Co-occurring Addiction and Co-occurring Addiction and Less SevereLess Severe

Mental Disorders Mental Disorders

Richard Ries MDRichard Ries MDrries@u.washington.edu

Harborview Medical CenterHarborview Medical CenterUniversity of WashingtonUniversity of Washington

Seattle, WaSeattle, Wa

DUAL DIAGNOSIS IS:DUAL DIAGNOSIS IS:

TWO DIAGNOSES/ DISORDERSTWO DIAGNOSES/ DISORDERS

TWO SYSTEMSTWO SYSTEMS

DOUBLE TROUBLEDOUBLE TROUBLE

IN THE EYE OF THE BEHOLDERIN THE EYE OF THE BEHOLDER

Examples of Dual Disorders:Examples of Dual Disorders:

MENTAL DISORDERSMENTAL DISORDERS SchizophreniaSchizophrenia Bi-polarBi-polar SchizoaffectiveSchizoaffective Major DepressionMajor Depression Borderline Borderline

PersonalityPersonality Post Traumatic Post Traumatic

StressStress Social PhobiaSocial Phobia othersothers

ADDICTION ADDICTION DISORDERSDISORDERS Alcohol Alcohol

Abuse/Depen.Abuse/Depen. Cocaine/ AmphetCocaine/ Amphet OpiatesOpiates MarijuanaMarijuana Polysubstance Polysubstance

combinationscombinations Prescription drugsPrescription drugs

Dual Disorders for Dual Disorders for Everyone?Everyone?

If applied to all cases, Term has no meaningIf applied to all cases, Term has no meaning (eg Spider phobia and (eg Spider phobia and ““Running AddictionRunning Addiction””))

Both Mental and Addiction Disorders need to be Both Mental and Addiction Disorders need to be over thresholdover threshold

Personality Disorders, other than Borderline not Personality Disorders, other than Borderline not usually countedusually counted

Substance Induced Disorders cause diagnostic Substance Induced Disorders cause diagnostic confusionconfusion

CHARACTERISTICS OF THE DUAL DIAGNOSIS CHARACTERISTICS OF THE DUAL DIAGNOSIS CLIENT IN KING COUNTY… CLIENT IN KING COUNTY… Ries Ries ‘‘8989

Severity of Chemical Dependency

High

Severity of Psychiatric Low Condition

Low

High

1

2

4 3

LH HH

LL HL

Systems ProblemsSystems Problems

Different Laws…commitment/confid.Different Laws…commitment/confid. Different funding..audits etcDifferent funding..audits etc Different personnelDifferent personnel Different trainingDifferent training Different certificationDifferent certification Different sitesDifferent sites Different NormsDifferent Norms

The Four Quadrant Framework for The Four Quadrant Framework for Co-Occurring DisordersCo-Occurring Disorders

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

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

Less severemental disorder/

less severe substance

abuse disorder

More severemental disorder/

less severe substance

abuse disorder

More severemental disorder/

more severe substance

abuse disorder

Less severemental disorder/

more severe substance

abuse disorder

High severity

High severity

Lowseverity

DOUBLE TROUBLEDOUBLE TROUBLE

Hall ’77 Poor out-pt attendance, discontinue Rx Alterman ’85 More mood changes, intensive staffing Solomon ’86 More noncompliance, arrests Safer ’87 Over twice hosp. rate and criminal behav Drake ’89 More hostility, noncompliance Barbee ’89 More psych symptoms Lyons ’89 More noncompliance, ER, jail, rehosp. Chen ’92 Worse treatment course

But what about But what about NONNON- severely - severely mentally ill co-occurring pts?mentally ill co-occurring pts?

Like in Addiction Treatment settingsLike in Addiction Treatment settings

Like in Criminal Justice settingsLike in Criminal Justice settings

Like in Primary Care SettingsLike in Primary Care Settings

Like in ERLike in ER’’s, especially with suicidal ptss, especially with suicidal pts

The new TIP will bring more focus on these The new TIP will bring more focus on these populationspopulations

Likelihood of a Suicide AttemptLikelihood of a Suicide Attempt

Risk FactorRisk Factor

Cocaine useCocaine use Major DepressionMajor Depression Alcohol useAlcohol use Separation or DivorceSeparation or Divorce

NIMH/NIDANIMH/NIDA

Increased Odds Of Increased Odds Of Attempting Attempting SuicideSuicide

62 times more likely62 times more likely

41 times more likely41 times more likely

8 times more likely8 times more likely

11 times more likely11 times more likely

ECA EVALUATIONECA EVALUATION

Double TroubleDouble Trouble::RELATIONSHIP OF ALCOHOL & DRUG PROBLEMSRELATIONSHIP OF ALCOHOL & DRUG PROBLEMS

