Objectives

1. Objectives The importance of identifying and treating bipolar disorder among patients with SUD�s as early as possible Ways to address and treat bipolar patients' SUDs � through psychosocial interventions, integrated care, or other treatment models Psychopharmacologic treatment of patients with bipolar disorder & SUD�s

2. Early Identification of Bipolar Disorderin Substance Use Disorder (BD-SUD) 7- to10-year lag diagnosing BD in the general population Clinical Barriers: Substances as triggers ? more episodes Episodes as triggers ? substance use Diagnostic dilemmas and dismissals: �It�s all due to�substances.� �It�s all due to�bipolar disorder.�

3. Early Identification in BD-SUD System Barriers Financing Healthcare Organization Training and Culture SAMHSA�s No Wrong Door Policy VHA Advantage: There is no wrong door� �theoretically�

4. Principles of BD-SUD Treatment Parallel (not serial) treatment Goals of Parallel Treatment Get substances �off the table� for dealing with illness and life Stabilize symptoms to allow participation in substance treatment

5. Principles of BD-SUD Treatment Look for and seek out complications Depression Mania Subtle Psychosis Anxiety Perseverance: �Sometimes the 17th time�s a charm�� Collaboration beats confrontation Bauer MS, Altshuler L, Evans DR, et al. VA Cooperative Study #430 Team. Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder. J Affective Disorders 2005;85:301-15. Bauer MS, Altshuler L, Evans DR, et al. VA Cooperative Study #430 Team. Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder. J Affective Disorders 2005;85:301-15.

8. Examples of Collaborative Interventions for BD-SUD Motivational Interviewing Miller & Rollnick and others Integrated Group Therapy Weiss Life Goals Program & Collaborative Chronic Care VA Cooperative Study #430 Bauer MS, Williford WO, Dawson EE. Principles of effectiveness trials and their Implementation in VA Cooperative Study #439: �Reducing the efficacy-effectiveness Gap in Bipolar Disorder.� J Affect Disorder 2001; 67: 61-78. Miller WR, Yahne CE, Moyers TB, Martinez J, Pirritano M A randomized trial of methods to help clinicians learn motivational interviewing. J of consulting and clinical psychology. 2004; 72:1050-62. Miller WR, Yahne CE, Tonigan JS Motivational interviewing in drug abuse services: a randomized trial. Journal of consulting and clinical psychology. 2003; 71:754-63. Miller W, Rollnick S. Motivational interviewing: preparing people to change. New York: Guilford Press, 2002. Salloum IM and Thase, ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disorders 2000; 2:269-280. Weiss RD, Najavitis LM. Overview of treatment modalities for dual diagnosis patients: pharmacotherapy, psychotherapy and 12-step programs. In: Kranzler H, Rounsaville H, Bruce J, eds. Dual Diagnosis and Treatment: Substance Abuse and Comorbid Medical and Psychiatric Disorders, viii ed. New York: Marcel Dekker, 1998;107-137. Weiss RD, Greenfield SF, Najavitis LM, et al. Medication compliance among patients with bipolar disorder and substance use disorders. J Clin Psychiatr 1998; 59: 172-74. Weiss RD, Najavitis LM, Greenfeld SF, A relapse prevention group for patients with bipolar and substance use disorders. J Subst Abuse Treat. 1999; 16: 47-54. Bauer MS, Williford WO, Dawson EE. Principles of effectiveness trials and their Implementation in VA Cooperative Study #439: �Reducing the efficacy-effectiveness Gap in Bipolar Disorder.� J Affect Disorder 2001; 67: 61-78. Miller WR, Yahne CE, Moyers TB, Martinez J, Pirritano M A randomized trial of methods to help clinicians learn motivational interviewing. J of consulting and clinical psychology. 2004; 72:1050-62. Miller WR, Yahne CE, Tonigan JS Motivational interviewing in drug abuse services: a randomized trial. Journal of consulting and clinical psychology. 2003; 71:754-63. Miller W, Rollnick S. Motivational interviewing: preparing people to change. New York: Guilford Press, 2002. Salloum IM and Thase, ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disorders 2000; 2:269-280. Weiss RD, Najavitis LM. Overview of treatment modalities for dual diagnosis patients: pharmacotherapy, psychotherapy and 12-step programs. In: Kranzler H, Rounsaville H, Bruce J, eds. Dual Diagnosis and Treatment: Substance Abuse and Comorbid Medical and Psychiatric Disorders, viii ed. New York: Marcel Dekker, 1998;107-137. Weiss RD, Greenfield SF, Najavitis LM, et al. Medication compliance among patients with bipolar disorder and substance use disorders. J Clin Psychiatr 1998; 59: 172-74. Weiss RD, Najavitis LM, Greenfeld SF, A relapse prevention group for patients with bipolar and substance use disorders. J Subst Abuse Treat. 1999; 16: 47-54.

