 1990;156:336-42. Epub
1990/03/01.
121.
Rorsman B, Hagnell O, Lanke J. Mortality and hidden
mental disorder in the Lundby Study. Age-standardized death rates among
mentally ill 'non-patients' in a total population observed during a 25-year
period. Neuropsychobiology. 1983;10(2-3):83-9. Epub 1983/01/01.
84
122.
Rush AJ, Thase ME, Dube S. Research issues in the study of
difficult-to-treat depression. Biol Psychiatry. 2003;53(8):743-53. Epub
2003/04/23.
123.
Russell JC, Rasmussen KG, O'Connor MK, Copeman CA,
Ryan DA, Rummans TA. Long-term maintenance ECT: a retrospective
review of efficacy and cognitive outcome. J Ect. 2003;19(1):4-9.
124.
Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann
JJ, Pettinati HM, Greenberg RM, Crowe RR, Cooper TB, Prudic J.
Continuation pharmacotherapy in the prevention of relapse following
electroconvulsive therapy: a randomized controlled trial. Jama.
2001;285(10):1299-307.
125.
Sackeim HA, Prudic J, Devanand DP, Decina P, Kerr B,
Malitz S. The impact of medication resistance and continuation
pharmacotherapy on relapse following response to electroconvulsive
therapy in major depression. J Clin Psychopharmacol. 1990;10(2):96-104.
126.
Sackeim HA, Prudic J, Devanand DP, Kiersky JE,
Fitzsimons L, Moody BJ, McElhiney MC, Coleman EA, Settembrino JM.
Effects of stimulus intensity and electrode placement on the efficacy and
cognitive effects of electroconvulsive therapy. N Engl J Med.
1993;328(12):839-46.
127.
Sackeim HA, Prudic J, Fuller R, Keilp J, Lavori PW, Olfson
M. The cognitive effects of electroconvulsive therapy in community
settings. Neuropsychopharmacology. 2007;32(1):244-54.
128.
Sackeim HA, Prudic J, Nobler MS, Fitzsimons L, Lisanby
SH, Payne N, Berman RM, Brakemeier EL, Perera T, Devanand DP.
Effects of pulse width and electrode placement on the efficacy and
cognitive effects of electroconvulsive therapy. Brain stimulation.
2008;1(2):71-83. Epub 2008/04/01.
129.
Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ,
Ostroff RB, Berman RM, Krystal JH. Increased cortical GABA
concentrations in depressed patients receiving ECT. The American journal
of psychiatry. 2003;160(3):577-9. Epub 2003/03/04.
130.
Sareen J, Enns MW, Guertin JE. The impact of clinically
diagnosed personality disorders on acute and one-year outcomes of
131.
Sartorius A, Wolf J, Henn FA. Lithium and ECT-concurrent use still demands attention: three case reports. World J Biol
Psychiatry. 2005;6(2):121-4.
132.
SBU. Behandling av depressionssjukdomar, volym 1. En
systematisk litteraturversikt. Stockholm: Statens beredning fr medicinsk
utvrdering (SBU) 2004. SBU-rapport nr 166/1. ISBN 91-87890-87-9
133.
systematisk litteraturversikt. Stockholm: Statens beredning for medicinsk