TO SEVERE SUICIDALITY (n=12,196)TO SEVERE SUICIDALITY (n=12,196)

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

None (n=4853)

Mild (n=1022)

Moderate(n=2391)

Severe(n=3930)

ODDS: 1.23 ODDS: 1.18

ODDS: 2.00

ALCOHOL OR DRUG PROBLEMS

Perc

en

t W

ith

Severe

Su

icid

e R

ati

ng

Walds = 235.41 p < .001 Ries & Russo unpub , 2003

ODDS adjusted for age & gender

Drug Induced PsychopathologyDrug Induced Psychopathology

Drug StatesDrug States WithdrawalWithdrawal

AcuteAcute ProtractedProtracted

IntoxicationIntoxication Chronic UseChronic Use

Symptom Symptom GroupsGroups

DepressionDepression AnxietyAnxiety PsychosisPsychosis ManiaMania

Rounsaville Rounsaville ‘‘9090

Twelve-Month Prevalence of DSM-IV Independent Mood and Twelve-Month Prevalence of DSM-IV Independent Mood and Anxiety Disorders Among Respondents with DSM-IV Anxiety Disorders Among Respondents with DSM-IV

Substance Use Disorders Who Sought Treatment in the Past Substance Use Disorders Who Sought Treatment in the Past 12 Months12 Months

DisorderDisorder Respondents, % (SE)Respondents, % (SE)

Those With Any Alcohol Use Disorder (5.81%)*Those With Any Alcohol Use Disorder (5.81%)*Any mood disorderAny mood disorder 40.6940.69 (4.11)(4.11)

Major DepressionMajor Depression 32.7532.75 (4.01)(4.01)DysthymiaDysthymia 11.0111.01 (2.74)(2.74)ManiaMania 12.5612.56 (2.81)(2.81)HypomaniaHypomania 3.073.07 (1.37)(1.37)

Any anxiety disorderAny anxiety disorder 33.3833.38 (4.17)(4.17)Panic disorderPanic disorder With agoraphobiaWith agoraphobia 4.104.10 (1.54)(1.54) Without agoraphobiaWithout agoraphobia 9.109.10 (2.48)(2.48)Social phobiaSocial phobia 8.498.49 (3.48)(3.48)Specific phobiaSpecific phobia 17.2417.24 (3.10)(3.10)Generalized anxiety Generalized anxiety

disorderdisorder 12.3512.35 (3.01)(3.01)

Any drug use disorderAny drug use disorder 33.0533.05 (4.23)(4.23)*Data in parentheses are the percentages of respondents with the substance use *Data in parentheses are the percentages of respondents with the substance use disorders who sought treatment in the past 12 months.disorders who sought treatment in the past 12 months.

Grant B, JAMA 2004

Twelve-Month Prevalence of DSM-IV Independent Mood and Twelve-Month Prevalence of DSM-IV Independent Mood and Anxiety Disorders Among Respondents with DSM-IV Anxiety Disorders Among Respondents with DSM-IV

Substance Use Disorders Who Sought Treatment in the Past Substance Use Disorders Who Sought Treatment in the Past 12 Months12 Months

DisorderDisorder Respondents, % (SE)Respondents, % (SE)

Those With Any Drug Use Disorder (13.10%)*Those With Any Drug Use Disorder (13.10%)*Any mood disorderAny mood disorder 60.3160.31 (5.86)(5.86)

Major DepressionMajor Depression 44.2644.26 (6.28)(6.28)DysthymiaDysthymia 25.9125.91 (5.19)(5.19)ManiaMania 20.3920.39 (5.17)(5.17)HypomaniaHypomania 2.482.48 (1.67)(1.67)

Any anxiety disorderAny anxiety disorder 42.6342.63 (5.97)(5.97)Panic disorderPanic disorder With agoraphobiaWith agoraphobia 5.925.92 (2.19)(2.19) Without agoraphobiaWithout agoraphobia 8.648.64 (3.05)(3.05)Social phobiaSocial phobia 12.0912.09 (3.48)(3.48)Specific phobiaSpecific phobia 22.5222.52 (4.99)(4.99)Generalized anxiety Generalized anxiety

disorderdisorder 22.0722.07 (5.18)(5.18)

Any alcohol use disorderAny alcohol use disorder 55.1655.16 (6.29)(6.29)*Data in parentheses are the percentages of respondents with the substance use *Data in parentheses are the percentages of respondents with the substance use disorders who sought treatment in the past 12 months.disorders who sought treatment in the past 12 months.

