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Alcohol and Co-Occurring Psychiatric Disorders

Alcohol and Co-Occurring Psychiatric Disorders. Kathleen Brady, M.D., Ph.D. Medical University of South Carolina. Overview. Prevalence Relationship between psychiatric and alcohol use disorders Differential Diagnosis Course of Illness Treatment. Specific Disorders of Focus.

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Alcohol and Co-Occurring Psychiatric Disorders

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  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; 28:773-788.

  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. 1998;28:773-788.

  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. 2000;57:953-959.

  11. 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

  12. 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

  15. 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

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

  17. Psychotherapy • Important to maximize non-pharmacologic strategies • Cognitive-behavioral therapies efficacious in AUD’s and many psychiatric disorders • Enhance self-efficacy • Decrease helplessness/dependency • Enhance coping strategies

  18. 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.

  19. MOOD DISORDERS

  20. 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 SUD’s • Odds ratio 4.0-8.0

  21. 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 SSRI’s • 2 other Nunes and Levin, JAMA, 2004

  22. Effect of Antidepressant Medication on Outcome of Depression (Hamilton Depression Scale) Nunes & Levin, JAMA,2004

  23. Effect of Antidepressant Medication on Outcome of Substance Abuse Nunes & Levin, JAMA, April 21, 2004

  24. Conclusions • Medications effective in treating depression • High placebo response in some studies may reflect inclusion of substance-induced depression • ? SSRI’s less effective • Effective treatment of depression associated with decreased substance use

  25. Substance Use Disorder and Bipolar Disorder:Multiple Levels of Association • Phenomenological similarities • Impulsivity, irritability, etc. • Neurobiological evidence • Kindling, neuronal loss • Pharmacological evidence • Responsivity to anticonvulsant agents

  26. 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: C=72 R=59 ITT=52 (88%) Completers=20 Salloum, IM et al, Archives Gen Psych, 2005

  27. Valproate vs. Placebo Number of Drinks per Heavy Drinking Day P=0.02* Number of Drinks Per Heavy Drinking Day Placebo n=25 Valproate n=27 * Medication adherence as covariate in the Mixed Model Salloum, IM et al, Archives Gen Psychiatry, 2005

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

  29. 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

  30. 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.

  31. ANXIETY DISORDERS

  32. 12-Month Odds of Substance Use Disorders (SUDs) and Independent Anxiety Disorder GAD=generalized anxiety disorder. Grant BF, et al. Arch Gen Psychiatry. 2004;61:807-816.

  33. 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

  35. Sartor, et al. (2007). Addiction, 102(2), 216-225. • Bruce, et al. (2005). Am J Psychiatry, 162(6), 1179-1187. 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

  36. 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.

  37. Panic Disorder • Risk of panic disorder elevated 2-4 fold in individuals with AUD’s • 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.

  38. 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.

  39. 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. 2001;14:255-262.

  40. Paroxetine in Comorbid SAD and Alcoholism Adjusted Group Means Weeks of Treatment Randall CL, et al. Depress Anxiety. 2001;14:255-262.

  41. 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

  42. Comorbidity of PTSD and SUDsNational Comorbidity Study Kessler RC, et al. Arch Gen Psychiatry. 1995;52:1048-1060.

  43. 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 AUD’s • Treatment seeking individuals with SUD’s : 36-50% lifetime PTSD 25-42% current PTSD • Jacobsen LK, Am J Psychiatry, 158(8), 1184-1190.

  44. 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.

  45. 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. 2004;161:1426-1432.2. Najavits LM. Seeking Safety. New York, NY: Guilford Publications; 2001.

  46. 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. 2005;29:343-352.

  47. Cluster Analysis – Sertraline • 3 distinct clusters • Cluster 1: Early-onset PTSD; later onset, less severe alcoholism (N=14) • Cluster 2: Onset PTSD/alcohol relatively close; less severe alcohol dependence (N=53) • Cluster 3: Early onset, severe alcoholism; later-onset PTSD (N=27) Brady KT, et al. Alcohol Clin Exp Res. 2005;29:343-352.

  48. Adjusted Mean Average Days Drinking Over Treatment Period Cluster by group P=.068. Brady KT, et al. Alcohol Clin Exp Res. 2005;29:343-352.

  49. 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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