Co-occurring Addiction and

Less Severe
Mental Disorders

Richard Ries MD
rries@u.washington.edu
Harborview Medical Center
University of Washington
Seattle, Wa

DUAL DIAGNOSIS IS:

TWO DIAGNOSES/ DISORDERS

TWO SYSTEMS

DOUBLE TROUBLE

IN THE EYE OF THE BEHOLDER

Examples of Dual Disorders:

MENTAL DISORDERS
Schizophrenia
Bi-polar
Schizoaffective
Major Depression
Borderline
Personality
Post Traumatic
Stress
Social Phobia
others

ADDICTION
DISORDERS
Alcohol
Abuse/Depen.
Cocaine/ Amphet
Opiates
Marijuana
Polysubstance
combinations
Prescription drugs

Dual Disorders for

Everyone?

If applied to all cases, Term has no meaning

(eg Spider phobia and Running Addiction)

Both Mental and Addiction Disorders need to be

over threshold

Personality Disorders, other than Borderline not

usually counted

Substance Induced Disorders cause diagnostic

confusion

CHARACTERISTICS OF THE DUAL DIAGNOSIS

CLIENT IN KING COUNTY Ries 89
Severity of
Chemical Dependency
High
LH

HH
2

Severity of
Psychiatric
Condition

1
4

Low

HL

LL

Low

High

Systems Problems

Different Lawscommitment/confid.
Different funding..audits etc
Different personnel
Different training
Different certification
Different sites
Different Norms

The Four Quadrant Framework for

Co-Occurring Disorders
High
severity

Less severe
mental disorder/
more severe
substance
abuse disorder

Less severe
mental disorder/
less severe
substance
abuse disorder
Low
severity

A four-quadrant
conceptual framework
to guide systems
integration and
resource allocation in
treating individuals
with co-occurring
disorders
(NASMHPD,NASADAD,
1998; NY State; Ries,
1993; SAMHSA Report
to Congress, 2002)

More severe
mental disorder/
more severe
substance
abuse disorder

More severe
mental disorder/
less severe
substance
abuse disorder
High
severity

Not intended to be
used to classify
individuals (SAMHSA,
2002), but ...

DOUBLE TROUBLE
Hall
Alterman
Solomon
Safer
Drake
Barbee
Lyons
Chen

77
85
86
87
89
89
89
92

Poor out-pt attendance, discontinue Rx

More mood changes, intensive staffing
More noncompliance, arrests
Over twice hosp. rate and criminal behav
More hostility, noncompliance
More psych symptoms
More noncompliance, ER, jail, rehosp.
Worse treatment course

But what about NON- severely

mentally ill co-occurring pts?

Like in Addiction Treatment settings

Like in Criminal Justice settings

Like in Primary Care Settings

Like in ERs, especially with suicidal pts

The new TIP will bring more focus on

these populations

Likelihood of a Suicide Attempt

Increased Odds Of
Attempting
Suicide

Risk Factor

Cocaine use
Major Depression
Alcohol use
Separation or Divorce
NIMH/NIDA

62 times more likely

41 times more likely
8 times more likely
11 times more likely
ECA EVALUATION

Percent With Severe Suicide Rating

Double Trouble:
RELATIONSHIP OF ALCOHOL & DRUG PROBLEMS
TO SEVERE SUICIDALITY (n=12,196)

ODDS adjusted
for age & gender

ALCOHOL OR DRUG PROBLEMS

Walds = 235.41

p < .001

Ries & Russo

unpub , 2003

Drug Induced Psychopathology

Drug States

Withdrawal

Acute
Protracted

Symptom Groups

Intoxication
Chronic Use

Depression
Anxiety
Psychosis
Mania
Rounsaville 90

Twelve-Month Prevalence of DSM-IV Independent Mood and

Anxiety Disorders Among Respondents with DSM-IV
Substance Use Disorders Who Sought Treatment in the Past
12 Months

Disorder

Respondents, % (SE)

Those With Any Alcohol Use Disorder (5.81%)*

Any mood disorder
40.69 (4.11)
Major Depression
32.75 (4.01)
Dysthymia
11.01 (2.74)
Mania
12.56 (2.81)
Hypomania
3.07 (1.37)
Any anxiety disorder
33.38 (4.17)
Panic disorder
With agoraphobia
4.10 (1.54)
Without agoraphobia
9.10 (2.48)
Social phobia
8.49 (3.48)
Specific phobia
17.24 (3.10)
Generalized anxiety
12.35 (3.01)
disorder
Any drug use disorder
33.05 (4.23)
*Data in parentheses are the percentages of respondents with the substance use
Grant B, JAMA 2004
disorders who sought treatment in the past 12 months.

Twelve-Month Prevalence of DSM-IV Independent Mood and

Anxiety Disorders Among Respondents with DSM-IV
Substance Use Disorders Who Sought Treatment in the Past
12 Months

Disorder

Respondents, % (SE)

Those With Any Drug Use Disorder (13.10%)*

Any mood disorder
60.31 (5.86)
Major Depression
44.26 (6.28)
Dysthymia
25.91 (5.19)
Mania
20.39 (5.17)
Hypomania
2.48 (1.67)
Any anxiety disorder
42.63 (5.97)
Panic disorder
With agoraphobia
5.92 (2.19)
Without agoraphobia
8.64 (3.05)
Social phobia
12.09 (3.48)
Specific phobia
22.52 (4.99)
Generalized anxiety
22.07 (5.18)
disorder
Any alcohol use disorder
55.16 (6.29)
*Data in parentheses are the percentages of respondents with the substance use
Grant B, JAMA 2004
disorders who sought treatment in the past 12 months.

Comorbidity of
Depression and Anxiety
Disorders
50% to 65% of panic disorder
patients have depression

70% of social anxiety

disorder patients have
depression

67% of OCD
patients have
depression*

Panic
Disorder
HIGHLY
Depression COMMON Social
Anxiety
HIGHLY
Disorder
COMORBID
OCD

49% of social
anxiety disorder
patients have
panic disorder**

11% of social
anxiety disorder
patients have OCD**

Diagnostic Criteria for

Panic Attack
A discreet period of intense fear or discomfort
in which 4 or more of the following symptoms
developed abruptly and reached a peak within
10 minutes:
Palpitations, pounding
heart
Sweating
Trembling or shaking

Adapted with permission from American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed. 1994.