Grant B, JAMA 2004

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

50% to 65% of panic disorder patients have depression†

11% of social anxiety disorder patients have OCD**

67% of OCD patients have depression*

70% of social anxiety disorder patients have depression

Comorbidity of Comorbidity of Depression and Anxiety Depression and Anxiety

DisordersDisorders

Depression

OCD

Social Anxiety Disorder

Panic Disorder

HIGHLY COMMON…

HIGHLY COMORBID

Diagnostic Criteria for Diagnostic Criteria for Panic AttackPanic Attack

• Palpitations, pounding heart

• Sweating

• Trembling or shaking

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

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:

Diagnostic Criteria for Diagnostic Criteria for Panic Attack ContinuedPanic 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

Fatigue

Gastro-intestinal

Symptoms

SOMATIC SYMPTOMS

Headache

Chest Pain

Dizziness

Somatic Symptoms In Somatic Symptoms In Panic Disorder Panic Disorder

12

28 27

14

11

16

2 2

12

0

5

10

15

20

25

30

35

Panic Disorder (N = 254)

Major Depression (N = 738)

Neither PDN or MD (N = 17,113)

Quality of Life in Panic DisorderQuality of Life in Panic Disorder

%

Markowitz et al. Arch Gen Psychiatry. 1989;46:984.

Marital Discord(past 2 weeks)

Use Of ER(past year)

Financial Dependence(welfare or disability)

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

DSM-IV Diagnostic DSM-IV Diagnostic Criteria for PTSDCriteria for PTSD

Exposure to a traumatic event in which Exposure to a traumatic event in which the person:the person: experienced, witnessed, or was experienced, witnessed, or was

confronted by death or serious injury to confronted by death or serious injury to self or others self or others AND AND

responded with intense fear, responded with intense fear, helplessness, helplessness, or horroror horror

DSM-IV Diagnostic DSM-IV Diagnostic Criteria for PTSD Criteria for PTSD

ContinuedContinued Symptoms Symptoms

appear in 3 symptom clusters: re-appear in 3 symptom clusters: re-experiencing, avoidance/numbing, experiencing, avoidance/numbing, hyperarousalhyperarousal

last for > 1 monthlast for > 1 month cause clinically significant distress or cause clinically significant distress or

impairment in functioningimpairment in functioning

DSM-IV Diagnostic Criteria DSM-IV Diagnostic Criteria for PTSD Re-experiencingfor PTSD Re-experiencing

Persistent re-experiencing of Persistent re-experiencing of 1 of the following: 1 of the following: recurrent distressing recollections of eventrecurrent distressing recollections of event recurrent distressing dreams of eventrecurrent distressing dreams of event acting or feeling event was recurringacting or feeling event was recurring psychological distress at cues resembling eventpsychological distress at cues resembling event physiological reactivity to cues resembling physiological reactivity to cues resembling

eventevent

DSM-IV Diagnostic Criteria for DSM-IV Diagnostic Criteria for PTSD Avoidance/NumbingPTSD Avoidance/Numbing

Avoidance of stimuli and numbing of general Avoidance of stimuli and numbing of general responsiveness indicated by responsiveness indicated by 3 of the following: 3 of the following: avoid thoughts, feelings, or conversations*avoid thoughts, feelings, or conversations* avoid activities, places, or people*avoid activities, places, or people* inability to recall part of traumainability to recall part of trauma interest in activitiesinterest in activities estrangement from othersestrangement from others restricted range of affectrestricted range of affect sense of foreshortened futuresense of foreshortened future

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

DSM-IV Diagnostic DSM-IV Diagnostic Criteria for PTSD Criteria for PTSD

HyperarousalHyperarousal Persistent symptoms of increased arousal Persistent symptoms of increased arousal 2: 2:

difficulty sleepingdifficulty sleeping irritability or outbursts of angerirritability or outbursts of anger difficulty concentratingdifficulty concentrating hypervigilancehypervigilance exaggerated startle responseexaggerated startle response

Prevalence of Trauma and Prevalence of Trauma and Probability of PTSDProbability of PTSD

Probability of PTSD

010203040506070

Witness Accident Threat w/Weapon

PhysicalAttack

Molestation Combat Rape

%

Prevalence of Trauma

0

10

20

30

40

%

Male

Female

Witness Accident Threat w/Weapon

PhysicalAttack

Molestation Combat Rape

1

2

1

2

0

25

50

75

100

Vitality Social Function

PTSD

MDD

OCD

US Population

Impaired Quality of Life with Impaired Quality of Life with PTSDPTSD

SF-36 = 36 item short form health surveyLower score = more impairmentMalik M et al. J Trauma Stress. 1999;12:387-393.

SF-36 Score

Common Somatic Common Somatic Complaints Of Social Complaints Of Social

Anxiety DisorderAnxiety Disorder

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

Blushing

Sweating

Trembling And Shaking

“Butterflies”

PalpitationsPalpitations

StutteringStuttering

Social Anxiety DisorderSocial Anxiety DisorderSPIN ScreenerSPIN Screener

Is being embarrassed or looking stupid Is being embarrassed or looking stupid among your worst fears?among your worst fears?