9. Purposes of Psychosocial Interventions Supplement (not replace) pharmacologic treatment Enhance illness management skills Address independent determinants of disease outcome (stressors, comorbidities) Enhance social role function and quality of life Reduce depression

10. Types of PsychosocialInterventions Psychotherapies: Add-on Integrated Treatment Models: Multimodal Packages

11. Types of Individual Psychotherapy Psychodynamic (Past life events) Supportive (Current life events) Interpersonal (Social relationships) Cognitive Behavioral (Thought habits) Social Rhythm (Stabilizing social rhythms) Psychoeducation (Knowledge and coping strategies)

12. Group Psychotherapy Mutual support Shared experiences Work on personal goals Stigma reduction

13. Other Psychotherapy Family Therapy Challenges in relationships between family members-conflict resolution Increase supportive family relationships Self-help Groups

14. Integrated Treatment Models Intensive Case Management Recovery-Oriented Programs Collaborative Chronic Care Models

15. Intensive Case Management Involves mobile community outreach, rehabilitative services via provider teams Examples: ACT, MHICM Effective for SMI and co-occurring SUD High start-up costs impede dissemination into routine care ACT=Assertive Community Treatment MHICM=Mental Health Intensive Case Management SMI= Serious Mental IllnessACT=Assertive Community Treatment MHICM=Mental Health Intensive Case Management SMI= Serious Mental Illness

16. Recovery-Oriented Programs �Mental health recovery is a journey of healing and transformation enabling a person with a mental health problem to live a meaningful life in a community of his or her choice while striving to achieve his or her full potential.� SAMHSA 2005 Include peer support, vocational training, family involvement, and other services United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/United States Department of Health and Human Services. Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/

17. Collaborative Chronic Care Models Clinic-based tools to promote self-management and continuity of care for chronic illnesses VA CSP #430 Self-management (Life Goals Program - group sessions) Delivery system/clinical information system redesign Decision support (Clinical Practice Guidelines)

18. VA CSP #430 Chronic Care Model for Bipolar Disorder

19. Life Goals Program Education, group interaction and support Personal symptom profile(s), warning signs Triggers and coping resources Personal cost-benefit analysis Action plan / personal care plan Destigmatization

20. Responding to Depression/Stress by Drinking Alcohol I can finally sleep I don�t get panic attacks I don�t feel so down It gets me out of the house, and when I socialize, I forget my troubles My wife gets mad at me Sometimes, it makes me not care & feel like killing myself I feel terrible the next morning

21. Medications for the Management of Bipolar Disorder Lithium Anticonvulsants Antipsychotics Antidepressants Benzodiazepines

22. Medications for the SUD Treatment Acamprosate Amantadine Buprenorphine/Naloxone Bupropion

23. Medications for SUD Treatment Disulfiram Methadone Naltrexone Nicotine replacement

24. Inadequacy of Treatment Only 59% of patients with BD-SUD were on adequate mood stabilizing regimens Only 0.4% were receiving substance abuse-specific medications Simon, NM, Otto, MW, Weiss, RD et al. for STEP-BD Investigators. Pharmacotherapy for Bipolar Disorder and Comorbid Conditions: Baseline Data From STEP-BD. J Clin Psychopharmacol. 2004; 24: 512-520.Simon, NM, Otto, MW, Weiss, RD et al. for STEP-BD Investigators. Pharmacotherapy for Bipolar Disorder and Comorbid Conditions: Baseline Data From STEP-BD. J Clin Psychopharmacol. 2004; 24: 512-520.

