Alcohol and Co-Occurring Psychiatric Disorders

1
Alcohol and Co-Occurring Psychiatric Disorders

• Kathleen Brady, M.D., Ph.D.
• Medical University of South Carolina

2
Overview

• Prevalence
• Relationship between psychiatric and alcohol use
  disorders
• Differential Diagnosis
• Course of Illness
• Treatment

3
Specific Disorders of Focus

• Mood Disorders
• Anxiety Disorders
• Schizophrenia
• Attention Deficit Hyperactivity Disorder

4
12-Month Odds of AUD and Mood/Anxiety
Grant et al., 2004 Arch Gen Psychiatry
5
Alcohol Use Disorders and Psychiatric Disorders
Etiologic Connections

• Substance-induced
• Self-medication
• Common etiology
• Common risk factors
• Common neurobiology

6
Diagnostic Confusion

• Chronic alcohol use and withdrawal can mimic
  symptoms of many psychiatric disorders
• Acute intoxication - mood symptoms
• Withdrawal - anxiety and mood symptoms
• Chronic use - delirium, cognitive changes

7
Complex Relationship

• Relationship not unidirectional
• Alcohol Use Disorders (AUD) increase risk for the
  development of psychiatric disorders - ?
  adolescent use particularly problematic
• Some psychiatric disorders increase risk for
  development of AUD
• Certain environmental conditions predispose to
  both AUD and psychiatric disorders
• ? Shared genetic risk

8
Yale Family Study

• Alcohol anxiety increased risk for both
• Alcohol only no increased anxiety
• Anxiety only increased alcohol
• Gender influence
• Shared etiologic factors
• Genetic factors predisposing to both
• Environmental risk factors

Merikangas KR, et al. Psychol Med. 1998
28773-788.
9
Familial Aggregation of Alcoholism and Anxiety
Disorders

• Two pathways for comorbidity suggested
• Social anxiety disorder (SAD)
• Transmitted independently
• Precedes onset alcoholism
• ? Self medication
• Panic disorder
• Shared diathesis
• Nonsystematic order of onset
• ? Manifestations of underlying risk

Merikangas KR, et al. Psychol Med.
199828773-788.
10
Childhood Sexual Abuse and Psychiatric Disorders
in Women

• Abuse positively associated with a number of
  disorders
• Strongest relationship with alcohol/drug use
• More severe abuse increases risk
• Not explained by background/familial factors

Kendler KS, et al. Arch Gen Psychiatry.
200057953-959.
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Screening and Assessment

• Many screening tools available
• Diagnostic assessment requires more
  time/expertise
• Every individual with a psychiatric disorder
  should be screened for substance use
• Every individual with a substance use disorder
  should be screened for psychiatric disorder

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Diagnostic Difficulties

• Diagnose if
• Symptoms clearly began before the onset of
  substance use disorder
• Symptoms persist during sustained periods of
  abstinence
• Shorter period of abstinence may be necessary to
  accurately diagnose some disorders

13
General Principles of Differential Diagnosis

• Order of onset
• Periods of abstinence
• Substance-induced symptoms abate relatively
  quickly
• Non-overlapping symptoms
• Family history positive

14
APA Treatment Guidelines

• When possible, delay treatment by 1-4 weeks to
  allow for the identification of transient
  substance-induced symptoms
• Earlier treatment if
• Severe symptoms
• Symptoms precede substance use/prior episodes
• Family history positive

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General Principles in theTreatment of Comorbidity

• Careful screening/diagnostic evaluation
• Address psychiatric and AUD problems at same time
• Use medication with least abuse potential and
  least toxicity should relapse occur
• Maximize the use of non-pharmacologic treatment

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Benzodiazepines

• Use beyond detoxification is controversial
• Not absolute contraindication
• Difference in abuse potential within class
• Diazepam/alprazolam greater than
  clonazepam/oxazepam

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Psychotherapy

• Important to maximize non-pharmacologic
  strategies
• Cognitive-behavioral therapies efficacious in
  AUDs and many psychiatric disorders
• Enhance self-efficacy
• Decrease helplessness/dependency
• Enhance coping strategies

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Synergy Between Pharmacotherapy and Psychotherapy

• 95 methadone-maintained subjects
• No main effect of sertraline
• Significant impact of sertraline on depression in
  individuals with less adversity in environment

Carpenter, K. M., et al., 2004. Drug Alcohol
Depend, 74(2), 123-134.
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MOOD DISORDERS
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Prevalence Comorbid Mood Disorders and AUDs

• Depressive Disorders
• Most common co-morbidity
• Reflects prevalence in general population
• Odds ratio approximately 2.0
• Bipolar Disorder
• Less prevalent in general population, but higher
  percentage of BPAD have SUDs
• Odds ratio 4.0-8.0

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Medication Treatment of Depression in Patients
with Substance Use Disorders

• Meta-analysis
• Prospective, double -blind, controlled trials
• 14 studies, 848 patients
• 5 with tricyclics
• 7 with SSRIs
• 2 other