utvrdering (SBU) 2004. SBU-rapport nr 166/2. ISBN 91-87890-88-7
85
134.
systematisk litteraturversikt. Stockholm: Statensberedning fr medicinsk
utvrdering (SBU). 2004. SBU-rapport nr 166/3. ISBN 91-87890-94-1
135.
Schmid M, Strand M, Ardal G, Lund A, Hammar A.
Prolonged impairment in inhibition and semantic fluency in a follow-up
study of recurrent major depression. Archives of clinical neuropsychology :
the official journal of the National Academy of Neuropsychologists.
2011;26(7):677-86. Epub 2011/06/28.
136.
Schwarz T, Loewenstein J, Isenberg KE. Maintenance ECT:
indications and outcome. Convuls Ther. 1995;11(1):14-23. Epub
1995/03/01.
137.
Semkovska M, McLoughlin DM. Objective cognitive
performance associated with electroconvulsive therapy for depression: a
systematic review and meta-analysis. Biol Psychiatry. 2010;68(6):568-77.
Epub 2010/08/03.
138.
Semkovska M, McLoughlin DM. Measuring Retrograde
Autobiographical Amnesia Following Electroconvulsive Therapy:
Historical Perspective and Current Issues. J ECT. 2013. Epub 2013/01/11.
139.
Semkovska M, Noone M, Carton M, McLoughlin DM.
Measuring consistency of autobiographical memory recall in depression.
Psychiatry Res. 2012;197(1-2):41-8. Epub 2012/03/09.
140.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs
J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International
Neuropsychiatric Interview (M.I.N.I.): the development and validation of a
structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin
Psychiatry. 1998;59 Suppl 20:22-33;quiz 4-57. Epub 1999/01/09.
141.
Shorter E, Healy D. Shock therapy: a history of
electroconvulsive therapy in mental illness. Piscataway: Rutgers University
Press; 2007. ISBN 978-0-8135-4169-3
142.
Sinyor M, Schaffer A, Levitt A. The sequenced treatment
alternatives to relieve depression (STAR*D) trial: a review. Can J
Psychiatry. 2010;55(3):126-35. Epub 2010/04/08.
143.
Sirey JA, Bruce ML, Alexopoulos GS, Perlick DA, Friedman
SJ, Meyers BS. Stigma as a barrier to recovery: Perceived stigma and
patient-rated severity of illness as predictors of antidepressant drug
adherence. Psychiatr Serv. 2001;52(12):1615-20. Epub 2001/12/01.
144.
Smit F, Cuijpers P, Oostenbrink J, Batelaan N, de Graaf R,
Beekman A. Costs of nine common mental disorders: implications for
curative and preventive psychiatry. The journal of mental health policy and
economics. 2006;9(4):193-200. Epub 2007/01/04.
145.
Smith GE, Rasmussen KG, Cullum CM, Felmlee-Devine
MD, Petrides G, Rummans TA, Husain MM, Mueller M, Bernstein HJ,
Knapp RG, O'Connor MK, Fink M, Sampson S, Bailine SH, Kellner CH. A
randomized controlled trial comparing the memory effects of continuation
86
electroconvulsive therapy versus continuation pharmacotherapy: results