25. Reasons for Non-Response Non-adherence Inadequate dosing Relapse to substance use Incorrect diagnosis/indication Drug interactions Adverse drug reactions Alcohol + psych meds Disulfiram-acetaldehyde (death?), MAOI-tyramine (hypertensive crisis), TCA- acute, inhibit metabolism; chronic, induce metabolism Neuroleptics- CNS (akathisia, dystonia) Barbs � enzyme induction, resp depression Bz�s and opiates � resp depression Stimulants � exacerbation of psychosis Nicotine � enzyme induction; stop smoking � enzyme revert to nl and levels may rise Alcohol + psych meds Disulfiram-acetaldehyde (death?), MAOI-tyramine (hypertensive crisis), TCA- acute, inhibit metabolism; chronic, induce metabolism Neuroleptics- CNS (akathisia, dystonia) Barbs � enzyme induction, resp depression Bz�s and opiates � resp depression Stimulants � exacerbation of psychosis Nicotine � enzyme induction; stop smoking � enzyme revert to nl and levels may rise

26. Strength of Evidence Study design Randomized controlled trials Open-label trials Retrospective studies Case series/reports Outcome measures

27. Lithium 2 open-label 12 week studies Cocaine dependent patients N=16 3/16 decreased craving N=10 5/10 decreased craving 3/10 cocaine free x 3 wks Gawin FH, Kleber HD. Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate. Arch Gen Psychiatry. 1984;41:903-9.Gawin FH, Kleber HD. Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate. Arch Gen Psychiatry. 1984;41:903-9.

28. Lithium 6 wk, Randomized, Double Blind, Placebo Controlled, Parallel group Adolescent outpts (BD I, II or MD; N=25) Alcohol, marijuana, inhalant, cough syrup Percentage of positive urine drug screens decreased in the lithium group (p=0.028) Geller B, Cooper TB, Sun K, et al. Double-blind and Placebo-controlled Study of Lithium for Adolescent Bipolar Disorders With Secondary Substance Dependency. Acad Child & Adolesc Psychiatry. 1998; 37:171-178.Geller B, Cooper TB, Sun K, et al. Double-blind and Placebo-controlled Study of Lithium for Adolescent Bipolar Disorders With Secondary Substance Dependency. Acad Child & Adolesc Psychiatry. 1998; 37:171-178.

29. Valproate 24 wk, open-label study in alcohol, cocaine or SUD outpts (N=9) Decreased days of substance used (p<0.005) Brady KT, Sonne SL, Anton R et al. Valproate in the Treatment of Acute Bipolar Affective Episodes Complicated by Substance Abuse. A Pilot Study. et al J Clin Psychiatry 1995 Brady KT, Sonne SL, Anton R et al. Valproate in the Treatment of Acute Bipolar Affective Episodes Complicated by Substance Abuse. A Pilot Study. et al J Clin Psychiatry 1995

30. Valproate 24 wk, RCT, in BD I pts with alcohol dependence receiving lithium (N=59) Fewer heavy drinking days (p=0.02) Higher serum concentration correlated with improved alcohol use outcomes No significant changes in mood symptoms Salloum IM, Cornelius JR, Daley DC et al. Efficacy of Valproate Maintenance in Patients with Bipolar Disorder and Alcoholism. Arch Gen Psychiatry 2005;62:37-45. Salloum IM, Cornelius JR, Daley DC et al. Efficacy of Valproate Maintenance in Patients with Bipolar Disorder and Alcoholism. Arch Gen Psychiatry 2005;62:37-45.

31. Lithium and Valproate 24 wk, open-label, in 56 with alcohol, cannabis, and/or cocaine dependent outpts 14 pts met DSM-IV criteria for full remission of alcohol or drug use disorder after 6 months Calabrese JR, Shelton MD, Bowden CL et al. Bipolar Rapid Cycling: Focus on Depression as Its Hallmark. J Clin Psychiatry 2001;62:34-41.Calabrese JR, Shelton MD, Bowden CL et al. Bipolar Rapid Cycling: Focus on Depression as Its Hallmark. J Clin Psychiatry 2001;62:34-41.