Diagnostic Criteria for

Panic Attack Continued

Dizziness
Chills or hot flushes
Feelings of unreality
Fear of losing
control or going
crazy
Fear of dying
Paresthesias

Choking feeling
Smothering or
shortness of breath
Chest pain or
discomfort
Abdominal distress

Somatic Symptoms In
Panic Disorder

Gastrointestinal
Symptoms

Chest Pain

SOMATIC
SYMPTOMS
Dizziness

Headache

Fatigue

Quality of Life in Panic Disorder

Marital Discord
(past 2 weeks)
Markowitz et al. Arch Gen Psychiatry. 1989;46:984.

Use Of ER
(past year)

Financial
Dependence
(welfare or
disability)

DSM-IV Diagnostic
Criteria for PTSD

Exposure to a traumatic event in which

the person:
experienced, witnessed, or was
confronted by death or serious injury to
self or others
AND
responded with intense fear,
helplessness,
or horror

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,

4th ed. 1994.

DSM-IV Diagnostic
Criteria for PTSD
Continued

Symptoms
appear in 3 symptom clusters: reexperiencing, avoidance/numbing,
hyperarousal
last for > 1 month
cause clinically significant distress or
impairment in functioning

DSM-IV Diagnostic Criteria

for PTSD Re-experiencing

Persistent re-experiencing of 1 of the following:

recurrent distressing recollections of event
recurrent distressing dreams of event
acting or feeling event was recurring
psychological distress at cues resembling event
physiological reactivity to cues resembling
event

DSM-IV Diagnostic Criteria for

PTSD Avoidance/Numbing

Avoidance of stimuli and numbing of general

responsiveness indicated by 3 of the following:
avoid thoughts, feelings, or conversations*
avoid activities, places, or people*
inability to recall part of trauma
interest in activities
estrangement from others
restricted range of affect
sense of foreshortened future

DSM-IV Diagnostic
Criteria for PTSD
Hyperarousal

Persistent symptoms of increased arousal 2:

difficulty sleeping
irritability or outbursts of anger
difficulty concentrating
hypervigilance
exaggerated startle response

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th
ed. 1994.

Prevalence of Trauma and

Probability of PTSD
1

Witness

Accident Threat w/
Weapon

Physical Molestation Combat

Attack
2

1
2

Rape

Impaired Quality of Life with

PTSD

SF-36
Score

SF-36 = 36 item short form health survey

Lower score = more impairment
Malik M et al. J Trauma Stress. 1999;12:387-393.

Complaints Of Social
Anxiety Disorder
Stuttering
Palpitations

Butterflies
Beidel. J Clin Psychiatry. 1998;59(suppl 17):27.

Blushing
Sweating
Trembling
And Shaking

Social Anxiety Disorder

SPIN Screener

Is being embarrassed or looking stupid

among your worst fears?
Does fear of embarrassment cause you to
avoid doing things or speaking to others?
Do you avoid activities in which you are the
center of attention?

Katzelnick et al. Presented at 37th Annual Meeting of the American College of

Neuropsychopharmacology; December 14-18, 1998; Los Croabas, Puerto Rico.

Social Anxiety Disorder: Educational

and Occupational Impairment
0.0

-5.0
Impairment**
(%)
-10.0
Wages
-15.0

-20.0

College
Graduation
Professional
Or
Management Positions

* LSAS score in controls = 25; ** Impairment (%) refers to percentage change in wages and percentage
point changes in probabilities of college graduation and having a technical, professional, or
managerial job.
Katzelnick et al. Presented at 37th Annual Meeting of the American College of Neuropsychopharmacology;
December 14-18, 1998; Los Croabas, Puerto Rico.

Therapy Plan
Bio

Psych

Social

Psych

Labs
Meds (anti-depressants,
etc.)
psychotherapy
education groups
process groups
Couples conf.
D/C planning
housing, etc.

CD

Labs
Meds (withdrawal, craving,
etc.)
Step work
Groups
AA Meetings
Intervention
Sober housing

1: JAMA. 2004 Apr 21;291(15):188796.

Related Articles, Links

Treatment of depression in patients with alcohol or other drug

dependence: a meta-analysis.
Nunes EV, Levin FR.

DATA SYNTHESIS: For the HDS score, the pooled effect size from the random-effects model was
0.38 (95% confidence interval, 0.18-0.58). Heterogeneity of effect on HDS across studies was
significant (P <.02), and studies with low placebo response showed larger effects.
Moderator analysis suggested that diagnostic methods and concurrent psychosocial interventions
influenced outcome.
Studies with larger depression effect sizes (>0.5) demonstrated favorable effects of medication on
measures of quantity of substance use, but rates of sustained abstinence were low.
CONCLUSIONS: Antidepressant medication exerts a modest beneficial effect for

patients with combined depressive- and substance-use disorders. It is not a

stand-alone treatment, and concurrent therapy directly targeting the addiction is
also indicated.
More research is needed to understand variations in the strength of the effect, but the data suggest
that care be exercised in the diagnosis of depression-either by observing depression to persist
during at least a brief period of abstinence or through efforts by clinical history to screen out
substance-related depressive symptoms.

: Psychopharmacol Bull.
1998;34(1):117-21.

Related Articles, Links

Fluoxetine versus placebo in depressed alcoholic cocaine abusers.

Cornelius JR, Salloum IM, Thase ME, Haskett RF, Daley DC, Jones-Barlock A, Upsher C, Perel JM .

All 51 patients participated in a double-blind, parallel group study of fluoxetine versus placebo in depressed
alcoholics. The principal focus of this article is the one-third of the depressed alcoholics who also abused cocaine
and how the treatment response of those 17 patients compared with that of the 34 depressed alcoholics who did
not abuse cocaine.
During the study, no significant difference in treatment outcome was noted between the fluoxetine group
(N = 8) and the placebo group (N = 9) for cocaine use, alcohol use, or depressive symptoms. In addition,
no significant within-group improvement was noted for any of these outcome variables in either of the two
treatment groups.
Indeed, across the combined sample of 17 depressed alcoholic cocaine abusers, the mean Beck Depression
Inventory (BDI) score worsened slightly from 19 to 21 during the course of the study, and 71 percent of the
patients continued to complain of suicidal ideations at the end of the study.
The 17 cocaine-abusing depressed alcoholics showed a significantly worse outcome than the 34 non-cocaine
abusing depressed alcoholics on the 24-item Hamilton Rating Scale for Depression (HAM-D) and BDI depression
scales and on multiple measures of alcohol consumption. These findings suggest that comorbid cocaine
abuse acts as a robust predictor of poor outcome for the drinking and the depressive symptoms of
depressed alcoholics.