from the consortium for research in ECT (CORE) study. J Clin Psychiatry.
2010;71(2):185-93. Epub 2010/03/03.
146.
Sobin C, Prudic J, Devanand DP, Nobler MS, Sackeim HA.
Who responds to electroconvulsive therapy? A comparison of effective and
ineffective forms of treatment. Br J Psychiatry. 1996;169(3):322-8.
147.
Socialstyrelsen. ICD-10 Swedish version, Klassifikation av
sjukdomar och hlsoproblem. Stockholm: Socialstyrelsen, National Board
of Health and Welfare; 1997.
148.
Socialstyrelsen.
Depression
och
ngestsyndrom
Vetenskapligt underlag fr nationella riktlinjer. Stockholm 2010.
149.
Socialstyrelsen. Pharmaceuticals statistics for 2010:
Socialstyrelsen. National Board of Health and Welfare; 2011. ISBN 97891-86585-96-9
150.
Socialstyrelsen. Causes of Death 2011. Stockholm:
Socialstyrelsen. National Board of Health and Welfare; 2012. ISBN 97891-7555-039-8
151.
Squire LR, Slater PC. Electroconvulsive therapy and
complaints of memory dysfunction: a prospective three-year follow-up
study. Br J Psychiatry. 1983;142:1-8. Epub 1983/01/01.
152.
Stahl SM. Depression and bipolar disorder : Stahl's essential
psychopharmacology. 3rd ed. Cambridge ; New York: Cambridge
University Press; 2008. ISBN 9780521886635 (hardcover)
153.
Stoudemire A, Hill CD, Dalton ST, Marquardt MG.
Rehospitalization rates in older depressed adults after antidepressant and
electroconvulsive therapy treatment. J Am Geriatr Soc. 1994;42(12):12825.
154.
Stromgren LS, Crhristensen AL, Fromholt P. The effects of
unilateral brief-interval ECT on memory. Acta Psychiatr Scand.
1976;54(5):336-46. Epub 1976/11/01.
155.
Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology
of major depression: review and meta-analysis. Am J Psychiatry.
2000;157(10):1552-62. Epub 2000/09/29.
156.
Svanborg P, Asberg M. A comparison between the Beck
Depression Inventory (BDI) and the self-rating version of the Montgomery
Asberg Depression Rating Scale (MADRS). J Affect Disord. 2001;64(23):203-16. Epub 2001/04/21.
157.
Swoboda E, Conca A, Konig P, Waanders R, Hansen M.
Maintenance electroconvulsive therapy in affective and schizoaffective
disorder. Neuropsychobiology. 2001;43(1):23-8.
158.
Taylor MA, Fink M. Melancholia : the diagnosis,
pathophysiology, and treatment of depressive illness. Cambridge ; New
York: Cambridge University Press; 2006. ISBN 9780521841511 (hbk.)
87
159.
ten Doesschate MC, Bockting CL, Koeter MW, Schene AH.
Prediction of recurrence in recurrent depression: a 5.5-year prospective
study. J Clin Psychiatry. 2010;71(8):984-91. Epub 2010/08/28.
160.
Tew JD, Jr., Mulsant BH, Haskett RF, Joan P, Begley AE,
Sackeim HA. Relapse during continuation pharmacotherapy after acute
response to ECT: a comparison of usual care versus protocolized
treatment. Ann Clin Psychiatry. 2007;19(1):1-4.
161.
Tharyan P, Adams CE. Electroconvulsive therapy for
schizophrenia. Cochrane Database Syst Rev. 2005(2):CD000076. Epub
2005/04/23.
162.
The Swedish Social Insurance Agency. Social Insurance
Report -What are the costs for different diseases in Swedish sickness
insurance? 2011.
163.
Theodorsson E, Mathe AA, Stenfors C. Brain
neuropeptides: tachykinins, neuropeptide Y, neurotensin and vasoactive
intestinal polypeptide in the rat brain: modifications by ECT and
indomethacin.
Prog
Neuropsychopharmacol
Biol
Psychiatry.
1990;14(3):387-407. Epub 1990/01/01.
164.
The APA Task Force on Electroconvulsive therapy. The
practice of electroconvulsive therapy- recommendations for treatment,
training, and privileging. 2:nd edition ed. Washington D.C.: American
Psychiatric Publishing; 2001. ISBN 0-89042-206-0
165.
UK ECT Review Group. Efficacy and safety of
electroconvulsive therapy in depressive disorders: a systematic review and
meta-analysis. Lancet. 2003;361(9360):799-808. Epub 2003/03/19.
166.
Ustun TB, Ayuso-Mateos JL, Chatterji S, Mathers C,
Murray CJ. Global burden of depressive disorders in the year 2000. The
British journal of psychiatry : the journal of mental science. 2004;184:38692. Epub 2004/05/05.
167.
Waern M. Suicide in late life. Gteborg: Gteborg
University; 2000.
168.
Vanelle JM, Loo H, Galinowski A, de Carvalho W, Bourdel
MC, Brochier P, Bouvet O, Brochier T, Olie JP. Maintenance ECT in
intractable manic-depressive disorders. Convuls Ther. 1994;10(3):195-205.
Epub 1994/09/01.
169.
Watts BV, Groft A, Bagian JP, Mills PD. An examination of
mortality and other adverse events related to electroconvulsive therapy
using a national adverse event report system. J ECT. 2011;27(2):105-8.
Epub 2010/10/23.
170.
World Health Organization. The ICD-10 classification of
the mental and behavioural disorders: Clinical descriptions and diagnostic
guidelines. Geneva: World Health Organization; 1992.
88
171.
Zhang J, Narr KL, Woods RP, Phillips OR, Alger JR,
Espinoza RT. Glutamate normalization with ECT treatment response in
major depression. Mol Psychiatry. 2012. Epub 2012/05/09.
172.
sgrd U. Suicide among swedish women. Stockholm:
Karolinska Institutet; 1990.
89
Publications in the series