Does fear of embarrassment cause you to Does fear of embarrassment cause you to avoid doing things or speaking to others?avoid doing things or speaking to others?

Do you avoid activities in which you are the Do you avoid activities in which you are the center of attention?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.

-20.0

-15.0

-10.0

-5.0

0.0

Impairment**(%)

* 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.

Wages CollegeGraduation

ProfessionalOr

Management Positions

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

Therapy PlanTherapy Plan

PsychPsychBioBio LabsLabs

Meds (anti-Meds (anti-depressants, depressants, etc.)etc.)

Psych Psych psychotherapy psychotherapy education groupseducation groupsprocess groupsprocess groups

SocialSocial Couples conf.Couples conf.D/C planningD/C planninghousing, etc.housing, etc.

CDCDLabsLabsMeds (withdrawal, craving, Meds (withdrawal, craving,

etc.)etc.)

Step workStep workGroupsGroups

AA MeetingsAA MeetingsInterventionInterventionSober housingSober housing

1: 1: JAMA. 2004 Apr 21;291(15):1887-JAMA. 2004 Apr 21;291(15):1887-96. 96.

Related Articles, LinksLinks               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. Psychopharmacol Bull. 1998;34(1):117-21. 1998;34(1):117-21.

Related Articles, LinksLinks

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

Related Articles, LinksLinks

                      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 arenWhy aren’’t Antidepressants more t Antidepressants more effective in addictions patients?effective in addictions patients?

Psychiatric outcomes:Psychiatric outcomes: Antidepressants only beat placebo by 20% anyway in Antidepressants only beat placebo by 20% anyway in

NON addictsNON addicts Study patients also get Study patients also get ““addiction rxaddiction rx”” Maybe addiction rx is more anti-dep, anti anx than we Maybe addiction rx is more anti-dep, anti anx than we

think…viz Schuckit 80% -> 20%think…viz Schuckit 80% -> 20% This is poorly studied…maybe better with 12 stepThis is poorly studied…maybe better with 12 step Sub Induced criteria are wrongSub Induced criteria are wrong

Addictions outcomesAddictions outcomes Meds take focus off sobrietyMeds take focus off sobriety Meds reinforce sobrietyMeds reinforce sobriety Just donJust don’’t work for thist work for this

Alcohol Clin Exp Res. 2001 Alcohol Clin Exp Res. 2001 Feb;25(2):210-20. 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 Can encouraging substance abuse patients to participate in self-help groups reduce demand for participate in self-help groups reduce demand for

health care? health care? A quasi-experimental studyA quasi-experimental study

n=1774, 1 year follow-upn=1774, 1 year follow-up Humphreys et al ..2001Humphreys et al ..2001

Outpt Inpt days AbstinenceOutpt Inpt days Abstinence

VisitsVisits Rates Rates

12 Step 13.1 10.5 45.712 Step 13.1 10.5 45.7

Cog Beh 17 17 36.2Cog Beh 17 17 36.2

* all p< .001 ** 64% higher cost for CBT* all p< .001 ** 64% higher cost for CBT

Dual Screening:Dual Screening:

the the ““Dual CageDual Cage””…………….easy, but no data…………….easy, but no data ASAM pt placement………..needs experience, little or no ASAM pt placement………..needs experience, little or no

datadata ASI psych…………………….short, available, good screening, ASI psych…………………….short, available, good screening,

good datagood data Beck, Zung, Ham D etc…..easy, good data, may be limitedBeck, Zung, Ham D etc…..easy, good data, may be limited Brief Symptom Inventory…easy, broad symptom mixBrief Symptom Inventory…easy, broad symptom mix Others……………………………see new Co-occurring TIP in 12-Others……………………………see new Co-occurring TIP in 12-

0404

““Dual CAGEDual CAGE”” QUESTIONS QUESTIONS

Cut Down (or stopped)Cut Down (or stopped) Because mental symptoms worsenedBecause mental symptoms worsened Because MH doctor or therapist suggestedBecause MH doctor or therapist suggested

Annoyed when drug/alc. use discussedAnnoyed when drug/alc. use discussed Annoyed, anxious or angry,… fights when usingAnnoyed, anxious or angry,… fights when using Admitted to ER or hospital for psych when using or Admitted to ER or hospital for psych when using or

notnot ADHD when childADHD when child

Guilty about useGuilty about use Guilty, depressed, suicidal when using or notGuilty, depressed, suicidal when using or not Ever made a suicide attempt when using or notEver made a suicide attempt when using or not

CAGE QuestionsCAGE Questions

Eye opener: taken drink or drug in AM to Eye opener: taken drink or drug in AM to feel betterfeel better Taken a drink or drug to blot out Taken a drink or drug to blot out

symptomssymptoms Taken drink or drug with psych medTaken drink or drug with psych med Not taken meds because of using Not taken meds because of using

drug/alc (forgot, avoid mixing, etc.)drug/alc (forgot, avoid mixing, etc.)