32. Carbamazepine 12 wk, placebo controlled, outpts with cocaine dependence (N=139) N=57 cocaine dependent with mood d/o N=82 without mood d/o Decreased drug craving Significantly longer time to first cocaine use in pts with mood disorders No difference in cocaine use in pts without mood disorders Brady KT, Sonne SC, Malcolm RJ, et al. Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder. Exp Clin Psychopharmacol. 2002: 10:276-85.Brady KT, Sonne SC, Malcolm RJ, et al. Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder. Exp Clin Psychopharmacol. 2002: 10:276-85.

33. Gabapentin 43 pts with bipolar disorder resistant to standard treatment received gabapentin adjunctively for 8 wks (case series) 18/43 (42%) responded Alcohol abuse was associated with positive response Perugi G, Toni C, Frare F et al. Effectiveness of Adjunctive Gabapentin in Resistant Bipolar Disorder: Is It Due to Anxious-Alcohol Abuse Comorbidity? J Clin Psychopharmacol 2002;22:584-591.Perugi G, Toni C, Frare F et al. Effectiveness of Adjunctive Gabapentin in Resistant Bipolar Disorder: Is It Due to Anxious-Alcohol Abuse Comorbidity? J Clin Psychopharmacol 2002;22:584-591.

34. Lamotrigine 12 wk, open-label, in 30 cocaine dependent outpts Decreased craving and NS decrease days of use and money spent on cocaine No change in positive urine drug screens Brown ES, Jeffress J, Liggin JEM et al, Switching Outpatients with Biplar or Schizoaffective Disorders and Substance Abuse from their current antipsychotic to Ariprazole. J Clin Psychiatry 2003 Brown ES, Jeffress J, Liggin JEM et al, Switching Outpatients with Biplar or Schizoaffective Disorders and Substance Abuse from their current antipsychotic to Ariprazole. J Clin Psychiatry 2003

35. Aripiprazole 20 antipsychotic-treated pts with bipolar or schizoaffective d/o and substance abuse switched to open-label aripiprazole for 12 wks 17 with alcohol dependence showed a reduction in dollars spent (p=0.042) and craving (p=0.003) 9 with cocaine-related d/o showed a reduction in craving (p=0.014) but not in use Brown ES, Jeffress J, Liggin JDM et al, Switching Outpatients with Biplar or Schizoaffective Disorders and Substance Abuse from their current antipsychotic to Aripiprazole. J Clin Psychiatry 2005; 66:767-760. Brown ES, Jeffress J, Liggin JDM et al, Switching Outpatients with Biplar or Schizoaffective Disorders and Substance Abuse from their current antipsychotic to Aripiprazole. J Clin Psychiatry 2005; 66:767-760.

36. Quetiapine 12 wk, open-label, outpts with cocaine dependence (N=17) Decreased craving and NS decrease in days of cocaine use and money spent on cocaine Slight increase in positive urine drug screens Subset with alcohol use (N=14) Decrease in craving Decrease in days of alcohol use/wk but not drinks/wk Brown ES, Mejtek VA, Perantie DC et al. Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord 2002;4:407-11. Brown ES, Mejtek VA, Perantie DC et al. Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord 2002;4:407-11.

37. Ongoing RCTs Quetiapine vs risperidone in bipolar disorder with stimulant dependence Divalproex ER vs risperidone in BD-SUD www.clinicaltrials.govwww.clinicaltrials.gov

38. Summary of Medications for Management of Bipolar Disorder Few randomized controlled trials Most data with valproate and carbamazepine Trials are short duration (no long term trials) Small samples Comorbid substances vary in studies Definition of response Further research is needed

39. Use Caution When Treating BD-SUD Impulsivity/Toxicity Tricyclics MAOIs Abuse Opiates Stimulants Barbiturates BZDs

40. VANTS Call May 30, 2006 2:00 pm Eastern 1-800-767-1750 Access Code 14945