Depress Anxiety.
2001;14(4):255-62.

Related Articles, Links

Paroxetine for social anxiety and alcohol use in dual-diagnosed patients .

Randall CL, Johnson MR, Thevos AK, Sonne SC, Thomas SE, Willard SL, Brady KT, Davidson JR.

Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol use
disorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in a
double-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/d
and increased to a target dose of 60 mg/d.
There was a significant effect of treatment group on social anxiety symptoms, where patients
treated with paroxetine improved more than those treated with placebo on both the
Clinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05).
On alcohol use, there was not a significant effect of treatment on quantity/frequency measures
of drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebo
patients were improvers on drinking, P < or = 0.05).
This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder in
individuals with comorbid alcohol problems, and positive treatment effects can be seen in as
little as 8 weeks. Further study is warranted to investigate its utility in helping affected
individuals reduce alcohol use. Copyright 2001 Wiley-Liss, Inc.

Why arent Antidepressants more

effective in addictions patients?

Psychiatric outcomes:
Antidepressants only beat placebo by 20% anyway in
NON addicts
Study patients also get addiction rx
Maybe addiction rx is more anti-dep, anti anx than we
thinkviz Schuckit 80% -> 20%
This is poorly studiedmaybe better with 12 step
Sub Induced criteria are wrong
Addictions outcomes
Meds take focus off sobriety
Meds reinforce sobriety
Just dont work for this

Alcohol Clin Exp Res. 2001 Feb;25(2):21020.

Concurrent alcoholism and social anxiety disorder: a first step toward

developing effective treatments.
Randall CL, Thomas S, Thevos AK.

The present study investigated whether simultaneous treatment of social phobia and alcoholism, compared
with treatment of alcoholism alone, improved alcohol use and social anxiety for clients with dual diagnoses
of social anxiety disorder and alcohol dependence.
METHODS: The design was a two-group, randomized clinical trial that used 12 weeks of individual
cognitive behavioral therapy for alcoholism only (n = 44) or concurrent treatment for both alcohol and social
anxiety problems (n = 49). Outcome data were collected at the end of 12 weeks of treatment and at 3
months after the end of treatment.
RESULTS: Results with intent-to-treat analyses showed that both groups improved on alcohol-related
outcomes and social anxiety after treatment.

Counter to the hypothesis, the group treated for both alcohol and social anxiety
problems had worse outcomes on three of the four alcohol use indices.
No treatment group effects were observed on social anxiety indices.
CONCLUSIONS: Implications for the staging of treatments for coexisting social phobia and alcoholism are
discussed, as well as ways that modality of treatments might impact outcomes.

J Subst Abuse Treat. 2003

Sep;25(2):99-105.

Related Articles, Links

A cognitive-behavioral treatment for incarcerated women with

substance abuse disorder and posttraumatic stress disorder: findings
from a pilot study.
Zlotnick C, Najavits LM, Rohsenow DJ, Johnson DM.

This preliminary study evaluates the initial efficacy of a cognitive-behavioral treatment,

Seeking Safety, as an adjunct to treatment-as-usual in an uncontrolled pilot study of
incarcerated women with current SUD and comorbid PTSD.
Of the 17 incarcerated women with PTSD and SUD who received Seeking Safety treatment
and had outcome data,
results show that nine (53%) no longer met criteria for PTSD at the end of

treatment; at a followup 3 months later, seven (46%) still no longer met criteria
for PTSD
Additionally, there was a significant decrease in PTSD symptoms from intake to posttreatment,
which was maintained at the 3-month followup assessment.
Based on results from a diagnostic interview and results of urinalyses, six (35%) of the
women reported the use of illegal substances within 3 months from release from prison.
Measures of client satisfaction with treatment were high. Recidivism rate (return to prison) was
33% at a 3-month followup.

Can encouraging substance abuse patients to

participate in self-help groups reduce demand for
health care?
A quasi-experimental study
n=1774, 1 year follow-up

Outpt
Visits

Humphreys et al ..2001

Inpt days

Abstinence
Rates

12 Step

13.1

10.5

45.7

Cog Beh

17

17

36.2

* all p< .001

** 64% higher cost for CBT

Dual Screening:

the Dual Cage.easy, but no data

ASAM pt placement..needs experience, little or no
data
ASI psych.short, available, good screening,
good data
Beck, Zung, Ham D etc..easy, good data, may be limited
Brief Symptom Inventoryeasy, broad symptom mix
Otherssee new Co-occurring TIP in 1204

Dual CAGE QUESTIONS

Cut Down (or stopped)

Annoyed when drug/alc. use discussed

Because mental symptoms worsened

Because MH doctor or therapist suggested
Annoyed, anxious or angry, fights when using
Admitted to ER or hospital for psych when using or not
ADHD when child

Guilty about use

Guilty, depressed, suicidal when using or not

Ever made a suicide attempt when using or not

CAGE Questions

Eye opener: taken drink or drug in AM to feel

better
Taken a drink or drug to blot out symptoms
Taken drink or drug with psych med
Not taken meds because of using drug/alc
(forgot, avoid mixing, etc.)

What are 2 or 3 reasons you use alc/drugs?

What are 2 or 3 reasons you might want to
stop or cut down?

Medications

Essential to Treatment of Severely

Mentally Ill

Substance Use and Not-Taking Meds are the 2

top reasons for De-Comp
Should be part of court orders
Monitored by Case managers, nurses, doctors

For Dep/Anx, less clear

Personal experience shows maximizing 12 step

AND use of meds is best rx

It may not be that the med(s)

stopped working, but

The patient stopped the med

The patient stopped the med AND used
drugs and/or alcohol...
OR lowered the med and used
OR used on top of the med.
OR used twice the dose on one day and
nothing the next.
Stimulants ( cocaine/amphets) are most
MSE destructive.

How to use AA as a treatment

partner

1. Know something about AA, its history,

presence in your community, structure and
content

2. Helpful Readings:

Brown: A psychological view of the 12 steps

AA: AA for the medical practitioner; and
The AA member and medications
Twelve Step Facilitation Therapy Manual

Project Match, NIAAA web site

Forman: One AA Meting doesnt fit all

One year ABSTINENCE was predicted by:

AA involvement (OR=2.9), ( n=377)

not having pro-drinking influences in one's network (OR=0.7

having support for reducing consumption from people met

in AA (versus no support; OR=3.4).
In contrast, having support from non-AA members was
not a significant predictor of abstinence.
Kaskutas: Addiction 2002

Double Trouble Recovery (DTR)

Outcomes

Members of 24 DTR groups (n=240) New York City,

1 year outcomes

Drug/alcohol abstinence = 54% at baseline,

increased to 72% at follow-up.