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

stop or cut down?stop or cut down?

MedicationsMedications

Essential to Treatment of Severely Essential to Treatment of Severely Mentally IllMentally Ill Substance Use and Not-Taking Meds are the 2 Substance Use and Not-Taking Meds are the 2

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

For Dep/Anx, less clearFor Dep/Anx, less clear Personal experience shows maximizing 12 step Personal experience shows maximizing 12 step

AND use of meds is best rxAND use of meds is best rx

It may It may notnot be that the med(s) be that the med(s) stopped working, but……stopped working, but……

The patient stopped the medThe patient stopped the med The patient stopped the med AND used The patient stopped the med AND used

drugs and/or alcohol…...drugs and/or alcohol…... OR lowered the med and used…OR lowered the med and used… OR used on top of the med….OR used on top of the med…. OR used twice the dose on one day and OR used twice the dose on one day and

nothing the next….nothing the next…. Stimulants ( cocaine/amphets) are most Stimulants ( cocaine/amphets) are most

MSE destructive.MSE destructive.

How to use AA as a treatment How to use AA as a treatment partnerpartner

1. Know something about AA, its history, 1. Know something about AA, its history, presence in your community, structure presence in your community, structure and contentand content

2. Helpful Readings:2. Helpful Readings: Brown: A psychological view of the 12 stepsBrown: A psychological view of the 12 steps AA: AA: AA for the medical practitionerAA for the medical practitioner; and ; and The AA member and medicationsThe AA member and medications Twelve Step Facilitation Therapy Manual-Twelve Step Facilitation Therapy Manual-

Project Match, NIAAA web siteProject Match, NIAAA web site Forman: Forman: ““One AA Meting doesnOne AA Meting doesn’’t fit allt 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) Double Trouble Recovery (DTR) OutcomesOutcomes

Members of 24 DTR groups (n=240) New York Members of 24 DTR groups (n=240) New York City, 1 year outcomesCity, 1 year outcomes

Drug/alcohol abstinence = 54% at baseline, Drug/alcohol abstinence = 54% at baseline, increased to 72% at follow-up. increased to 72% at follow-up.

More attendance = better Medication adherence,More attendance = better Medication adherence,

Better Medication adherence = less hospitalizationBetter Medication adherence = less hospitalization

Magura Add Beh 2003, Psych Serv 2002Magura Add Beh 2003, Psych Serv 2002

Dual Dep/Anx RX planDual Dep/Anx RX plan

Differential DxDifferential Dx 12 step facilitation12 step facilitation Meds if indicated ( and I often use Meds if indicated ( and I often use

them)them) Visits:Visits:

Ries 1/week ( 12 step facil and meds)Ries 1/week ( 12 step facil and meds) AA 3x week or 90 in 90AA 3x week or 90 in 90 Meet with sponsorMeet with sponsor Meet with familyMeet with family

Low mental illness/High addictions outpt Low mental illness/High addictions outpt getsgets

In most MHCIn most MHC’’s:s: MD visit q 3 monthsMD visit q 3 months CM visit q 2 wks…focus on ADLCM visit q 2 wks…focus on ADL’’ss Maybe dual dx group 1-2 hrs/wkMaybe dual dx group 1-2 hrs/wk Limited expectations of recoveryLimited expectations of recovery Pschotherapy time ~ 0-2 hrs weekPschotherapy time ~ 0-2 hrs week

In the most Addictions IOPIn the most Addictions IOP’’ss MD visit 1/ 3 months, often 1MD visit 1/ 3 months, often 1’’ care care CM 1:1 q 2 wks….focus on Sub use, U toxCM 1:1 q 2 wks….focus on Sub use, U tox’’ss IOP group 3 hrs-3x weekIOP group 3 hrs-3x week Expectations of Sobriety/progressExpectations of Sobriety/progress Psychotherapy time 3-10 hrs week ( plus more AA)Psychotherapy time 3-10 hrs week ( plus more AA)

Report Questions Ability of National Treatment Infrastructure to Deliver Quality Care

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.

Percentage of Programs

Closed or Stopped Services

Reorganized Director in Position Less Than

One Year

No Information Services, E-mail,

or Voicemail

0%

20%

40%

60%

80%

100%

15%25%

54%

20%

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.