Nunes and Levin, JAMA, 2004
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Effect of Antidepressant Medication on Outcome of
Depression (Hamilton Depression Scale)
Nunes Levin, JAMA,2004
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Effect of Antidepressant Medication on Outcome of
Substance Abuse
Nunes Levin, JAMA, April 21, 2004
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Conclusions

• Medications effective in treating depression
• High placebo response in some studies may reflect
  inclusion of substance-induced depression
• ? SSRIs less effective
• Effective treatment of depression associated with
  decreased substance use

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Substance Use Disorder and Bipolar
DisorderMultiple Levels of Association

• Phenomenological similarities
• Impulsivity, irritability, etc.
• Neurobiological evidence
• Kindling, neuronal loss
• Pharmacological evidence
• Responsivity to anticonvulsant agents

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Valproate Efficacy in Bipolar Alcoholics
NIAAA-Funded
Inclusion Acute bipolar episode Active ETOH use
Placebo Tau Lithium DR Counseling
C
R
Valproate Tau Lithium DR Counseling
Stabilization
Assessment q 2 weeks
7-14 Days
24 Weeks
N C72 R59 ITT52 (88) Completers20
Salloum, IM et al, Archives Gen Psych, 2005
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Valproate vs. Placebo Number of Drinks per
Heavy Drinking Day
P0.02
Number of Drinks Per Heavy Drinking Day
Valproate n27
Placebo n25
Medication adherence as covariate in the Mixed
Model
Salloum, IM et al, Archives Gen Psychiatry, 2005
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Conclusions

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

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Moderate Alcohol Consumption and Illness Severity
in Bipolar Disorder

• 148 bipolar patients with minimal alcohol
  consumption
• Drinks/week - 3.8 men 1.2 women
• Alcohol consumption associated with lifetime
  manic/depressive episodes, emergency department
  visits
• ? Increased sensitivity to impact of alcohol

Goldstein, B. I., et al (2006). Drugs, 66(9),
1229-1237
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Psychotherapy in Substance-Using Bipolar Patients

• Cognitive behavioral therapies effective in both
  disorders
• Development of specific integrated therapy
• topics relevant to both disorders
• relationship of disorders
• Integrated Group Therapy had better outcomes
• ASI scores
• months abstinent

Weiss, R. D., et al. (2007). Am J Psychiatry,
164(1), 100-107.
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ANXIETY DISORDERS
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12-Month Odds of Substance Use Disorders (SUDs)
and Independent Anxiety Disorder
GADgeneralized anxiety disorder.
Grant BF, et al. Arch Gen Psychiatry.
200461807-816.
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Controlled Pharmacotherapy Trials Anxiety and
Alcohol

• 2 placebo-controlled trials positive using
  buspirone for GAD/alcoholism
• Small controlled trial of paroxetine in social
  phobia/alcoholism positive
• Controlled trial of sertraline in Post-traumatic
  Stress Disorder (PTSD)/alcoholism robust effects
  in subgroup of individuals with early trauma

34
Serotonin Reuptake Inhibitors

• Efficacious in treatment of anxiety disorders
• Data in alcohol use disorders(AUDs) alone
  inconsistent
• Overall studies predominantly negative or show
  only modest improvement
• Subtyping by psychiatric comorbidity or other
  features of illness shows promise

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Generalized Anxiety Disorder (GAD)

• Strongly associated with alcohol dependence (OR
  3.1)
• Much symptom overlap - diagnostic difficulty
• GAD in adolescents associated with progression to
  alcohol dependence
• Sartor et al., 2007
• AUDs worsen course of illness in GAD
• Bruce et al., 2005

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Buspirone Treatment of Anxious Alcoholics

• 61 anxious alcoholics
• 12 week, placebo-controlled trial
• Relapse prevention therapy
• Buspirone associated with
• Greater retention
• Lower anxiety
• Less consumption

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

• Risk of panic disorder elevated 2-4 fold in
  individuals with AUDs
• Panic attacks can be associated with alcohol
  withdrawal - substance-induced
• Few treatment studies of co-occurring
• Cognitive behavioral therapy efficacious in
  uncomplicated panic
• Selective serotonin reuptake inhibitors (SSRIs)
  efficacious in uncomplicated panic

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

• Key symptom, fear of scrutiny or social
  situations, has early onset, typically before
  development of AUD
• Lifetime prevalence of AUD in individuals with
  SAD is 48
• Prevalence of SAD in individuals with AUD
  approximately 20

Grant, et al. (2005). J Clin Psychiatry, 66(11),
1351-1361.
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Paroxetine in Comorbid SAD and Alcoholism

• 15 men and women with social phobia and alcohol
  dependence or abuse
• Double-blind, placebo-controlled
• Paroxetine flexible dosing up to 60 mg/d
• Brief motivational therapy for alcoholism