rebro Studies in Medicine
1.
Bergemalm, Per-Olof (2004). Audiologic and cognitive long-term

sequelae from closed head injury.
2.
Jansson, Kjell (2004). Intraperitoneal Microdialysis.

Technique and Results.
3.
Windahl, Torgny (2004). Clinical aspects of laser treatment of

lichen sclerosus and squamous cell carcinoma of the penis.
4.
Carlsson, Per-Inge (2004). Hearing impairment and deafness.

Genetic and environmental factors interactions consequences.
A clinical audiological approach.
5.
Wgster, Dick (2005). CXCL16 and CD137 in Atherosclerosis.
6.
Jatta, Ken (2006). Inflammation in Atherosclerosis.
7.
Dreifaldt, Ann Charlotte (2006). Epidemiological Aspects on

Malignant Diseases in Childhood.
8.
Jurstrand, Margaretha (2006). Detection of Chlamydia trachomatis

and Mycoplasma genitalium by genetic and serological methods.
9.
Norn, Torbjrn (2006). Clostridium difficile, epidemiology and

antibiotic resistance.
10. Anderzn Carlsson, Agneta (2007). Children with Cancer Focusing

on their Fear and on how their Fear is Handled.
11. Ocaya, Pauline (2007). Retinoid metabolism and signalling in
vascular smooth muscle cells.
12. Nilsson, Andreas (2008). Physical activity assessed by accelerometry
in children.
13. Eliasson, Henrik (2008). Tularemia epidemiological, clinical and
diagnostic aspects.
14. Walldn, Jakob (2008). The influence of opioids on gastric function:
experimental and clinical studies.
15. Andrn, Ove (2008). Natural history and prognostic factors in
localized prostate cancer.
16. Svantesson, Mia (2008). Postpone death? Nurse-physician
perspectives and ethics rounds.
17. Bjrk, Tabita (2008). Measuring Eating Disorder Outcome

Definitions, dropouts and patients perspectives.
18. Ahlsson, Anders (2008). Atrial Fibrillation in Cardiac Surgery.
19. Parihar, Vishal Singh (2008). Human Listeriosis Sources and Routes.
20. Berglund, Carolina (2008). Molecular Epidemiology of MethicillinResistant Staphylococcus aureus. Epidemiological aspects of MRSA
and the dissemination in the community and in hospitals.
21. Nilsagrd, Ylva (2008). Walking ability, balance and accidental falls in
persons with Multiple Sclerosis.
22. Johansson, Ann-Christin (2008). Psychosocial factors in patients
with lumbar disc herniation: Enhancing postoperative outcome by
the identification of predictive factors and optimised physiotherapy.
23. Larsson, Matz (2008). Secondary exposure to inhaled tobacco
products.
24. Hahn-Strmberg, Victoria (2008). Cell adhesion proteins in different
invasive patterns of colon carcinoma: A morphometric and molecular
genetic study.
25. Bttiger, Anna (2008). Genetic Variation in the Folate Receptor-
and Methylenetetrahydrofolate Reductase Genes as Determinants
of Plasma Homocysteine Concentrations.
26. Andersson, Gunnel (2009). Urinary incontinence. Prevalence,
treatment seeking behaviour, experiences and perceptions among
persons with and without urinary leakage.
27. Elfstrm, Peter (2009). Associated disorders in celiac disease.
28. Skrberg, Kurt (2009). Anabolic-androgenic steroid users in treatment:
Social background, drug use patterns and criminality.
29. de Man Lapidoth, Joakim (2009). Binge Eating and Obesity Treatment
Prevalence, Measurement and Long-term Outcome.
30. Vumma, Ravi (2009). Functional Characterization of Tyrosine
and Tryptophan Transport in Fibroblasts from Healthy Controls,
Patients with Schizophrenia and Bipolar Disorder.
31. Jacobsson, Susanne (2009). Characterisation of Neisseria meningitidis
from a virulence and immunogenic perspective that includes variations
in novel vaccine antigens.
32. Allvin, Rene (2009). Postoperative Recovery. Development of a