New Issues in Medications for New Issues in Medications for

Co-occurring Addiction and Co-occurring Addiction and Mental DisordersMental Disorders

Richard Ries MDRichard Ries MD

Medication monitoring and Medication monitoring and motivatingmotivating

Know who is on what and what forKnow who is on what and what for

Know the prescriber if possibleKnow the prescriber if possible Sit in on med sessions onsiteSit in on med sessions onsite Talk to off-site doctor or nurse Talk to off-site doctor or nurse PRE problem!!!PRE problem!!!

Know something about meds…Know something about meds… ATTC Tech transfer centers summaryATTC Tech transfer centers summary New COD TIP ( Dec 04)New COD TIP ( Dec 04) NIMH web site, NAMI web siteNIMH web site, NAMI web site

Medications: counselorMedications: counselor ’’s s rolerole

Ask the pt about :Ask the pt about : Compliance… Compliance…

““sometimes people forget their medications…how often does sometimes people forget their medications…how often does this happen to you?this happen to you?”” …ie % not taking …ie % not taking

Effectiveness… Effectiveness… ““how well do you think the meds are working?…how well do you think the meds are working?… what do you notice…what do you notice… here is what I noticehere is what I notice

Side Effects…. Side Effects…. ““ are you having any side effects to the medication?…are you having any side effects to the medication?… what are they…what are they… have you told the prescriber?have you told the prescriber? do you need help with talking to the presciber?do you need help with talking to the presciber?

Medications….potential Medications….potential problemsproblems

Can reinforce addiction denial if recovery is Can reinforce addiction denial if recovery is not integrated and supported…esp by the not integrated and supported…esp by the prescriber..( so work with them)prescriber..( so work with them)

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

Encumber the pt with seeing MD, or mental Encumber the pt with seeing MD, or mental health system, cost, convenience etc….ie health system, cost, convenience etc….ie make sure they are really necessary.make sure they are really necessary.

Active participation in recovery can be both Active participation in recovery can be both antidep and antianx…but if these problems antidep and antianx…but if these problems continue, or disrupt recovery, meds should be continue, or disrupt recovery, meds should be considered considered

AntipsychoticsAntipsychotics

Alcohol Clin Exp Res. 2004 Alcohol Clin Exp Res. 2004 May;28(5):736-45. 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 J Clin Psychopharmacol. 2000 Feb;20(1):94-8. 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.

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.

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

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 Schizophr Res. 2003 Mar 1;60(1):81-5. 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. Eur J Pharmacol. 2003 May 2003 May 9;468(2):121-7. 9;468(2):121-7.

                 Risperidone reduces limited access alcohol drinking in alcohol-preferring 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 Comorbid Substance Abuse Associated With Noncompliance in SchizophreniaWith Noncompliance in Schizophrenia

Nearly half of all patients in Nearly half of all patients in a prospective 4-year study a prospective 4-year study (N = 99) were active (N = 99) were active substance abusers (n = substance abusers (n = 42) 42)

Patients who actively Patients who actively abused substances were abused substances were significantly more likely to significantly more likely to be noncompliantbe noncompliant

67%

47%

34%

0

20

40

60

80

No PastHistory

PastHistory

CurrentUser

P < 0.05P < 0.05

% N

onco

mpl

iant

% N

onco

mpl

iant

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

It may not be that the It may not be that the med(s) stopped working, med(s) stopped working,

but……but…… The patient stopped the medThe patient stopped the med The patient stopped the med AND The patient stopped the med AND

used drugs and/or alcohol…...used drugs and/or alcohol…... OR lowered the med and used…OR lowered the med and used… OR used on top of the med….OR used on top of the med…. OR used twice the dose on one day OR used twice the dose on one day

and nothing the next….and nothing the next…. Stimulants ( cocaine/amphets) are Stimulants ( cocaine/amphets) are

most MSE destructive.most MSE destructive.

RISPERDALRISPERDAL®® CONSTA CONSTA™™ Injection Kit ComponentsInjection Kit Components

Needle ProNeedle Pro®® Device DeviceSafety NeedleSafety NeedleSmartSiteSmartSite®®

Access Access DeviceDevice

Risperidone Risperidone MicrospheresMicrospheres

Aqueous Aqueous DiluentDiluent

Assembled Assembled

RISPERDALRISPERDAL®® CONSTA CONSTA™™

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

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

*25-mg dose, N = 14.Data on file, Janssen Pharmaceutica Products, L.P.

