Alcohol and Co-Occurring Alcohol and Co-Occurring Psychiatric DisordersPsychiatric Disorders

Kathleen Brady, M.D., Ph.D.Kathleen Brady, M.D., Ph.D.

Medical University of South CarolinaMedical University of South Carolina

OverviewOverview• PrevalencePrevalence• Relationship between psychiatric and Relationship between psychiatric and

alcohol use disordersalcohol use disorders• Differential DiagnosisDifferential Diagnosis• Course of IllnessCourse of Illness• TreatmentTreatment

Specific Disorders of FocusSpecific Disorders of Focus

• Mood DisordersMood Disorders• Anxiety DisordersAnxiety Disorders• SchizophreniaSchizophrenia• Attention Deficit Hyperactivity DisorderAttention Deficit Hyperactivity Disorder

12-Month Odds of AUD and Mood/Anxiety12-Month Odds of AUD and Mood/Anxiety

Any AUD Alcohol Abuse Alcohol DependenceAny Mood Disorder 2.6% 1.3% 4.1%

Major Depression 2.3% 1.2% *3.7%Dysthymia 1.7% 0.8% 2.8%Mania 3.5% 1.4% *5.7%Hypomania 3.5% 1.7% *5.2%

Any Anxiety Disorder 1.7% 1.1% 2.6%Panic with Agoraphobia 2.5% 1.4% *3.6% without Agorphobia 2.0% 0.8% *3.4%Social Phobia 1.7% 0.9% 2.5%GAD 1.9% 0.9% *3.1%

Grant et al., 2004 Grant et al., 2004 Arch Gen PsychiatryArch Gen Psychiatry

• Substance-inducedSubstance-induced• Self-medicationSelf-medication• Common etiologyCommon etiology

– Common risk factorsCommon risk factors– Common neurobiologyCommon neurobiology

Alcohol Use Disorders and Psychiatric Alcohol Use Disorders and Psychiatric Disorders: Etiologic ConnectionsDisorders: Etiologic Connections

Diagnostic ConfusionDiagnostic Confusion

• Chronic alcohol use and withdrawal can Chronic alcohol use and withdrawal can mimic symptoms of many psychiatric mimic symptoms of many psychiatric disordersdisorders– Acute intoxication - mood symptomsAcute intoxication - mood symptoms– Withdrawal - anxiety and mood symptomsWithdrawal - anxiety and mood symptoms– Chronic use - delirium, cognitive changesChronic use - delirium, cognitive changes

Complex RelationshipComplex Relationship

• Relationship not unidirectionalRelationship not unidirectional

– Alcohol Use Disorders (AUD) increase risk for the Alcohol Use Disorders (AUD) increase risk for the development of psychiatric disorders - ? development of psychiatric disorders - ? adolescent use particularly problematicadolescent use particularly problematic

– Some psychiatric disorders increase risk for Some psychiatric disorders increase risk for development of AUDdevelopment of AUD

– Certain environmental conditions predispose to Certain environmental conditions predispose to both AUD and psychiatric disordersboth AUD and psychiatric disorders

– ? Shared genetic risk ? Shared genetic risk

Yale Family StudyYale Family Study

• Alcohol + anxiety increased risk for bothAlcohol + anxiety increased risk for both• Alcohol only = no increased anxietyAlcohol only = no increased anxiety• Anxiety only = increased alcoholAnxiety only = increased alcohol• Gender influenceGender influence• Shared etiologic factors:Shared etiologic factors:

– Genetic factors predisposing to bothGenetic factors predisposing to both– Environmental risk factorsEnvironmental risk factors

Merikangas KR, et al. Psychol Med. 1998; 28:773-788.

Two pathways for comorbidity suggested:Two pathways for comorbidity suggested:• Social anxiety disorder (SAD)Social anxiety disorder (SAD)

– Transmitted independentlyTransmitted independently– Precedes onset alcoholismPrecedes onset alcoholism– ? Self medication? Self medication

• Panic disorderPanic disorder– Shared diathesisShared diathesis– Nonsystematic order of onsetNonsystematic order of onset– ? Manifestations of underlying risk? Manifestations of underlying risk

Merikangas KR, et al. Psychol Med. 1998;28:773-788.

