1. John Tsuang, M.D., M.S. Associate Clinical Professor Department of Psychiatry, University of California Los Angeles Director of Dual Diagnostic Treatment Program Harbor - UCLA Medical Center Johntsuang@yahoo.com

2. Outline n Prevalence n Psychiatric symptoms and abstinence n Diagnosis of dual diagnosis patients n Pharmacological Treatment

5. Prevalence of dual diagnosis patients

6. Prevalence of Dual Diagnosis Epidemiological Catchment Area (ECA) Study N= 20291 n lifetime prevalence rates for alcohol, drug, and mental disorders 32.7% n lifetime prevalence rates for any non-substance abuse mental disorders22.5% n Alcohol disorders13.5% n Other drug disorders6.1% *Regier, AJ Psych 1990

7. Mental Disorder Patients: n Life prevalence of additive disorders 29%(OR = 2.7) n Alcohol disorders 22%(OR = 2.3) n Other drug disorders 15%(OR = 4.5) n 45%-70% abuse alcohol or drugs

8. Affective Disorders (8.3%) Substance Abuse Disorders 32% (OR =2.6) Alcohol 22% Drug 19%

9. Subtypes of Affective Disorders Bipolar I Disorder Substance Abuse Disorders 61% (OR = 7.9) Alcohol 46% Drug 40% Unipolar major depression Substance Abuse Disorders 27% (OR = 1.7) Alcohol 16% Drug 18%

10. Anxiety Disorder (14.6%) Substance Abuse Disorders 23.7% (OR = 1.7) Alcohol 18% Drug 12%

11. Subtypes of Anxiety Disorders Panic Disorder (10.6%) Substance Abuse Disorders 35.8% (OR = 2.9) Obsessive-Compulsive Disorder(2.5%) Substance Abuse Disorders 32.8% (OR = 2.5) Phobia (12.6%) Substance Abuse Disorders 22.9% (OR = 1.6)

12. Schizophrenia Spectrum Disorders (1.5%) Substance Abuse Disorders 47% (OR = 4.6) Alcohol 33.7% Drug 27.5%

13. Antisocial Personality Disorder (2.6%) - Substance Abuse Disorders 83.6% Alcohol 74% Drug 42%

14. Borderline Personality Disorder (0.2%-1.8%) n Second only to mood disorders, ASPD n 25-67% of BPD receiving treatment have substance use disorders n 57% when not used substance abuse as a criteria Miller, 1994, Dulit, 1990, Dimeff, Principles of Addiction Medicine, 3 rd Ed, Chase, 2003Miller, 1994, Dulit, 1990, Dimeff, Principles of Addiction Medicine, 3 rd Ed, Chase, 2003

15. Alcohol Disorders (%M ental Disorders= 36.6%) OR Anxiety Disorder19%1.0 ASPD14%21.0 Affective Disorders13%1.9 Schizophrenia4%3.3

16. Drug Disorders (% mental disorders= 53%) OR Anxiety Disorders28%2.5 Affective Disorders26%4.7 ASPD18%13.4 Schizophrenia7%6.2

17. Relationship between Psychiatric Symptoms and Abstinence

18. Remission of Depressive Symptoms with Abstinence Weeks 40% 20% 30% 10% 0% 124163 Abstinence Brown S, Schuckit M. J Stud Alcohol. 1988;49:412-417. % Patients with Moderate Depression N=177, no pre-existing mood syndrome

19. Hamilton depression scores during 4 weeks of hospitalization Brown S, Schuckit M. J Stud Alcohol. 1988;49:412-417.

20. Anxiety scores during 4 weeks of hospitalization Brown S, Irwin, M. Schuckit M. J Stud Alcohol. 1991;52:55-61.

21. Diagnostic Issues n n A PERIOD OF ABSTINENCE (JAIL/ PRISON, HOSPITAL) n n SUSTAINED PSYCHIATIRC SYMPTOMS DURING ABSTINENCE (AMOUNT OF TIME REQUIRED??) n n ONSET OF PSYCHIATRIC SYMPTOMS VERSUS SUBSTANCE ABUSE PROBLEMS (PRIMARY VS. SECONDARY) n n FAMILY HISTORY OF PSYCHITRIC ILLNESSES n n CROSS SECTIONAL VERSUS LONGITUDINAL DIAGNOSIS