More attendance = better Medication adherence,

Better Medication adherence = less hospitalization

Magura Add Beh 2003, Psych Serv 2002

Dual Dep/Anx RX plan

Differential Dx
12 step facilitation
Meds if indicated ( and I often use them)
Visits:

Ries 1/week ( 12 step facil and meds)

AA 3x week or 90 in 90
Meet with sponsor
Meet with family

Low mental illness/High addictions outpt

gets

In most MHCs:

MD visit q 3 months
CM visit q 2 wksfocus on ADLs
Maybe dual dx group 1-2 hrs/wk
Limited expectations of recovery
Pschotherapy time ~ 0-2 hrs week

In the most Addictions IOPs

MD visit 1/ 3 months, often 1 care

CM 1:1 q 2 wks.focus on Sub use, U toxs
IOP group 3 hrs-3x week
Expectations of Sobriety/progress
Psychotherapy time 3-10 hrs week ( plus more AA)

Report Questions Ability of National Treatment Infrastructure to Deliver Quality Care

100%
80%
Percentage
of Programs 60%

54%

40%
25%
20%

15%

20%

0%
Closed or Stopped
Services

Reorganized

Director in
No Information
Position Less Than Services, E-mail,
One Year
or Voicemail

SOURCE: Adapted by CESAR from the McLellan, A. T., Carise, D., and Kleber, J., Can the National Addiction Treatment Infrastructure Support the Publics
Demand for Quality Care? Journal of Substance Abuse Treatment 25(2):117-121, 2003. For more information, contact Dr. A. Thomas McLellan at
tmclellan@tresearch.org.

301-405-9770 (voice) 301-403-8342 (fax) CESAR@cesar.umd.edu www.cesar.umd.edu

CESAR FAX is supported by VOIT 1996-1002, awarded by the U.S. Department of Justice through the Governors Office of Crime Control and Prevention. CESAR

New Issues in Medications for

Co-occurring Addiction and
Mental Disorders
Richard Ries MD

Medication monitoring and

motivating

Know who is on what and what for

Know the prescriber if possible

Sit in on med sessions onsite
Talk to off-site doctor or nurse PRE problem!!!

Know something about meds

ATTC Tech transfer centers summary
New COD TIP ( Dec 04)
NIMH web site, NAMI web site

Medications: counselors
role

Ask the pt about :

Compliance

Effectiveness

sometimes people forget their medicationshow often does this

happen to you? ie % not taking
how well do you think the meds are working?
what do you notice
here is what I notice

Side Effects.

are you having any side effects to the medication?

what are they
have you told the prescriber?
do you need help with talking to the presciber?

Medications.potential
problems

Can reinforce addiction denial if recovery is not

integrated and supportedesp by the
prescriber..( so work with them)
Can be expensive, cause side effects, could be
used in overdose.
Encumber the pt with seeing MD, or mental
health system, cost, convenience etc.ie make
sure they are really necessary.
Active participation in recovery can be both
antidep and antianxbut if these problems
continue, or disrupt recovery, meds should be
considered

Antipsychotics

Alcohol Clin Exp Res. 2004

May;28(5):736-45.

A double-blind, placebo-controlled study of olanzapine in the

treatment of alcohol-dependence disorder.
Guardia J, Segura L, Gonzalvo B, Iglesias L, Roncero C, Cardus M, Casas M.

METHODS: A total of 60 alcohol-dependent patients were assigned to 12 weeks' treatment

with either olanzapine or placebo. The primary variable relapse to heavy drinking rate was
evaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverse
events, and changes in the biochemical markers of heavy drinking and possible toxicity were
also evaluated.
RESULTS: We did not find significant differences in the survival analysis between placebo and
olanzapine-treated patients (Kaplan-Meier log rank = 0.46, df = 1, p = 0.50). Eleven (37.9%)
patients treated with olanzapine relapsed compared with 9 (29%) of those receiving placebo
(chi = 0.53, df = 1, p = 0.5). Although some adverse events (weight gain, increased appetite,
drowsiness, constipation, and dry mouth) were found more frequently in the olanzapine group,
differences did not reach statistical significance in comparison with the placebo group.
CONCLUSIONS: We found no differences in relapse rate or other drinking variables
when comparing olanzapine with placebo-treated patients.

J Clin Psychopharmacol. 2000

Feb;20(1):94-8.

Effects of clozapine on substance use in patients with schizophrenia

and schizoaffective disorder: a retrospective survey.
Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI .

. The authors report data from a retrospective survey of substance use in 58

patients treated with clozapine who had a history of comorbid schizophrenia (or
schizoaffective disorder) and substance use disorder. Of these 58 patients, 43 were
being treated with clozapine at the time of the survey; the remaining 15 patients had
discontinued clozapine before the survey.
More than 85% of the patients who were active substance users at the time of
initiation of treatment with clozapine decreased their substance use over the
course of clozapine administration. For patients who continued treatment with
clozapine up to the present, the decrease in substance use was strongly correlated
with a decrease in global clinical symptoms.

Schizophr Res. 2004 Feb 1;66(2-3):125-35.

First episode schizophrenia-related psychosis and substance use disorders:
acute response to olanzapine and haloperidol.
Green AI, Tohen MF, Hamer RM, Strakowski SM, Lieberman JA, Glick I, Clark WS; HGDH Research Group.

METHODS: The study involved 262 patients. Patients with a history of substance
dependence within 1 month prior to entry were excluded.
RESULTS: Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder
(SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) had
a lifetime diagnosis of alcohol use disorder (AUD).
Those with CUD had a lower age of onset than those without.
Patients with SUD were more likely to be men.
Patients with SUD had more positive symptoms and fewer negative symptoms than
those without SUD, and they had a longer duration of untreated psychosis.
The 12-week response data indicated that 27% of patients with SUD were responders
compared to 35% of those without SUD.
Patients with AUD were less likely to respond to olanzapine than those without AUD.
DISCUSSION: These data suggest that first-episode patients are quite likely to have comorbid
substance use disorders, and that the presence of these disorders may negatively influence
response to antipsychotic medications, both typical and atypical antipsychotics, over the first 12
weeks of treatment.

