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
3
HL
LL
Low
High
Systems Problems







Different
Different
Different
Different
Different
Different
Different
Laws…commitment/confid.
funding..audits etc
personnel
training
certification
sites
Norms
The Four Quadrant Framework for
Co-Occurring Disorders
A four-quadrant
conceptual framework
to guide systems
integration and resource
allocation in treating
individuals with cooccurring disorders
(NASMHPD,NASADAD,
1998; NY State; Ries,
1993; SAMHSA Report
to Congress, 2002)
High
severity
Less severe
mental disorder/
more severe
substance
abuse disorder
Less severe
mental disorder/
less severe
substance
abuse disorder
Low
severity
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 ER’s, 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)
60.0%
ODDS: 2.00
50.0%
ODDS: 1.23
ODDS: 1.18
Mild
(n=1022)
Moderate
(n=2391)
40.0%
30.0%
20.0%
10.0%
0.0%
ODDS adjusted
for age & gender
None
(n=4853)
Severe
(n=3930)
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 disorder
12.35 (3.01)
Any drug use disorder
33.05 (4.23)
*Data in parentheses are the percentages of respondents with the substance use disorders who
Grant B, JAMA 2004
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 disorder
22.07 (5.18)
Any alcohol use disorder
55.16 (6.29)
*Data in parentheses are the percentages of respondents with the substance use disorders who sought
Grant B, JAMA 2004
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
Headache
Dizziness
Fatigue
Quality of Life in Panic Disorder
Panic Disorder (N = 254)
35
Major Depression (N = 738)
Neither PDN or MD (N = 17,113)
30
28
27
25
20
%
16
15
14
12
12
11
10
5
2
2
0
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
40
Prevalence of Trauma
Male
Female
30
%
20
10
0
Witness
%
1
2
Accident Threat w/
Weapon
70
60
50
40
30
20
10
0
Physical Molestation Combat
Attack
Rape
2
Probability of PTSD
Witness
Accident
Threat w/
Weapon
Physical Molestation
Attack
Combat
Rape
Impaired Quality of Life with PTSD
100
PTSD
MDD
OCD
US Population
75
SF-36
50
Score
25
0
Vitality
SF-36 = 36 item short form health survey
Lower score = more impairment
Malik M et al. J Trauma Stress. 1999;12:387-393.
Social Function
Common Somatic 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):1887-96.
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):11721.
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 aren’t 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 think…viz
Schuckit 80% -> 20%
 This is poorly studied…maybe better with 12 step
 Sub Induced criteria are wrong
Addictions outcomes
 Meds take focus off sobriety
 Meds reinforce sobriety
 Just don’t work for this
Alcohol Clin Exp Res. 2001 Feb;25(2):210-20.
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 Inventory…easy, broad symptom mix
Others……………………………see new Co-occurring TIP in 12-04
“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 doesn’t 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 MHC’s:






MD visit q 3 months
CM visit q 2 wks…focus on ADL’s
Maybe dual dx group 1-2 hrs/wk
Limited expectations of recovery
Pschotherapy time ~ 0-2 hrs week
In the most Addictions IOP’s





MD visit 1/ 3 months, often 1’ care
CM 1:1 q 2 wks….focus on Sub use, U tox’s
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 Public’s
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 Governor’s Office of Crime Control and Prevention.
CESAR FAX may be copied without permission. Please cite CESAR as the source.
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: counselor’s role

Ask the pt about :

Compliance…


Effectiveness…




“sometimes people forget their medications…how 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 supported…esp 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 antianx…but if these problems
continue, or disrupt recovery, meds should be
considered
Antipsychotics
Alcohol Clin Exp Res. 2004 May;28(5):73645.
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
P < 0.05

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
67%
% Noncompliant

80
60
47%
40
34%
20
0
No Past
Past
Current
History History
User
Hunt GE et al. Schizophrenia Res. 2002;54:253-264.
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.
RISPERDAL® CONSTA™
Injection Kit Components
Needle Pro
SmartSite
Access
Device
®
Aqueous
Diluent
Risperidone
Microspheres
Assembled
RISPERDAL® CONSTA™
PRC approved with
changes: 11/10/03
(RISPERDAL CONSTA
Promotional slide kit)
®
Device
Safety Needle
Risperidone +
9-hydroxyrisperidone (ng/mL)
Blood Levels Over Time After
Single Dose*
PRC approved with
changes: 11/10/03
(RISPERDAL CONSTA
Promotional slide kit)
0
1
2
Antipsychotic
Supplementation
3
4
5
6
Time (wk)
*25-mg dose, N = 14.
Data on file, Janssen Pharmaceutica Products, L.P.
7
8
9
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):197-201.
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
Withdrawal symptoms
return?
No
Yes
Repeat dose up to
maximum 8 mg for first day
Withdrawal symptoms
relieved?
Yes
Daily dose established.
GO TO SWITCH
DIAGRAM (Fig. 6)
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 prevention…Alcohol


Naltrexone…opiate system
Acamprosate…GABA system??......... just
released and being evaluated in large current
studies
NALTREXONE IN THE TREATMENT OF
ALCOHOL DEPENDENCE
Cumulative Proportion with No Relapse
Cumulative Relapse Rate
1.2
1
0.8
0.6
0.4
Naltrexone HCL (N=35)
Placebo (N=35)
0.2
0
0
1
2
3
4
5
6
7
8
9
10
11
12
No. of Weeks Receiving Medication
Volpicelli et al., 1992
ACAMPROSATE RELAPSE RATES
Treatment Period
100
Follow-up Period
90
% of Abstinent Patients
80
Acamprosate
70
Placebo
60
50
40
30
20
10
0
0
24
48
Weeks
72
96
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 supported…esp 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 BZP’s, 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