Familial Aggregation of Alcoholism and Familial Aggregation of Alcoholism and Anxiety DisordersAnxiety Disorders

• Abuse positively associated with a number of Abuse positively associated with a number of disordersdisorders

• Strongest relationship with alcohol/drug useStrongest relationship with alcohol/drug use

• More severe abuse increases riskMore severe abuse increases risk

• Not explained by background/familial factorsNot explained by background/familial factors

Kendler KS, et al. Arch Gen Psychiatry. 2000;57:953-959.

Childhood Sexual Abuse and Psychiatric Childhood Sexual Abuse and Psychiatric Disorders in WomenDisorders in Women

Screening and AssessmentScreening and Assessment

• Many screening tools availableMany screening tools available

• Diagnostic assessment requires more Diagnostic assessment requires more time/expertisetime/expertise

• Every individual with a psychiatric disorder Every individual with a psychiatric disorder should be screened for substance useshould be screened for substance use

• Every individual with a substance use Every individual with a substance use disorder should be screened for psychiatric disorder should be screened for psychiatric disorderdisorder

Diagnostic DifficultiesDiagnostic Difficulties

Diagnose if:Diagnose if:

• Symptoms clearly began before the onset Symptoms clearly began before the onset of substance use disorderof substance use disorder

• Symptoms persist during sustained Symptoms persist during sustained periods of abstinenceperiods of abstinence

• Shorter period of abstinence may be Shorter period of abstinence may be necessary to accurately diagnose some necessary to accurately diagnose some disordersdisorders

General Principles ofGeneral Principles of Differential Diagnosis Differential Diagnosis

• Order of onsetOrder of onset• Periods of abstinencePeriods of abstinence• Substance-induced symptoms abate Substance-induced symptoms abate

relatively quicklyrelatively quickly• Non-overlapping symptomsNon-overlapping symptoms• Family history positiveFamily history positive

APA Treatment GuidelinesAPA Treatment Guidelines

• When possible, delay treatment by 1-4 weeks When possible, delay treatment by 1-4 weeks to allow for the identification of transient to allow for the identification of transient substance-induced symptomssubstance-induced symptoms

• Earlier treatment if:Earlier treatment if:

– Severe symptomsSevere symptoms

– Symptoms precede substance use/prior Symptoms precede substance use/prior episodesepisodes

– Family history positiveFamily history positive

• Careful screening/diagnostic evaluationCareful screening/diagnostic evaluation

• Address psychiatric and AUD problems at same Address psychiatric and AUD problems at same timetime

• Use medication with least abuse potential and Use medication with least abuse potential and least toxicity should relapse occurleast toxicity should relapse occur

• Maximize the use of non-pharmacologic Maximize the use of non-pharmacologic treatmenttreatment

General Principles in theGeneral Principles in theTreatment of ComorbidityTreatment of Comorbidity

BenzodiazepinesBenzodiazepines

• Use beyond detoxification is controversialUse beyond detoxification is controversial

• Not absolute contraindicationNot absolute contraindication

• Difference in abuse potential within class:Difference in abuse potential within class:

– Diazepam/alprazolam Diazepam/alprazolam greater than greater than clonazepam/oxazepamclonazepam/oxazepam

• Important to maximize non-pharmacologic Important to maximize non-pharmacologic strategiesstrategies

• Cognitive-behavioral therapies efficacious in Cognitive-behavioral therapies efficacious in AUD’s and many psychiatric disordersAUD’s and many psychiatric disorders Enhance self-efficacyEnhance self-efficacy

Decrease helplessness/dependencyDecrease helplessness/dependency

Enhance coping strategiesEnhance coping strategies

PsychotherapyPsychotherapy

Synergy Between Pharmacotherapy Synergy Between Pharmacotherapy and Psychotherapyand Psychotherapy

• 95 methadone-maintained subjects95 methadone-maintained subjects• No main effect of sertralineNo main effect of sertraline• Significant impact of sertraline on Significant impact of sertraline on

depression in individuals with less depression in individuals with less adversity in environmentadversity in environment

Carpenter, K. M., et al., 2004. Drug Alcohol Depend, 74(2), 123-134.