Ris

per

ido

ne

+9-

hyd

roxy

risp

erid

on

e (n

g/m

L)

Time (wk)

0 1 2 3 4 5 6 7 8 9 10 11 12

Blood Levels Over Time Blood Levels Over Time After Single Dose*After Single Dose*

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

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

Antipsychotic Supplementation

Substance Induced PsychosesSubstance Induced Psychoses

Amphet/MethamphetaminesAmphet/Methamphetamines CocaineCocaine EcstacyEcstacy

Hallucinogens ( strong THC too)Hallucinogens ( strong THC too) Other Rave DrugsOther Rave Drugs Alcohol WD and HallucinosisAlcohol WD and Hallucinosis

AnticonvulsantsAnticonvulsants

COMPARING THE KNOWN EFFICACY OF COMPARING THE KNOWN EFFICACY OF ANTIEPILEPTIC AGENTS IN BIPOLAR DISORDERANTIEPILEPTIC AGENTS IN BIPOLAR DISORDER

Drug Mania Depression Maintenance Comments

Valproate New Depakote ERFormulation

Carbamzepine 2 new maintenance studiesv. lithium

Gabapentin — 2 negative placebo-controlled studies in mania

Lamotrigine Antidepressant activity inseveral controlled trials

Topiramate Dose-related weight loss

Key: Efficacy demonstrated in > 2 placebo-controlled trials

Efficacy demonstrated in one placebo-controlled or two large, activecomparator 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 availableKeck & McElroy, 2002

COMPARING THE KNOWN EFFICACY OF COMPARING THE KNOWN EFFICACY OF ANTIEPILEPTIC AGENTS IN BIPOLAR DISORDERANTIEPILEPTIC AGENTS IN BIPOLAR DISORDER

Drug Mania Depression Maintenance Comments

Oxcarbazepine Improved tolerability &pharmacokinetics

Zonisamide ND ND May produce weight lossin some patients

Tiagabine ND ND More data neededregarding tolerability and

efficacy

Levetiracetam ND ND ND Data needed regardingefficacy and tolerability

Key: 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

ND No data presently available

Keck & McElroy, 2002

Eur Neuropsychopharmacol. 2004 Eur Neuropsychopharmacol. 2004 Aug;14(4):319-23. Aug;14(4):319-23.

Related Articles, LinksLinks

                 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 Am J Addict 2002 Spring;11(2):141-50Spring;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 Alcohol Clin Exp Res 2001 Sep;25(9):1324-9Sep;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-Psychiatr Serv. 2000 May;51(5):634-8. 8.

Related Articles, LinksLinks

                     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. Psychiatr Serv. 2004 Mar;55(3):290-4. Related Articles, LinksLinks

                        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 J Clin Psychopharmacol. 2001 Feb;21(1):21-6. Feb;21(1):21-6.

Related Articles, LinksLinks

                        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 early-augmentation 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 olanzapine-topiramate 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. 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. 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-J Clin Psychiatry. 2003 Feb;64(2):197-201. 201.

Related Articles,Related Articles, LinksLinks

                    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 MedsAnti-opiate Addiction Meds Harm reduction:..opiatesHarm reduction:..opiates

MethadoneMethadone Only through Methadone agencies for AddictionOnly through Methadone agencies for Addiction Confusion when injury/pain/addiction co-occurrConfusion when injury/pain/addiction co-occurr

LAAM.LAAM. Due to liver prolems ( minor) is being phased outDue to liver prolems ( minor) is being phased out

BuprenorphineBuprenorphine Not given orallyNot given orally

SuboxoneSuboxone Combination of Bup plus Naloxone subligualCombination of Bup plus Naloxone subligual Absorb the Bup, not the NaloxoneAbsorb the Bup, not the Naloxone If used IV then immediate Withdrawal from naloxoneIf used IV then immediate Withdrawal from naloxone Practitioners need special DEA # and trainingPractitioners need special DEA # and training

Withdrawal treatmentWithdrawal treatment MethadoneMethadone BuprenorphineBuprenorphine Clonidine ++Clonidine ++

-10 -9 -8 -7 -6 -5 -40

10

20

30

40

50

60

70

80

90

100

Intrinsic Activity

Log Dose of Opioid

Full Agonist(Methadone)

Partial Agonist(Buprenorphine)

Antagonist (Naloxone)

Intrinsic Activity: Full Agonist (Methadone), Partial Agonist (Buprenorphine), Antagonist (Naloxone)

Patient dependent on short-acting opioids?

Withdrawal symptomspresent 12-24 hrs

after last use of opioids?

Give buprenorphine2-4 mg, observe 2+ hrs

Withdrawal symptomscontinue or return?

Repeat dose up tomaximum 8 mg for first day

Withdrawal symptomsrelieved?

Manage withdrawalsymptomatically

Yes

Yes

No

Stop;not dependenton short-acting

opioids

No

Yes

Yes

Figure 3: Induction for Patient Physically DependentOn Short-acting Opioids, Day 1

Withdrawal symptomsreturn?

Daily dose established.GO TO SWITCH

DIAGRAM (Fig. 6)

No Daily dose established.GO TO SWITCH

DIAGRAM (Fig. 6)

No

Return next day forcontinued induction.