22. Psychotic symptoms and abstinence n 165 chronic psychotic patients with cocaine abuse or dependence n 6 weeks of abstinence needed for diagnosis of schizophrenia n 81% could not make a definitive diagnosis u 78% insufficient abstinence, 24% poor memory u After 18 months, 75% still diagnostic uncertain F Shaner, Psych Ser, 1996

23. Diagnosis of Dual Diagnosis Patients

24. Heterogeneous Population of Dual Diagnosis Patients n Addiction Only n Mildly-Moderately Severe n Highly Severe n Diagnostic Uncertainty Mee-Lee, David (2001) ASAM PPC-2R. ASAMMee-Lee, David (2001) ASAM PPC-2R. ASAM Tsuang, J, Shaner, 1997Tsuang, J, Shaner, 1997

25. Addiction Only Patients n Patients with substance abuse or dependence problems n No axis I and/or II psychiatric diagnosis or mental health issues n Need addiction service only

26. Mildly to Moderately Severe n Sub threshold diagnosis (traits of Axis I or II psychiatric disorders) n Diagnosis of Axis I or II, stable on treatment u Anxiety or mood disorders- stable u Bipolar mood disorder- resolving u Need primary substance abuse treatment, available psychiatric treatment capability

27. Highly Severe n Axis I or II psychiatric diagnosis-unstable u Schizophrenia spectrum disorders u Severe mood disorders with psychosis u Severe anxiety disorders u Severe personality disorders n Needs concurrent psychiatric and substance abuse treatment

28. Diagnosis Uncertainty n n Time n n Additional information n n Newer, effective and safe medications n n Treat unclear diagnosis?

29. Integrated Treatment Program Treatment approach - Combine mental health/Substance abuse treatment -Outpatient/inpatient - Comprehensiveness - Medication management - Outreach - Social support Drake, Psych Ser 2001, Tsuang, Psych Ser 1999, Ho, AJP 1999 Drake, Psych Ser 2001, Tsuang, Psych Ser 1999, Ho, AJP 1999

30. Pharmacological Treatment of Dual Diagnosis Patients

31. Pharmacological Treatment of Affective Disorders n Tertiary/Secondary Amines (Serotonin/NE)- Amitriptline, Desipramine n Monoamine Oxidase Inhibitors (Serotonin/ NE/Dopamine)- Phenelzine, tranlcypromine n Selective Serotonin Reuptake Inhibitors (Serotonin)- Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Citalopram (Celexa)

32. Pharmacological Treatment of Affective Disorders n NE-Dopamine Reuptake Inhibitors - Bupropion n Nontricylic Serotonin-NE Reuptake Inhibitors-Venlafaxine n Serotonin Antagonist& Reuptake Inhibitors- Nefazodone, Trazodone n NE-Serotonin Antagonist-Mirtazapine (Remeron)

33. Treatment of Depression and Alcohol Addiction n TCSs (Imipramine, desipramine) n SSRIs (fluoxetine, sertraline, nefazodone) u McGrath, 1996, Mason, 1996, Gorelick 1989, Cornelius, 1997, Pettaniti, 2000, Boy-Byrne, 2000)

34. Treatment of Depression and Opioid Addiction n TCAs (doxepin, amitriptyline, desipramine, imipramine) for methadone patients u Brady, 2003 ASAM

35. Treatment of Depression and Cocaine Addiction n TCAs (desiprmaine) n NE-Dopamine Reuptake Inhibitors - Bupropion n Nontricylic Serotonin-NE Reuptake Inhibitors-Venlafaxine u Rao, 1995, Weiss, 1989, Kosten, 1989