MOOD DISORDERSMOOD DISORDERS

• Depressive DisordersDepressive Disorders

– Most common co-morbidityMost common co-morbidity

– Reflects prevalence in general populationReflects prevalence in general population

– Odds ratio approximately 2.0Odds ratio approximately 2.0• Bipolar DisorderBipolar Disorder

– Less prevalent in general population, but Less prevalent in general population, but higher percentage of BPAD have SUD’shigher percentage of BPAD have SUD’s

– Odds ratio 4.0-8.0Odds ratio 4.0-8.0

Prevalence Comorbid Mood Disorders Prevalence Comorbid Mood Disorders and AUDsand AUDs

Medication Treatment of Depression in Medication Treatment of Depression in Patients with Substance Use DisordersPatients with Substance Use Disorders

• Meta-analysisMeta-analysis• Prospective, double -blind, controlled Prospective, double -blind, controlled

trialstrials• 14 studies, 848 patients14 studies, 848 patients

– 5 with tricyclics5 with tricyclics– 7 with SSRI’s7 with SSRI’s– 2 other2 other

Nunes and Levin, JAMA, 2004

Nunes & Levin, JAMA,2004

Effect of Antidepressant Medication on Outcome of Effect of Antidepressant Medication on Outcome of Depression (Hamilton Depression Scale)Depression (Hamilton Depression Scale)

Nunes & Levin, JAMA, April 21, 2004

Effect of Antidepressant Medication on Effect of Antidepressant Medication on Outcome of Substance AbuseOutcome of Substance Abuse

ConclusionsConclusions

• Medications effective in treating depressionMedications effective in treating depression– High placebo response in some studies may High placebo response in some studies may

reflect inclusion of substance-induced depressionreflect inclusion of substance-induced depression– ? SSRI’s less effective? SSRI’s less effective

• Effective treatment of depression associated Effective treatment of depression associated with decreased substance usewith decreased substance use

Substance Use Disorder and Substance Use Disorder and Bipolar Disorder:Bipolar Disorder:

Multiple Levels of AssociationMultiple Levels of Association

• Phenomenological similaritiesPhenomenological similarities

– Impulsivity, irritability, etc.Impulsivity, irritability, etc.

• Neurobiological evidenceNeurobiological evidence

– Kindling, neuronal lossKindling, neuronal loss

• Pharmacological evidencePharmacological evidence

– Responsivity to anticonvulsant agentsResponsivity to anticonvulsant agents

Valproate Efficacy in Valproate Efficacy in Bipolar AlcoholicsBipolar Alcoholics

CC RR

Placebo + TauPlacebo + TauLithium & DR CounselingLithium & DR Counseling

Valproate + TauValproate + TauLithium & DR CounselingLithium & DR Counseling

Salloum, IM et al, Salloum, IM et al, Archives Gen Psych, 2005Archives Gen Psych, 2005

StabilizationStabilization

7-14 Days7-14 Days

NIAAA-FundedNIAAA-FundedInclusion:Inclusion:Acute bipolar episodeAcute bipolar episodeActive ETOH useActive ETOH use

Assessment q 2 weeksAssessment q 2 weeks

24 Weeks24 WeeksN: C=72N: C=72 R=59R=59 ITT=52 (88%)ITT=52 (88%) Completers=20Completers=20

Valproate vs. Placebo Valproate vs. Placebo Number of Drinks per Heavy Drinking Day Number of Drinks per Heavy Drinking Day

10.2

5.59

0

2

4

6

8

10

12

PP=0.02*=0.02*

ValproateValproaten=27n=27

PlacebPlaceboo

n=25n=25* Medication adherence as covariate in the Mixed Model* Medication adherence as covariate in the Mixed Model