Multi-Dimensional Questionnaire for Assessment of Recovery.
33. Hagnelius, Nils-Olof (2009). Vascular Mechanisms in Dementia
with Special Reference to Folate and Fibrinolysis.
34. Duberg, Ann-Sofi (2009). Hepatitis C virus infection. A nationwide
study of assiciated morbidity and mortality.
35. Sderqvist, Fredrik (2009). Health symptoms and potential effects on
the blood-brain and blood-cerebrospinal fluid barriers associated with
use of wireless telephones.
36. Neander, Kerstin (2009). Indispensable Interaction. Parents perspectives
on parentchild interaction interventions and beneficial meetings.
37. Ekwall, Eva (2009). Womens Experiences of Gynecological Cancer
and Interaction with the Health Care System through Different Phases
of the Disease.
38. Thulin Hedberg, Sara (2009). Antibiotic susceptibility and resistance
in Neisseria meningitidis phenotypic and genotypic characteristics.
39. Hammer, Ann (2010). Forced use on arm function after stroke.
Clinically rated and self-reported outcome and measurement during
the sub-acute phase.
40. Westman, Anders (2010). Musculoskeletal pain in primary health
care: A biopsychosocial perspective for assessment and treatment.
41. Gustafsson, Sanna Aila (2010). The importance of being thin
Perceived expectations from self and others and the effect on
self-evaluation in girls with disordered eating.
42. Johansson, Bengt (2010). Long-term outcome research on PDR
brachytherapy with focus on breast, base of tongue and lip cancer.
43. Tina, Elisabet (2010). Biological markers in breast cancer and acute
leukaemia with focus on drug resistance.
44. Overmeer, Thomas (2010). Implementing psychosocial factors in
physical therapy treatment for patients with musculoskeletal pain
in primary care.
45. Prenkert, Malin (2010). On mechanisms of drug resistance in
acute myloid leukemia.
46. de Leon, Alex (2010). Effects of Anesthesia on Esophageal Sphincters
in Obese Patients.
47. Josefson, Anna (2010). Nickel allergy and hand eczema epidemiological
aspects.
48. Almon, Ricardo (2010). Lactase Persistence and Lactase Non-Persistence.
Prevalence, influence on body fat, body height, and relation to the metabolic
syndrome.
49. Ohlin, Andreas (2010). Aspects on early diagnosis of neonatal sepsis.
50. Oliynyk, Igor (2010). Advances in Pharmacological Treatment of Cystic
Fibrosis.
51. Franzn, Karin (2011). Interventions for Urinary Incontinence in Women.
Survey and effects on population and patient level.
52. Loiske, Karin (2011). Echocardiographic measurements of the heart. With
focus on the right ventricle.
53. Hellmark, Bengt (2011). Genotypic and phenotypic characterisation of
Staphylococcus epidermidis isolated from prosthetic joint infections.
54. Eriksson Crommert, Martin (2011). On the role of transversus abdominis
in trunk motor control.
55. Ahlstrand, Rebecca (2011). Effects of Anesthesia on Esophageal Sphincters.
56. Hollndare, Fredrik (2011). Managing Depression via the Internet
self-report measures, treatment & relapse prevention.
57. Johansson, Jessica (2011). Amino Acid Transport and Receptor Binding
Properties in Neuropsychiatric Disorders using the Fibroblast Cell Model.
58. Vidlund, Mrten (2011). Glutamate for Metabolic Intervention in Coronary
Surgery with special reference to the GLUTAMICS-trial.
59. Zakrisson, Ann-Britt (2011). Management of patients with Chronic
Obstructive Pulmonary Disease in Primary Health Care. A study of a
nurse-led multidisciplinary programme of pulmonary rehabilitation.
60. Lindgren, Rickard (2011). Aspects of anastomotic leakage, anorectal
function and defunctioning stoma in Low Anterior Resection of the
rectum for cancer.
61. Karlsson, Christina (2011). Biomarkers in non-small cell lung carcinoma.
Methodological aspects and influence of gender, histology and smoking
habits on estrogen receptor and epidermal growth factor family receptor
signalling.
62. Varelogianni, Georgia (2011). Chloride Transport and Inflammation in
Cystic Fibrosis Airways.
63. Makdoumi, Karim (2011). Ultraviolet Light A (UVA) Photoactivation of