Bipolar Disord. 2002

Dec;4(6):406-11.

Related Articles, Links

Quetiapine in bipolar disorder and cocaine dependence.

Brown ES, Nejtek VA, Perantie DC, Bobadilla L.

METHODS: Open-label, add-on, quetiapine therapy was examined for 12 weeks in 17

outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated with a
structured clinical interview; Hamilton Depression Rating (HDRS), Young Mania Rating
(YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving Questionnaire (CCQ).
Urine samples and self-reported drug use were also obtained. Data were analyzed using a last
observation carried forward method on all subjects given medication at baseline.
RESULTS:
Significant improvement from baseline to exit was observed in HDRS, YMRS, BPRS and
CCQ scores (p < or = 0.05).
Dollars spent on cocaine and days/week of cocaine use decreased non-significantly,
and urine drug screens did not change significantly from baseline to exit.
Quetiapine was well tolerated, with no subjects to our knowledge discontinuing because of
side-effects. CONCLUSIONS: The use of quetiapine was associated with substantial
improvement in psychiatric symptoms and cocaine cravings. The findings are promising and
suggest larger controlled trials of quetiapine are needed in this population.

Schizophr Res. 2003 Mar

1;60(1):81-5.

Alcohol and cannabis use in schizophrenia: effects of clozapine vs.

risperidone.
Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD.

METHOD: This study involved retrospective assessment of abstinence

(cessation of alcohol and cannabis use) in 41 patients treated with either
risperidone (n=8) or clozapine (n=33) for at least 1 year. In 32 of these 41
patients, information was available on whether abstinence occurred during
the 1-year period.
RESULTS: Abstinence rates were significantly higher in patients
treated with clozapine than in those treated with risperidone (54% vs.
13%, p=0.05).

Eur J Pharmacol.
2003 May
9;468(2):121-7.

Risperidone reduces limited access alcohol drinking in alcoholpreferring rats.

Ingman K, Honkanen A, Hyytia P, Huttunen MO, Korpi ER.

Department of Pharmacology and Clinical Pharmacology, University of Turku,

Itainen Pitkakatu 4, FIN-20520, Turku, Finland
An atypical antipsychotic drug risperidone reduced ethanol drinking of
ethanol-preferring Alko, Alcohol (AA) rats in a limited access paradigm. Its
effect was transient at a dose known to preferentially antagonize the 5-HT(2)
receptors (0.1 mg/kg, s.c.), but long-lasting when the dose was increased to 1.0
mg/kg that also blocks dopamine D(2) receptors.

Can J Psychiatry. 2002

Sep;47(7):671-5.

Related Articles, Links

Risperidone decreases craving and relapses in individuals with

schizophrenia and cocaine dependence.
Smelson DA, Losonczy MF, Davis CW, Kaune M, Williams J, Ziedonis D.

OBJECTIVE: To examine the efficacy of atypical neuroleptics for decreasing craving and drug relapses
during protracted withdrawal in individuals dually diagnosed with schizophrenia and cocaine dependence.
METHOD: We conducted a 6-week, open-label pilot study comparing risperidone with typical neuroleptics
in a sample of withdrawn cocaine-dependent schizophrenia patients.
RESULTS: Preliminary results suggest that individuals treated with risperidone had significantly
less cue-elicited craving and substance abuse relapses at study completion. Further, they showed a
trend toward a greater reduction in negative and global symptoms of schizophrenia.
CONCLUSION: Atypical neuroleptics may help reduce craving and relapses in this population. Future
research should include more rigorous double-blind placebo-controlled studies with this class of
medications.

Comorbid Substance Abuse Associated

With Noncompliance in Schizophrenia

Nearly half of all patients in

a prospective 4-year study
(N = 99) were active
substance abusers (n =
42)
Patients who actively
abused substances were
significantly more likely to
be noncompliant

% Noncompliant

P < 0.05

Hunt GE et al. Schizophrenia Res. 2002;54:253-264.

It may not be that the

med(s) stopped working,
The patient but
stopped the med

The patient stopped the med AND used

drugs and/or alcohol...
OR lowered the med and used
OR used on top of the med.
OR used twice the dose on one day and
nothing the next.
Stimulants ( cocaine/amphets) are most
MSE destructive.

RISPERDAL CONSTA
Injection Kit Components
Needle Pro Device
SmartSite
Access
Device

Aqueous
Diluent

Risperidone
Microspheres

Assembled
RISPERDAL CONSTA

PRC approved with

PRC approved with
changes:
changes:11/10/03
11/10/03
(RISPERDAL
(RISPERDALCONSTA
CONSTA
Promotional
slide
Promotional slidekit)
kit)

Safety Needle

Risperidone +
9-hydroxyrisperidone (ng/mL)

Blood Levels Over Time

After Single Dose*
PRC
PRCapproved
approvedwith
with
changes:
11/10/03
changes: 11/10/03
(RISPERDAL
(RISPERDALCONSTA
CONSTA
Promotional
Promotionalslide
slidekit)
kit)

Antipsychotic
Supplementation

6
Time (wk)

*25-mg dose, N = 14.

Data on file, Janssen Pharmaceutica Products, L.P.

10

11

12

Substance Induced Psychoses

Amphet/Methamphetamines
Cocaine
Ecstacy
Hallucinogens ( strong THC too)
Other Rave Drugs
Alcohol WD and Hallucinosis

Anticonvulsants

COMPARING THE KNOWN EFFICACY OF

ANTIEPILEPTIC AGENTS IN BIPOLAR DISORDER
Drug

Mania

Depression

Maintenance

Comments

New Depakote ER
Formulation

2 new maintenance studies

v. lithium

Gabapentin

2 negative placebocontrolled studies in mania

Lamotrigine

Antidepressant activity in
several controlled trials

Topiramate

Dose-related weight loss

Valproate
Carbamzepine

Key:

Efficacy demonstrated in > 2 placebo-controlled trials

Efficacy demonstrated in one placebo-controlled or two large, active

comparator trials
Efficacy in two small or one large active comparator trial
Efficacy only in open trials and case series
Conflicting evidence of efficacy in available studies
Lack of efficacy demonstrated in randomized, controlled trials
ND No data presently available
Keck & McElroy, 2002

COMPARING THE KNOWN EFFICACY OF

ANTIEPILEPTIC AGENTS IN BIPOLAR DISORDER
Drug

Mania

Depression

Maintenance

Comments

Improved tolerability &

pharmacokinetics

Zonisamide

ND

ND

May produce weight loss

in some patients

Tiagabine

ND

ND

More data needed

regarding tolerability and
efficacy

Levetiracetam

ND

ND

ND

Data needed regarding

efficacy and tolerability

Oxcarbazepine

Key:

ND

Efficacy in two small or one large active comparator trial

Efficacy only in open trials and case series
Conflicting evidence of efficacy in available studies
No data presently available
Keck & McElroy, 2002

Eur Neuropsychopharmacol. 2004

Aug;14(4):319-23.