Salloum, IM et al, Salloum, IM et al, Archives Gen Psychiatry, 2005Archives Gen Psychiatry, 2005

Num

ber

of

Dri

nks

N

um

ber

of

Dri

nks

Per

Heavy D

rinki

ng D

ay

Per

Heavy D

rinki

ng D

ay

ConclusionsConclusions

• Valproate treatment associated with Valproate treatment associated with significantly better drinking outcomes as significantly better drinking outcomes as compared to placebocompared to placebo

Moderate Alcohol Consumption and Moderate Alcohol Consumption and Illness Severity in Bipolar DisorderIllness Severity in Bipolar Disorder

• 148 bipolar patients with minimal 148 bipolar patients with minimal alcohol consumptionalcohol consumption– Drinks/week - 3.8 men; 1.2 womenDrinks/week - 3.8 men; 1.2 women

• Alcohol consumption associated with Alcohol consumption associated with lifetime manic/depressive episodes, lifetime manic/depressive episodes, emergency department visitsemergency department visits

• ? Increased sensitivity to impact of ? Increased sensitivity to impact of alcoholalcohol

Goldstein, B. I., et al (2006). Drugs, 66(9), 1229-1237

Psychotherapy in Substance-Using Psychotherapy in Substance-Using Bipolar PatientsBipolar Patients

• Cognitive behavioral therapies effective in both disordersCognitive behavioral therapies effective in both disorders

• Development of specific “integrated” therapyDevelopment of specific “integrated” therapy

– topics relevant to both disorderstopics relevant to both disorders

– relationship of disordersrelationship of disorders

• Integrated Group Therapy had better outcomesIntegrated Group Therapy had better outcomes

– ASI scoresASI scores

– % months abstinent% months abstinent

Weiss, R. D., et al. (2007). Am J Psychiatry, 164(1), 100-107.

ANXIETY DISORDERSANXIETY DISORDERS

12-Month Odds of Substance Use 12-Month Odds of Substance Use Disorders (SUDs) and Independent Disorders (SUDs) and Independent

Anxiety DisorderAnxiety Disorder

Any SUDAlcohol

DependenceDrug Dependence

Any anxiety disorder 1.9 2.6 6.2

Panic disorder

with agoraphobia

without agoraphobia

3.1

2.1

3.6

3.4

10.5

7.6

Social phobia

GAD

1.9

2.3

2.5

3.1

5.4

10.4

Grant BF, et al. Arch Gen Psychiatry. 2004;61:807-816.

GAD=generalized anxiety disorder.

Controlled Pharmacotherapy Trials Controlled Pharmacotherapy Trials Anxiety and AlcoholAnxiety and Alcohol

• 2 placebo-controlled trials positive using 2 placebo-controlled trials positive using buspirone for GAD/alcoholismbuspirone for GAD/alcoholism

• Small controlled trial of paroxetine in social Small controlled trial of paroxetine in social phobia/alcoholism positivephobia/alcoholism positive

• Controlled trial of sertraline in Post-traumatic Controlled trial of sertraline in Post-traumatic Stress Disorder (PTSD)/alcoholism robust Stress Disorder (PTSD)/alcoholism robust effects in subgroup of individuals with early effects in subgroup of individuals with early traumatrauma

Serotonin Reuptake InhibitorsSerotonin Reuptake Inhibitors

• Efficacious in treatment of Efficacious in treatment of anxiety disordersanxiety disorders

• Data in alcohol use disorders(AUDs) Data in alcohol use disorders(AUDs) alone inconsistentalone inconsistent

– Overall studies predominantly negative or Overall studies predominantly negative or show only modest improvementshow only modest improvement

– Subtyping by psychiatric comorbidity or Subtyping by psychiatric comorbidity or other features of illness shows promiseother features of illness shows promise

Generalized Anxiety Disorder Generalized Anxiety Disorder (GAD)(GAD)

• Strongly associated with alcohol dependence Strongly associated with alcohol dependence (OR 3.1)(OR 3.1)

• Much symptom overlap - diagnostic difficultyMuch symptom overlap - diagnostic difficulty• GAD in adolescents associated with GAD in adolescents associated with

progression to alcohol dependenceprogression to alcohol dependence• Sartor et al., 2007Sartor et al., 2007

• AUDs worsen course of illness in GADAUDs worsen course of illness in GAD• Bruce et al., 2005 Bruce et al., 2005

Sartor, et al. (2007). Addiction, 102(2), 216-225.