36. Pharmacological Treatment of Bipolar Patients n Lithium Carbonate n Valproic acid (Depakote) n Chlorpromazine n Olanzapine (Zyprexa) n Risperidone (Risperidal) n Quetiapine (Seroquel) n Lamotrigine (Lamictal) n Carbamazepine (tegretol) n Gabapentin (neurontin) n Oxcarbazepine (trileptal) n Tiagabine (gabitril) n Topirmate (topamax) Tarascon PP 2002

37. Treatments of Substance Abuse and Bipolar Disorder n Lithium n Valproate (Depakote) n Carbamazepine (Tegretol) u Brady, 2003 ASAM, Tohen, 1990, Bowden, 1995, O’Connell, 1991, Brady, 1995

38. Pharmacological Treatment of Anxiety Disorders n Benzodiazepines- Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam n Anticholingeric/Antihistaminergic- Diphenhydramine, Hydroxyzine n Barbiturates n Others-Buspirone, Chloralhydrate, Zolpidem (Ambien), Zaleplon (Sonata)

39. Treatment of substance abuse and anxiety disorders n Antidepressants (SSRIs, Trazadone, TCAs) n Anticonvulsants n Antihypertensives n Atypical antipsychotic medications n Buspirone n Bendiazepines (contraindicated) F Nitenson, ASAM 2003

40. Pharmacological Treatment of Schizophrenia n Dopamine Antagonists Haloperidol, Fluphenazine n Serotonin/Dopamine Receptor Antagonists Clozaril, Risperidone, Olanzapine, Quetiapine, ziprasidone, aripiprazole n Depo

41. Treatment of Substance Abuse and Psychotic Symptoms n Newer Atypical Agents u Reduce negative symptoms u Reduce cognitive deficits u Reduce severity of detoxification u May improve abstinence u Cravings for substances of abuse u Not a magic bullet!! F Ziedonis, ASAM 2003, Buckley, 1998, Smelson, 1997, Farren, 2000, Tsuang, 2001, Tsuang, 2004

42. Treatment Recommendations n A period of abstinence is optimal (wait after detoxification) n Duration to wait (??) n If symptoms mild, diagnosis unclear, can wait n If symptoms severe, no remission during abstinence, early treatment justified

43. Avoid These Agents for Treatment of Substance Dependence n MAOI n Opiates n Barbiturates n Stimulants n Short Acting BZDs n Tricyclics (metabolism, cardiac conduction)

44. Pharmacological Strategies for Treatment of Substance Use Disorders n Initiate and Facilitate Abstinence n Treat Withdrawal Symptoms (acute/protracted) n Relapse Prevention u Treat Associated Psychiatric Syndromes u Decrease Craving u Aversive Agents

45. Current Pharmacological Agents for Treatment of Stimulant Dependence n Dopaminergic Agents (Agonist, partial agonist, antagonist)-Bromocriptine, Levodopa, Amantadine n Serotonergic Agents-Sertraline, Fluoxetine, Desipramine n Others- Carbamazepine, Bupropion, Selogiline, Modafinil (Provigil), Disulfiram

46. Current Pharmacological Agents for Treatment of Alcohol Dependence n BZD, Anti-Seizure Medications, Anti- Hypertensive Medications for Withdrawal n Disulfiram/Calcium Carbamide n Naltrexone (ReVia) n Acamprosate (Amino Acid Derivative)- Mimics GABAa Receptor/Amino Acid derivative n Ondansetron-SHT3 antagonist

47. Current Pharmacological Agents for Treatment of Opiate Dependence n Clonidine for Withdrawal n BZDs for Withdrawal n Naltrexone for Withdrawal and Maintenance n Methadone for Maintenance n LAAM for Maintenance n Buprenorphine for Withdrawal and Maintenance