Related Articles, Links

How real are patients in placebo-controlled studies of acute manic episode?

Storosum JG, Fouwels A, Gispen-de Wied CC, Wohlfarth T, van Zwieten BJ, van den Brink W.

OBJECTIVE: To determine whether the results from placebo-controlled studies conducted in

patients with manic episode can be generalised to a routine population of hospitalised acute
manic patients.
METHODS: A list of four most prevalent inclusion and the nine most prevalent exclusion
criteria was constructed for participation in previous randomised-controlled trials (RCTs). On
the basis of this list, a consecutive series of 68 patients with 74 episodes of acute mania who
had been referred for routine treatment were retrospectively assessed to determine their
eligibility for a hypothetical but representative randomised controlled trial.
RESULTS: Only 16% of the manic episodes would qualify for the hypothetical trial (male
episodes 28%, female episodes 10%),
.whereas 37%, 20% and 27% of the manic episodes would have to be excluded because
they did no fulfil one, two or at least three of the inclusion or exclusion criteria. CONCLUSION:
Only a small percentage acute manic episodes in a routine mental hospital seem to
qualify for a standard placebo-controlled RCT.. These notions should be taken into account
when evaluating the results of RCTs in bipolar patients with an acute manic episode.

Am J Addict 2002
Spring;11(2):141-50

The differential effects of medication on mood, sleep disturbance, and

work ability in outpatient alcohol detoxification.
Malcolm R, Myrick H, Roberts J, Wang W, Anton RF.

A double-blind, randomized controlled trial of patients (n = 136) meeting DSM-IV

criteria for alcohol withdrawal and stratified based on detoxification history were
treated with carbamazepine or lorazepam for 5 days on a fixed dose tapering
schedule. Mood symptoms improved for all subjects regardless of medication or
detoxification history.
main effect favoring carbamazepine in reducing anxiety (p = 0.0007).
main effect of medication on sleep that again favored carbamazepine (p =
0.0186).
In this study of outpatients with mild to moderate alcohol withdrawal,
carbamazepine was superior to lorazepam in reducing anxiety and improving sleep.

Alcohol Clin Exp Res 2001

Sep;25(9):1324-9

Related Articles, Books, LinkOut

Divalproex sodium in alcohol withdrawal: a randomized

double-blind placebo-controlled clinical trial.
Reoux JP, Saxon AJ, Malte CA, Baer JS, Sloan KL.
Veterans Affairs Puget Sound Health Care System and
Department of Psychiatry, University of Washington School of
Medicine, Seattle, Washington 98108, USA.
joe.reoux@med.va.gov

Psychiatr Serv. 2000 May;51(5):634-8.

Related Articles, Links

Changes in use of valproate and other mood stabilizers for patients

with schizophrenia from 1994 to 1998.
Citrome L, Levine J, Allingham B.

METHODS: For each calendar year from 1994 through 1998, data were drawn from
a database containing clinical and drug prescription information for every inpatient in
the adult civil facilities of the New York State Office of Mental Health.
RESULTS: In 1994 a total of 26.2 percent of inpatients diagnosed as having
schizophrenia received a mood stabilizer, compared with 43.4 percent in 1998. In
1994 lithium was the most commonly prescribed mood stabilizer, for 13.2 percent of
patients, followed by valproate, for 12.3 percent. In 1998 valproate was the most
commonly prescribed, for 35 percent of patients, followed by lithium, for 11.3
percent. On average, patients received valproate for about two-thirds of their
hospital stay, at a mean dose of 1,520 mg per day.
CONCLUSIONS: The adjunctive use of valproate nearly tripled from 1994 to
1998 among patients with a diagnosis of schizophrenia. Valproate has become
the most commonly prescribed mood stabilizer for this population, despite the
paucity of evidence in the literature for efficacy in this use. Controlled clinical trials
are needed to examine the adjunctive use of mood stabilizers, in particular
valproate, among patients with schizophrenia.

Psychiatr Serv. 2004 Mar;55(3):290-4.

Related Articles, Links

Adjunctive divalproex and hostility among patients with

schizophrenia receiving olanzapine or risperidone.
Citrome L, Casey DE, Daniel DG, Wozniak P, Kochan LD, Tracy KA.

METHODS: A total of 249 inpatients with schizophrenia were randomly assigned,

RESULTS: Combination treatment with risperidone or olanzapine plus divalproex
was associated with different scores on the hostility item of the PANSS compared
with antipsychotic monotherapy.
This result was not seen beyond the first week of treatment, but there was a
trend toward a difference in effect for the entire treatment period.
Combination therapy had a significantly greater antihostility effect at days 3
and 7 than monotherapy.
The effect on hostility appears to be statistically independent of
antipsychotic effect on other PANSS items reflecting delusional thinking,
a formal thought disorder, or hallucinations.
CONCLUSIONS: Divalproex sodium may be useful as an adjunctive agent in
specifically reducing hostility in the first week of treatment with risperidone or
olanzapine among patients with schizophrenia experiencing an acute psychotic
episode.

J Clin Psychopharmacol. 2001

Feb;21(1):21-6.

Related Articles, Links

Divalproex sodium augmentation of haloperidol in hospitalized

patients with schizophrenia: clinical and economic implications.
Wassef AA, Hafiz NG, Hampton D, Molloy M.

Divalproex sodium has been approved for use in treating bipolar disorder. Its
usefulness in schizophrenia has yet to be adequately assessed.
Compared with those who received no or delayed augmentation, the earlyaugmentation group required 44.8% fewer inpatient days from the initiation of
haloperidol treatment. Patient response to treatment was particularly noted in
suspiciousness, hallucinations, unusual thought content, and emotional withdrawal.
Early augmentation with valproate may reduce the length of inpatient stays
and provide substantially better therapeutic outcomes. It is, however,
premature to recommend changes in the standard clinical management of
schizophrenia on the basis of the data provided herein, in view of the small sample
and open-label nature of the report.