Bruce, et al. (2005). Am J Psychiatry, 162(6), 1179-1187.

Buspirone Treatment of Buspirone Treatment of Anxious AlcoholicsAnxious Alcoholics

• 61 anxious alcoholics61 anxious alcoholics• 12 week, placebo-controlled trial12 week, placebo-controlled trial• Relapse prevention therapyRelapse prevention therapy• Buspirone associated withBuspirone associated with

– Greater retentionGreater retention– Lower anxietyLower anxiety– Less consumptionLess consumption

Kranzler, et al. (1994). Arch Gen Psychiatry, 51(9), 720-731.

Panic DisorderPanic Disorder

• Risk of panic disorder elevated 2-4 fold in Risk of panic disorder elevated 2-4 fold in individuals with AUD’sindividuals with AUD’s

• Panic attacks can be associated with alcohol Panic attacks can be associated with alcohol withdrawal - substance-inducedwithdrawal - substance-induced

• Few treatment studies of co-occurringFew treatment studies of co-occurring– Cognitive behavioral therapy efficacious in Cognitive behavioral therapy efficacious in

uncomplicated panicuncomplicated panic– Selective serotonin reuptake inhibitors (SSRIs) Selective serotonin reuptake inhibitors (SSRIs)

efficacious in uncomplicated panicefficacious in uncomplicated panic

Cosci, et al. (2007). J Clin Psychiatry, 68(6), 874-880.

Social Anxiety Disorder (SAD)Social Anxiety Disorder (SAD)

• Key symptom, fear of scrutiny or social Key symptom, fear of scrutiny or social situations, has early onset, typically before situations, has early onset, typically before development of AUDdevelopment of AUD

• Lifetime prevalence of AUD in individuals with Lifetime prevalence of AUD in individuals with SAD is 48%SAD is 48%

• Prevalence of SAD in individuals with AUD Prevalence of SAD in individuals with AUD approximately 20%approximately 20%

Grant, et al. (2005). J Clin Psychiatry, 66(11), 1351-1361.

Paroxetine in Comorbid Paroxetine in Comorbid SAD and AlcoholismSAD and Alcoholism

• 15 men and women with social phobia and 15 men and women with social phobia and alcohol dependence or abusealcohol dependence or abuse

• Double-blind, placebo-controlledDouble-blind, placebo-controlled

• Paroxetine Paroxetine –– flexible dosing up to 60 mg/d flexible dosing up to 60 mg/d

• Brief motivational therapy for alcoholismBrief motivational therapy for alcoholism

Randall CL, et al. Depress Anxiety. 2001;14:255-262.

Paroxetine in Comorbid SAD and Paroxetine in Comorbid SAD and AlcoholismAlcoholism

Total Number of Drinks per Week

0

5

10

15

20

25

30

35

1 2 3 4 5 6 7 8

Paroxetine

Placebo

Weeks of Treatment

Ad

j ust

ed

Gro

u p M

ea n

s

Randall CL, et al. Depress Anxiety. 2001;14:255-262.

Treatment Studies: SAD/AUDTreatment Studies: SAD/AUD• Shade et al. (2005) Shade et al. (2005)

Alcoholism: Clinical Experimental ResearchAlcoholism: Clinical Experimental Research – 87 subjects with SAD plus AUD87 subjects with SAD plus AUD

– CBT plus optional fluvoxamine vs TAUCBT plus optional fluvoxamine vs TAU

– Combined treatment better than TAUCombined treatment better than TAU

• Randall CL, et al (2001) Randall CL, et al (2001) Alcoholism: Clinical Experimental ResearchAlcoholism: Clinical Experimental Research – CBT targeting both SAD and AUD symptoms vs CBT for CBT targeting both SAD and AUD symptoms vs CBT for