GO TO INDUCTION DAY 2DIAGRAM (Fig. 5)

Yes

Benzodiazepines and other sedating Benzodiazepines and other sedating drugsdrugs

Medications metabolized by Medications metabolized by cytochrome P450 3A4cytochrome P450 3A4

Opioid antagonistsOpioid antagonists

Opioid agonistsOpioid agonists

Drug Interactions with Buprenorphine

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 medicatitaper.

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 MedsOther Addiction Meds

Relapse prevention…AlcoholRelapse prevention…Alcohol Naltrexone…opiate systemNaltrexone…opiate system

Acamprosate…GABA system??......... just Acamprosate…GABA system??......... just released and being evaluated in large released and being evaluated in large current studiescurrent studies

NALTREXONE IN THE TREATMENT NALTREXONE IN THE TREATMENT OF ALCOHOL DEPENDENCEOF ALCOHOL DEPENDENCE

Cumulative Relapse Rate

0

0.2

0.4

0.6

0.8

1

1.2

0 1 2 3 4 5 6 7 8 9 10 11 12No. of Weeks Receiving Medication

Cu

mu

lati

ve P

rop

ort

ion

wit

h N

o R

elap

se

Naltrexone HCL (N=35)Placebo (N=35)

Volpicelli et al., 1992

ACAMPROSATE RELAPSE RATESACAMPROSATE RELAPSE RATES

0

10

20

30

40

50

60

70

80

90

100

Acamprosate Placebo

24 480 72 96

Treatment Period Follow-up Period

Weeks

% o

f A

bst

inen

t P

atie

nts

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 Medications in Patients with Addictions….potential Addictions….potential

problemsproblems Can reinforce addiction denial if Alc/Drg intervention is not Can reinforce addiction denial if Alc/Drg intervention is not

integrated and supported…esp by the prescriber..integrated and supported…esp by the prescriber..

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

Encumber the pt with seeing MD, or mental health system, cost, Encumber the pt with seeing MD, or mental health system, cost, convenience etc….ie make sure they are really necessary.convenience etc….ie make sure they are really necessary.

Active participation in recovery can be both antidep and antianx…Active participation in recovery can be both antidep and antianx…but if serious psych problems continue, or disrupt recovery, meds but if serious psych problems continue, or disrupt recovery, meds should be considered should be considered

For more serious problems such as psychosis and mania, For more serious problems such as psychosis and mania, immediate use of medications is indicatedimmediate use of medications is indicated

Sleep in recovering Sleep in recovering Alc/AddictsAlc/Addicts

Abnormal for weeks/months in mostAbnormal for weeks/months in most Is this Is this ““normal toxicitynormal toxicity”” and to be and to be

toleratedtolerated Poor sleep associated with relapse, Poor sleep associated with relapse,

anx, dep, PTSD, and PROTRACTED anx, dep, PTSD, and PROTRACTED WITHDRAWAL WITHDRAWAL

Medications for sleep in Medications for sleep in recovering addicts/alcoholicsrecovering addicts/alcoholics

Treat the comorbid disorder causing the sleep Treat the comorbid disorder causing the sleep problem….ie dep/anx etc, with an antidepressantproblem….ie dep/anx etc, with an antidepressant

And/or protracted withdrawal…..with anticonvulsants ( And/or protracted withdrawal…..with anticonvulsants ( for one to several months)for one to several months)

Prazosin for PTSD nightmaresPrazosin for PTSD nightmares

Anti histamines, trazedone, remeron as non-specific Anti histamines, trazedone, remeron as non-specific aidsaids

If using BZPIf using BZP’’s, oxazepam and libriums, oxazepam and librium

AnticonvulsantsAnticonvulsants Role in alc withdrawal acute and/or protractedRole in alc withdrawal acute and/or protracted

Role in bipolar, esp rapid cycleRole in bipolar, esp rapid cycle

Role in early antipsychotic augmentationRole in early antipsychotic augmentation

Great for ongoing sleep problems... Is this protracted Great for ongoing sleep problems... Is this protracted withdrawal?withdrawal?

Is there a role in craving/relapse prevention?Is there a role in craving/relapse prevention?

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

Anticonvulsants in alcohol Anticonvulsants in alcohol withdrawalwithdrawal

Good evidence for carbamazepine, valproate and Good evidence for carbamazepine, valproate and growing for gabapentin and topiramategrowing for gabapentin and topiramate

May even be superior in terms of safety, ability May even be superior in terms of safety, ability for take home doses and in some studies, even for take home doses and in some studies, even anxiety/agitationanxiety/agitation

Have been shown effective in high dose BZP Have been shown effective in high dose BZP dependencedependence

Stay Cool and Stay Cool and Keep CalmKeep Calm