Depakote with Atypical Antipsychotic: lipids

Patients treated with a combination of Depakote and Zyprexa experienced a
minimal increase in total cholesterol compared to the greater increase in
patients treated with Zyprexa when used as monotherapy:
+26.62 mg/dL for Zyprexa monotherapy (baseline: 193 mg/dL).
+0.87 mg/dL for Depakote plus Zyprexa (baseline: 198 mg/dL).
Patients treated with a combination of Depakote and Risperdal experienced a
decrease in total cholesterol compared to Risperdal when used as
monotherapy:
+9.64 mg/dL for Risperdal monotherapy (baseline: 188 mg/dL).
-13.44 mg/dL for Depakote plus Risperdal (baseline: 192 mg/dL).
Patients in the Zyprexa monotherapy group had the highest rate of shift from a
normal total cholesterol (<200 mg/dL) to a high total cholesterol (>200 mg/dL).
Casey et al APA conv 2004

Lancet. 2003 May 17;361(9370):1677-85.

Oral topiramate for treatment of alcohol dependence: a

randomised controlled trial. Johnson BA et al
METHODS: double-blind randomised controlled 12-week clinical trial
comparing oral topiramate and placebo for treatment of 150 individuals with
alcohol dependence..
FINDINGS: At study end, participants on topiramate, compared with
those on placebo, had

2.88 (95% CI -4.50 to -1.27) fewer drinks per day (p=0.0006),

3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009),
27.6% fewer heavy drinking days (p=0.0003),
26.2% more days abstinent (p=0.0003), and a
log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to 0.02) less (p=0.0046).

Topiramate-induced differences in craving were also significantly greater than

those of placebo, of similar magnitude to the self-reported drinking changes,
and highly correlated with them.

Topiramate for Alcohol Withdrawal:

1: Med Arh. 2002;56(4):211-2.
A pilot study of Topiramate (Topamax) in the treatment of tonic-clonic seizures
of alcohol withdrawal syndromes. Rustembegovic A, Sofic E, Kroyer G. Anton
Proksch Institute, Vienna, Austria.
12 patients with median age of 49.5 years and median body weight of
76.3 kg were treated with topiramate twice daily for up 30 days, starting with a
dose of 50 mg in the morning and 50 mg in the evening.
The preliminary findings of this study suggest that topiramate is
very effective against tonic-clonic seizures in alcohol withdrawal
syndrome. No side effects were observed. Only two patients had loss of body
weight (3-3.5 kg/4 weeks).

J Clin Psychopharmacol. 2004 Aug;24(4):374-8. Vieta E,et al

Effects on weight and outcome of long-term olanzapinetopiramate combination treatment in bipolar disorder .
Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for
treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n =
1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being
euthymic. Thirteen (50%) patients completed the 1-year follow-up.
By intent-to-treat, patients significantly improved from baseline in

Young Mania Rating Scale scores (P < 0.0001),

Hamilton Depression Rating Scale (P < 0.05), and
Modified Clinical Global Impressions for Bip (mania P < 0.0001,
Depression ( Ham) P < 0.05, overall P < 0.0001).

Most patients gained weight during the first month of combined treatment (mean
weight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight change
was -0.5 +/- 1.1 kg.

Subst Abus. 2003 Jun;24(2):29-32.

Gabapentin for the treatment of ethanol withdrawal.

Voris J, Smith NL, Rao SM, Thorne DL, Flowers QJ.
We retrospectively report on the use of gabapentin for ethanol withdrawal in 49
patients. Thirty-one patients were treated in the outpatient program and 18 in the
general inpatient psychiatric unit.
Positive outcomes as evidenced by completion of gabapentin therapy were
achieved in 25 out of 31 outpatients and 17 out of 18 inpatients.
Statistical significance was reached regarding the positive relationship between prior
ethanol use and inpatient "as needed" benzodiazepine use. Both sets of data
suggest that gabapentin works well for the mild to moderate alcohol withdrawal
patient.

Psychiatry Clin Neurosci. 2003

Oct;57(5):542-4.

Related Articles, Links

Open pilot study of gabapentin versus trazodone to treat insomnia in

alcoholic outpatients.
Karam-Hage M, Brower KJ.

Alcohol-dependent outpatients with persisting insomnia were treated with either gabapentin or
trazodone. Patients were assessed at baseline and after 4-6 weeks on medication using the
Sleep Problems Questionnaire (SPQ). Of 55 cases initially treated, 9% dropped out due to
morning drowsiness. Of the remaining 50 cases, 34 were treated with gabapentin (mean dose
+/- SD = 888 +/- 418 mg) at bedtime and 16 were treated with trazodone (105 +/- 57 mg) at
bedtime.
Both groups improved significantly on the SPQ but the gabapentin group improved
significantly more than the trazodone group. Controlled studies are warranted to
replicate these findings.

Med Arh. 2004;58(1):5-6.

A study of gabapentin in the treatment of tonic-clonic

seizures of alcohol withdrawal syndrome.
Rustembegovic A, Sofic E, Tahirovic I, Kundurovic Z.

In this study for thirty (30) patients with alcohol withdrawal syndrome, the
response to anticolvusant gabapentin was assessed. Thirty (30) patients
with median age of 57.0 years and median body weight of 79.1 kg were
treated with gabapentin 3 x 300 mg daily for up 30 days.
The preliminary findings of this study suggest that gabapentin is very
effective against tonic-clonic seizures in alcohol withdrawal
syndrome.
Gabapentin was safe and well tolerated. For twenty (20) patients no side
effect were observed.

J Clin Psychiatry. 2003 Feb;64(2):197201.

Related Articles, Links

Lamotrigine in patients with bipolar disorder and cocaine dependence.

Brown ES, Nejtek VA, Perantie DC, Orsulak PJ, Bobadilla L.

METHOD: Lamotrigine was started at a dose of 25 mg/day (12.5 mg/day in those taking
valproic acid) and titrated to a maximum dose of 300 mg/day. The subjects consisted of 13
men and 17 women with cocaine dependence and bipolar I disorder (N = 22), bipolar II
disorder (N = 7), or bipolar disorder not otherwise specified (N = 1), with a mean +/- SD age of
35.4 +/- 7.2 years. Data were analyzed using the last observation carried forward on all
subjects who completed the baseline evaluation and at least 1 postbaseline assessment.
RESULTS: Significant improvement was observed in HAM-D, YMRS, and BPRS scores
(p < or =.02). Cravings also significantly decreased as measured by the CCQ (p <.001).
Dollar amount spent on drugs decreased nonsignificantly. Lamotrigine was well
tolerated, with no subjects discontinuing due to side effects.
CONCLUSION: Lamotrigine treatment was well tolerated in this sample and associated with
statistically significant improvement in mood and drug cravings but not drug use. The findings
suggest that larger controlled trials of lamotrigine are needed in this population.