AUD onlyAUD only

– Combined treatment group had worse drinking outcomes - ? Combined treatment group had worse drinking outcomes - ? Exposure to social situations increased urge to drinkExposure to social situations increased urge to drink

MENMEN %% Odds RatioOdds RatioAlcohol Alcohol abuse/dependenceabuse/dependence 51.951.9 2.062.06

Drug Drug abuse/dependenceabuse/dependence 34.534.5 2.972.97

WOMENWOMENAlcohol Alcohol abuse/dependenceabuse/dependence 27.927.9 2.482.48

Drug Drug abuse/dependenceabuse/dependence 26.926.9 4.464.46

Kessler RC, et al. Arch Gen Psychiatry. 1995;52:1048-1060.

Comorbidity of PTSD and SUDsComorbidity of PTSD and SUDsNational Comorbidity StudyNational Comorbidity Study

• Characteristic symptoms that persist for Characteristic symptoms that persist for at least 1 month following traumaat least 1 month following trauma

• High incidence of traumatic life events High incidence of traumatic life events in individuals with AUD’sin individuals with AUD’s

• Treatment seeking individuals with Treatment seeking individuals with SUD’s : 36-50% lifetime PTSDSUD’s : 36-50% lifetime PTSD 25-42% current PTSD 25-42% current PTSD

Jacobsen LK, Am J Psychiatry, 158(8), 1184-1190.

Post Traumatic Stress Disorder Post Traumatic Stress Disorder (PTSD)(PTSD)

Co-Occurring PTSD/AUD Co-Occurring PTSD/AUD Treatment Treatment

• Exposure therapy demonstrated Exposure therapy demonstrated efficacy in PTSDefficacy in PTSD

• Reluctance to explore in individuals with Reluctance to explore in individuals with co-occurring AUD for fear of provoking co-occurring AUD for fear of provoking relapserelapse

• Preliminary studies in cocaine-Preliminary studies in cocaine-dependent individuals show promisedependent individuals show promise

Brady, et al. (2001) J Subst Abuse Treat, 21(1), 47-54.

PTSD Integrated Treatment: PTSD Integrated Treatment: Seeking SafetySeeking Safety

• 24 sessions in 12 weeks24 sessions in 12 weeks11

• Group therapy integrating CBT for SUDs Group therapy integrating CBT for SUDs and PTSDand PTSD11

• Emphasis of Seeking Safety :Emphasis of Seeking Safety :interpersonal relationships - no trauma interpersonal relationships - no trauma exposureexposure22

1. Hien DA, et al. Am J Psychiatry. 2004;161:1426-1432.2. Najavits LM. Seeking Safety. New York, NY: Guilford Publications; 2001.

PTSD and AlcoholismPTSD and AlcoholismTreatment With SertralineTreatment With Sertraline

• 12-week study12-week study

• Double-blind, placebo-controlled trialDouble-blind, placebo-controlled trial

• Weekly CBT targeting alcoholismWeekly CBT targeting alcoholism

• Measure alcohol and PTSD outcomesMeasure alcohol and PTSD outcomes

• 94 subjects with both PTSD and alcoholism94 subjects with both PTSD and alcoholism

– 43 women; 51 men43 women; 51 men

Brady KT, et al. Alcohol Clin Exp Res. 2005;29:343-352.

Cluster Analysis – SertralineCluster Analysis – Sertraline• 3 distinct clusters3 distinct clusters

– Cluster 1: Early-onset PTSD; later onset, Cluster 1: Early-onset PTSD; later onset, less severe alcoholism (N=14)less severe alcoholism (N=14)

– Cluster 2: Onset PTSD/alcohol relatively Cluster 2: Onset PTSD/alcohol relatively close; less severe alcohol dependence close; less severe alcohol dependence (N=53)(N=53)

– Cluster 3: Early onset, severe alcoholism; Cluster 3: Early onset, severe alcoholism; later-onset PTSD (N=27)later-onset PTSD (N=27)

Brady KT, et al. Alcohol Clin Exp Res. 2005;29:343-352.