Randall CL, et al. Depress Anxiety.
200114255-262.
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Paroxetine in Comorbid SAD and Alcoholism
Adjusted Group Means
Weeks of Treatment
Randall CL, et al. Depress Anxiety.
200114255-262.
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Treatment Studies SAD/AUD

• Shade et al. (2005) Alcoholism Clinical
  Experimental Research
• 87 subjects with SAD plus AUD
• CBT plus optional fluvoxamine vs TAU
• Combined treatment better than TAU
• Randall CL, et al (2001) Alcoholism Clinical
  Experimental Research
• CBT targeting both SAD and AUD symptoms vs CBT
  for AUD only
• Combined treatment group had worse drinking
  outcomes - ? Exposure to social situations
  increased urge to drink

43
Comorbidity of PTSD and SUDsNational Comorbidity
Study
Kessler RC, et al. Arch Gen Psychiatry.
1995521048-1060.
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Post Traumatic Stress Disorder (PTSD)

• Characteristic symptoms that persist for at least
  1 month following trauma
• High incidence of traumatic life events in
  individuals with AUDs
• Treatment seeking individuals with SUDs
  36-50 lifetime PTSD 25-42 current
  PTSD

Jacobsen LK, Am J Psychiatry, 158(8), 1184-1190.
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Co-Occurring PTSD/AUD Treatment

• Exposure therapy demonstrated efficacy in PTSD
• Reluctance to explore in individuals with
  co-occurring AUD for fear of provoking relapse
• Preliminary studies in cocaine-dependent
  individuals show promise

Brady, et al. (2001) J Subst Abuse Treat, 21(1),
47-54.
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PTSD Integrated Treatment Seeking Safety

• 24 sessions in 12 weeks1
• Group therapy integrating CBT for SUDs and PTSD1
• Emphasis of Seeking Safety interpersonal
  relationships - no trauma exposure2

1. Hien DA, et al. Am J Psychiatry.
20041611426-1432.2. Najavits LM. Seeking
Safety. New York, NY Guilford Publications 2001.
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PTSD and AlcoholismTreatment With Sertraline

• 12-week study
• Double-blind, placebo-controlled trial
• Weekly CBT targeting alcoholism
• Measure alcohol and PTSD outcomes
• 94 subjects with both PTSD and alcoholism
• 43 women 51 men

Brady KT, et al. Alcohol Clin Exp Res.
200529343-352.
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Cluster Analysis Sertraline

• 3 distinct clusters
• Cluster 1 Early-onset PTSD later onset, less
  severe alcoholism (N14)
• Cluster 2 Onset PTSD/alcohol relatively close
  less severe alcohol dependence (N53)
• Cluster 3 Early onset, severe alcoholism
  later-onset PTSD (N27)

Brady KT, et al. Alcohol Clin Exp Res.
200529343-352.
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Adjusted Mean Average Days Drinking Over
Treatment Period
Cluster by group P.068.
Brady KT, et al. Alcohol Clin Exp Res.
200529343-352.
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Attention Deficit Hyperactivity Disorder - ADHD

• Characterized by excessive activity, inability to
  pay attention, impulsive behavior, poor
  organizational skills
• Must appear in childhood
• When unrecognized, associated with poor
  performance in school and work

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ADHD and Substance Use Disorders

• No controlled trials in pharmacotherapeutic
  strategies in substance users
• Conventional wisdom Avoid psychostimulants, but
  not well studied
• Bupropion, venlafaxine, tricyclics, clonidine may
  be used

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Substance Use in Schizophrenia

• Approximately 50 have lifetime SUD - alcohol
  most common
• ? Reward dysfunction inherent in neuropathology,
  increased vulnerability
• Some suggestion of better response to atypical
  antipsychotics

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Naltrexone in Alcohol Dependence and Schizophrenia

• 31 subjects with co-occurring alcohol dependence
  and schizophrenia
• Stabilized on antipsychotic medication
• 12 weeks treatment with naltrexone (50 mg) vs
  placebo
• Naltrexone group had fewer drinking days, fewer
  heavy drinking days and less craving
• Petrakis et al., 2004

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Disulfram and Naltrexone in Comorbid Patients

• 254 patients with alcohol dependence plus
  comorbid Axis I diagnosis
• 70 MDE 42 PTSD 19 Bipolar
• Disulfram and naltrexone alone and in combination
• Active medication associated with longer
  abstinence and less craving
• No advantage of combination therapy

Petrakis IL, et al. (2005). Biol Psychiatry,
57(10), 1128-1137.
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Alcohol Use and Psychiatric Disorders The Future

• Exploration of agents that act on common neural
  pathways
• Exploration of medications targeting alcohol use
  disorders in individuals with psychiatric
  disorders
• Development and exploration of psychotherapeutic
  interventions specifically targeting co-occurring
  disorders

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CONCLUSIONS

• Substance use and psychiatric disorders
• commonly co-occur
• etiologic connections
• impact course of illness
• impact treatment decisions