Anti-opiate Addiction Meds

Harm reduction:..opiates

Methadone

LAAM.

Not given orally

Suboxone

Due to liver prolems ( minor) is being phased out

Buprenorphine

Only through Methadone agencies for Addiction

Confusion when injury/pain/addiction co-occurr

Combination of Bup plus Naloxone subligual

Absorb the Bup, not the Naloxone
If used IV then immediate Withdrawal from naloxone
Practitioners need special DEA # and training

Withdrawal treatment

Methadone
Buprenorphine
Clonidine ++

Intrinsic Activity: Full Agonist (Methadone), Partial

Agonist (Buprenorphine), Antagonist (Naloxone)
100
90

Full Agonist
(Methadone)

80
70
Intrinsic Activity 60

Partial Agonist
(Buprenorphine)

50
40
30
20
10

Antagonist (Naloxone)

0
-10

-9

-8

-7

Log Dose of Opioid

-6

-5

-4

Figure 3: Induction for Patient Physically Dependent

On Short-acting Opioids, Day 1
Patient dependent on short-acting opioids?
Yes
Withdrawal symptoms
present 12-24 hrs
after last use of opioids?

No

Yes

Stop;
not dependent
on short-acting
opioids

Give buprenorphine
2-4 mg, observe 2+ hrs
Withdrawal symptoms
continue or return?

No

Yes

Daily dose established.

GO TO SWITCH
DIAGRAM (Fig. 6)

No

Yes

Repeat dose up to
maximum 8 mg for first day
Withdrawal symptoms
relieved?
Yes

Withdrawal symptoms
return?

No

Manage withdrawal
symptomatically

Return next day for

continued induction.
GO TO INDUCTION DAY 2
DIAGRAM (Fig. 5)

Daily dose established.

GO TO SWITCH
DIAGRAM (Fig. 6)

Drug Interactions with Buprenorphine

Benzodiazepines and other sedating

drugs
Medications metabolized by
cytochrome P450 3A4
Opioid antagonists

Opioid agonists

Drug Alcohol Depend. 2003 Apr

1;69(3):263-72.

Related Articles, Links

Opioid detoxification with buprenorphine, clonidine, or methadone in

hospitalized heroin-dependent patients with HIV infection.
Umbricht A, Hoover DR, Tucker MJ, Leslie JM, Chaisson RE, Preston KL.
In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of
withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an
inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine
(n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported
measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically
indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following
the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain
decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short
opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medicati
taper.
There were no significant differences of pain decline and other measures of withdrawal between the three treatment
groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the
patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine,
clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Other Addiction Meds

Relapse preventionAlcohol

Naltrexoneopiate system

AcamprosateGABA system??......... just

released and being evaluated in large
current studies

NALTREXONE IN THE TREATMENT

OF ALCOHOL DEPENDENCE

Volpicelli et al., 1992

% of Abstinent Patients

ACAMPROSATE RELAPSE RATES

Addiction. 2004 Jul;99(7):811-28.

Related Articles, Links

Efficacy and safety of naltrexone and acamprosate in the treatment of

alcohol dependence: a systematic review.
Carmen B, Angeles M, Ana M, Maria AJ.

Findings Thirty-three studies met the inclusion criteria.

Acamprosate was associated with a significant improvement in abstinence rate [odds
ratio (OR): 1.88 (1.57, 2.25), P < 0.001] and days of cumulative abstinence [WMD: 26.55
(17.56, 36.54].
Short-term administration of naltrexone reduced the relapse rate significantly [OR: 0.62
(0.52, 0.75), P < 0.001], but was not associated with a significant modification in the
abstinence rate [OR: 1.26 (0.97,1.64), P = 0.08].
There were insufficient data to ascertain naltrexone's efficacy over more prolonged periods.
Acamprosate had a good safety pattern and was associated with a significant
improvement in treatment compliance [OR: 1.29 (1.13,1.47), P < 0.001]. Naltrexone's side
effects were more numerous, yet the drug was nevertheless tolerated acceptably without
being associated with a lower adherence to treatment (OR: 0.94 (0.80, 1.1), P = 0.5). However,
overall compliance was relatively low with both medications.

Medications in Patients with

Addictions.potential
problems

Can reinforce addiction denial if Alc/Drg intervention is not

integrated and supportedesp by the prescriber..

Can be expensive, cause side effects, could be used in overdose.

Encumber the pt with seeing MD, or mental health system, cost,

convenience etc.ie make sure they are really necessary.

Active participation in recovery can be both antidep and antianx

but if serious psych problems continue, or disrupt recovery, meds
should be considered

For more serious problems such as psychosis and mania,

immediate use of medications is indicated

Sleep in recovering
Alc/Addicts

Abnormal for weeks/months in most

Is this normal toxicity and to be
tolerated
Poor sleep associated with relapse,
anx, dep, PTSD, and PROTRACTED
WITHDRAWAL

Medications for sleep in

recovering addicts/alcoholics

Treat the comorbid disorder causing the sleep

problem.ie dep/anx etc, with an antidepressant

And/or protracted withdrawal..with anticonvulsants

( for one to several months)

Prazosin for PTSD nightmares

Anti histamines, trazedone, remeron as non-specific aids

If using BZPs, oxazepam and librium

Anticonvulsants

Role in alc withdrawal acute and/or protracted

Role in bipolar, esp rapid cycle

Role in early antipsychotic augmentation

Great for ongoing sleep problems... Is this protracted

withdrawal?

Is there a role in craving/relapse prevention?

Is there a role for PRN use in agitated Dual pts, such as 500 mg
valproate, 600 mg gabapentin etc??

Anticonvulsants in alcohol
withdrawal

Good evidence for carbamazepine, valproate and

growing for gabapentin and topiramate

May even be superior in terms of safety, ability

for take home doses and in some studies, even
anxiety/agitation

Have been shown effective in high dose BZP

dependence

Stay Cool and

Keep Calm