Adjusted Mean Average Days Drinking Adjusted Mean Average Days Drinking Over Treatment PeriodOver Treatment Period

0.36

1.1

4.07

1.02 1.13

2.35

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Cluster 1 Cluster 2 Cluster 3

SertralinePlacebo

Cluster by group P=.068.Brady KT, et al. Alcohol Clin Exp Res. 2005;29:343-352.

Attention Deficit Hyperactivity Attention Deficit Hyperactivity Disorder - ADHDDisorder - ADHD

• Characterized by excessive activity, Characterized by excessive activity, inability to pay attention, impulsive inability to pay attention, impulsive behavior, poor organizational skillsbehavior, poor organizational skills

• Must appear in childhoodMust appear in childhood

• When unrecognized, associated with When unrecognized, associated with poor performance in school and workpoor performance in school and work

ADHD and ADHD and Substance Use DisordersSubstance Use Disorders

• No controlled trials in No controlled trials in pharmacotherapeutic strategies in pharmacotherapeutic strategies in substance userssubstance users

• Conventional wisdom: Avoid Conventional wisdom: Avoid psychostimulants, but not well studiedpsychostimulants, but not well studied

• Bupropion, venlafaxine, tricyclics, Bupropion, venlafaxine, tricyclics, clonidine may be usedclonidine may be used

Substance Use in Substance Use in SchizophreniaSchizophrenia

• Approximately 50% have lifetime SUD - Approximately 50% have lifetime SUD - alcohol most commonalcohol most common

• ? Reward dysfunction inherent in ? Reward dysfunction inherent in neuropathology, increased vulnerabilityneuropathology, increased vulnerability

• Some suggestion of better response to Some suggestion of better response to atypical antipsychoticsatypical antipsychotics

Naltrexone in Alcohol Naltrexone in Alcohol Dependence and SchizophreniaDependence and Schizophrenia• 31 subjects with co-occurring alcohol 31 subjects with co-occurring alcohol

dependence and schizophreniadependence and schizophrenia• Stabilized on antipsychotic medicationStabilized on antipsychotic medication• 12 weeks treatment with naltrexone (50 mg) 12 weeks treatment with naltrexone (50 mg)

vs placebovs placebo• Naltrexone group had fewer drinking days, Naltrexone group had fewer drinking days,

fewer heavy drinking days and less cravingfewer heavy drinking days and less craving» Petrakis et al., 2004

Disulfram and Naltrexone in Disulfram and Naltrexone in Comorbid PatientsComorbid Patients

• 254 patients with alcohol dependence plus 254 patients with alcohol dependence plus comorbid Axis I diagnosiscomorbid Axis I diagnosis

– 70% MDE; 42% PTSD; 19% Bipolar70% MDE; 42% PTSD; 19% Bipolar

• Disulfram and naltrexone alone and in Disulfram and naltrexone alone and in combinationcombination

• Active medication associated with longer Active medication associated with longer abstinence and less cravingabstinence and less craving

• No advantage of combination therapyNo advantage of combination therapy

Petrakis IL, et al. (2005). Biol Psychiatry, 57(10), 1128-1137.

Alcohol Use and Psychiatric Alcohol Use and Psychiatric Disorders: The FutureDisorders: The Future

• Exploration of agents that act on common Exploration of agents that act on common neural pathwaysneural pathways

• Exploration of medications targeting alcohol Exploration of medications targeting alcohol use disorders in individuals with psychiatric use disorders in individuals with psychiatric disorders disorders

• Development and exploration of Development and exploration of psychotherapeutic interventions specifically psychotherapeutic interventions specifically targeting co-occurring disorderstargeting co-occurring disorders

CONCLUSIONSCONCLUSIONS

• Substance use and psychiatric Substance use and psychiatric disorders disorders – commonly co-occurcommonly co-occur– etiologic connectionsetiologic connections– impact course of illnessimpact course of illness– impact treatment decisionsimpact treatment decisions