Riboflavin as a Potential Therapy for Infectious Keratitis.
64. Nordin Olsson, Inger (2012). Rational drug treatment in the elderly: To
treat or not to treat.
65. Fadl, Helena (2012). Gestational diabetes mellitus in Sweden: screening,
outcomes, and consequences.
66. Essving, Per (2012). Local Infiltration Analgesia in Knee Arthroplasty.
67. Thuresson, Marie (2012). The Initial Phase of an Acute Coronary Syndrome.
Symptoms, patients response to symptoms and opportunity to reduce time to
seek care and to increase ambulance use.
68. Mrild, Karl (2012). Risk Factors and Associated Disorders of Celiac
Disease.
69. Fant, Federica (2012). Optimization of the Perioperative Anaesthetic Care
for Prostate Cancer Surgery. Clinical studies on Pain, Stress Response and
Immunomodulation.
70. Almroth, Henrik (2012). Atrial Fibrillation: Inflammatory and
pharmacological studies.
71. Elmabsout, Ali Ateia (2012). CYP26B1 as regulator of retinoic acid in
vascular cells and atherosclerotic lesions.
72. Stenberg, Reidun (2012). Dietary antibodies and gluten related seromarkers
in children and young adults with cerebral palsy.
73. Skeppner, Elisabeth (2012). Penile Carcinoma: From First Symptom to
Sexual Function and Life Satisfaction. Following Organ-Sparing Laser
Treatment.
74. Carlsson, Jessica (2012). Identification of miRNA expression profiles for
diagnosis and prognosis of prostate cancer.
75. Gustavsson, Anders (2012): Therapy in Inflammatory Bowel Disease.
76. Paulson Karlsson, Gunilla (2012): Anorexia nervosa treatment expectations,
outcome and satisfaction.
77. Larzon, Thomas (2012): Aspects of endovascular treatment of abdominal
aortic aneurysms.
78. Magnusson, Niklas (2012): Postoperative aspects of inguinal hernia surgery
pain and recurrences.
79. Khalili, Payam (2012): Risk factors for cardiovascular events and incident
hospital-treated diabetes in the population.
80. Gabrielson, Marike (2013): The mitochondrial protein SLC25A43 and its
possible role in HER2-positive breast cancer.
81. Falck, Eva (2013): Genomic and genetic alterations in endometrial

adenocarcinoma.
82. Svensson, Maria A (2013): Assessing the ERG rearrangement for clinical
use in patients with prostate cancer.
83. Lnn, Johanna (2013): The role of periodontitis and hepatocyte growth
factor in systemic inflammation.
84. Kumawat, Ashok Kumar (2013): Adaptive Immune Responses in the
Intestinal Mucosa of Microscopic Colitis Patients.
85. Nordenskjld, Axel (2013): Electroconvulsive therapy for depression.

Summary01 PDF

Загружено:

Сведения о документе

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

Summary01 PDF

Загружено:

Авторское право:

Доступные форматы

Electroconvulsive therapy for depression

Till min familj

rebro Studies in Medicine 85

Electroconvulsive therapy for depression

Axel Nordenskjld, 2013

II. Nordenskjld A, von Knorring L, Engstrm I. Predictors of time

III. Nordenskjld A, von Knorring L, Ljung T, Carlborg A, Brus O,

IV. Nordenskjld A, von Knorring L, Engstrm I. Rehospitalization

V. Nordenskjld A, von Knorring L, Brus O, Engstrm I. Predictors

Statistical analysis ................................................................................ 43

The cognitive subscale of the Alzheimer's Disease

Clinical Global Impression-Improvement

Diagnostic and Statistical manual of Mental disorders IV edition Text Revision

Hospital Day Quotient

International Classifications of Diseases 10th edition

Montgomery sberg Depression Rating Scale

Mini-International Neuropsychiatric Interview

MiniMental State Examination

National Institute for Clinical Excellence

Serotonin Nor-epinephrine Reuptake Inhibitor

Selective Serotonin Reuptake Inhibitor

Utvalg for Kliniske Undersgelser

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

AXEL NORDENSKJLD Electroconvulsive therapy for depression

Remission: A score of 10 or less on the Montgomery sberg Depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

sion. In animal studies, antidepressant treatments such as ECT result in

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

In the 1960s, Ottosson performed a series of experimental studies of ECT

Mode of action of ECT

AXEL NORDENSKJLD Electroconvulsive therapy for depression

associated with increased risks of complications. A treatment series usually

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

of amnesia by modifying the treatment technique according to the response.

Indications for ECT

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

Predictors of the short-term effectiveness of ECT

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

concluded that there were no long-lasting impairments in these functions

Common side effects and complications of ECT

AXEL NORDENSKJLD Electroconvulsive therapy for depression

Serious complications related to ECT

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

Relapse after ECT

Continuation ECT to prevent relapse after index ECT

AXEL NORDENSKJLD Electroconvulsive therapy for depression

Summary and scope for the empirical studies

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

to investigate the responder rate of ECT, in clinical routine

AXEL NORDENSKJLD Electroconvulsive therapy for depression

I AXEL NORDENSKJLD Electroconvulsive therapy for depression

AXEL NORDENSKJLD Electroconvulsive therapy for depression

Cohort study based