1. Kathleen M Carroll PhD Yale University School of Medicine Dual Addictions Kathleen M Carroll PhD Yale University School of Medicine

3. Overview Definitions and terms Epidemiology: Rates and risks Onset: Gateways and destinations Treatments: Everything we don’t know

5. Terms Comorbidity: Co-occurrence of two conditions or disorders Dual diagnosis: Co-occurrence of alcohol/drug use disorder and another psychiatric disorder (heterotypic comorbidity) Homotypic comorbidity: Co-occurrence of disorders within a diagnostic grouping (e.g., substance use disorders)

6. Major US epidemiologic surveys Epidemiologic Catchment Area Study (ECA) 1980- 1984 N=20291 adults 18+ DSM-III (DIS) Regier et al., 1990 National Comorbidity Survey (NCS) 1990- 1992 N=8098 15-54 DSM-III- R (CIDI) Kessler et al. 1994 NCS-R 2001- 2002 N=9282 adults DSM-IV (CIDI) Kessler et al. 2005 **NESARC 2001- 2002 N=43093 adults DSM-IVGrant et al., 2004

7. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Previous surveys in US, Canada, Australia confirm probabilities of alcohol use disorder rise with drug use disorder visa versa Only NESARC diagnosis specific (multiple types of drugs rather than ‘lumping’) Includes data on help seeking Focus on 12-month (current), rather than lifetime disorders Oversampling of African Americans and Hispanics

8. DSM-IV Substance Dependence M aladaptive use leading to clinically significant impairment or distress, shown by 3+ of the following in the same 12-month period: 1. Use of the substance more or longer than intended 2. Persistent desire or unsuccessful efforts to cut down or stop 3. A great deal of time spent on use of the substance or getting over its effects 4. Important activities given up or reduced because of use 5. Continued use despite knowledge of a serious physical or psychological problem 6. Tolerance 7. Withdrawal, or use to avoid withdrawal

10. DSM-IV Substance Abuse N ot dependent, and maladaptive use leading to clinically significant impairment or distress, shown by 1 + of the following: 1. Continued use despite social/interpersonal problems 2. Hazardous use (e.g., driving when impaired by alcohol) 3. Frequent use leading to failure to function in major roles 4. Legal problems

12. NESARC: 12-month prevalence rates Disorder 12-month prevalence Population estimate (thous) Any alcohol use disorder 8.517580 Any alcohol use only 7.415285 Any drug use disorder 2.04159 Any alcohol use + drug use disorder 1.12295 Any drug use disorder only 0.91864 Any drug abuse 1.42858 Any drug dependence 0.61301 Stinson et al, (2005) DAD

13. 12-month prevalence: Drug use disorders Disorder % abuse% dependencePop est (thou) Cannabis1.130.323016 Opioid.24.11737 Cocaine.13 557 Amphetamine.09.07342 Sedative.09.07333 Hallucinogen.12.02291 Tranquilizer.08.05260 Solvent/ inhalant.02-49 Stinson et al, (2005) DAD

14. Demographics: Users of alcohol + drugs more likely to be: Male (74%) Younger (18-29) (65%) Never married (63%) Similar to drug-only with respect to education, ethnicity, income

16. DisorderPrevalence (%) Any drug dependence67.7 Any drug abuse49.5 Cocaine79.5 Hallucinogen79.2 Amphetamine62.8 Solvent /inhalant abuse59.9 Opioids57.5 Cannabis57.6 Tranquilizers57.5 Sedatives39.8 Rates of alcohol use disorders among those with specific drug use disorders: NESARC

17. % alcohol use disorder, given drug use % drug use disorder, given alcohol use Any drug dependence67.75.01 Any drug use49.58.04 Cocaine79.52.51 Hallucinogen79.21.31 Amphetamine62.81.22 Solvent /inhalant59.90.17 Opioids57.52.41 Cannabis57.69.89 Tranquilizers57.50.85 Sedatives39.80.75 Alcohol use among those with specific drug use disorders and visa-versa

18. Comorbidity: NESARC DisorderNo alcohol or drug Alcohol only Drug only Alcohol + any drug Any personality disorder 13.225.344.050.8 Any mood disorder, past yr 8.116.427.535.3 Any anxiety disorder, past yr 10.415.624.026.5 Stinson et al, (2005) DAD

19. 12-month prevalence treatment seeking by disorder: NESARC Stinson et al, (2005) DAD

20. 12-month prevalence treatment seeking by disorder: NESARC

21. Factors associated with multiple substance use Retention of use through gateway progression Pharmacologic effects of combinations, including modulation, treatment of withdrawal and uncomfortable effects Genetic evidence of common mechanisms, vulnerability in some families Availability, market trends

22. Gateway pattern of drug initiation: Kandel et al Cigarettes Alcohol Cannabis Other illicit NCS-R: Only 5.2% Violate this pattern

23. Risk of developing disorder, given use Anthony et al. 1994, Comparative epidemiology, NCS

24. NESARC: Hazard rates for alcohol and drug use disorders Hasin et al., 2007 Arch Gen Psychiatry Compton et al. 2007 Arch Gen Psychiatry

26. Drug-alcohol comorbidity associated with: Earlier onset Higher severity Higher psychiatric comorbidity Higher rates of treatment seeking Higher rates of dropout once in treatment Less socioeconomic support Poorer treatment outcome

28. Limited research on treatment of homotypic comorbidity Users of multiple substances usually excluded from treatment research: Difficulty in meeting needs of heterogeneous populations in single trial Complexity of assessment (time frame, availability of biologic indicators, time) Complexity of targeting multiple substances simultaneously (licit, illicit) Safety and compliance concerns, especially in pharmacologic trials Pharmacologic specificity Rounsaville et al, 2003

30. Available pharmacotherapies for substance use disorders AlcoholOpioidsCocaineMarijuana DetoxificationXx-- MaintenanceX AntagonistX Aversive, reduce craving X Treat co-existing psychiatric disorders XXXX

31. Emerging pharmacologic strategies for homotypic comorbidity TypeMedicationReference Opioid  alcohol NaltrexoneVolpicelli et al (1992) O’Malley et al (1992) Alcohol  cocaine DisulfiramCarroll et al. (2004)

33. Original rationale for disulfiram as treatment for cocaine users Clinical observation of high levels of concurrent alcohol-cocaine use (60-70% of patients) Rationale: Reducing alcohol use may reduce concurrent cocaine use 1. Better ability to utilize coping skills (Marlatt et al) 2. Alcohol powerful conditioned cue (Higgins et al) 3. Cocaethylene (Jatlow, McCance)

34. Open outpatient study, cocaine- alcohol users: % attaining 3+ weeks abstinence Carroll et al., 1998

35. Double blind trial of disulfiram for cocaine dependence in methadone maintenance N=67 Petrakis et al 2000

36. Randomized outpatient clinical trial: Disulfiram, CBT, and IPT, N=121 Carroll et al., 2004

37. zp Time-7.15.00 Disulfiram x time-2.10.04 CBT x time-2.33.03 Disulfiram x CBT x time -1.97.05 Cocaine outcomes for those who did NOT meet criteria for alcohol abuse or dependence (n=58)

38. Behavioral therapy studies of alcohol-drug users

39. Behavioral therapies tend to be effective across types of substance use Alcohol OpioidsCocaineMarijuanaMixed Motivational interviewing X(X) X Contingency management XXXXX* Cognitive behavioral therapies XXXXX Behavioral couples, family therapies XXXXX

40. Clinical Trials Network: 17 Current Nodes, >200 CTPs

41. Clinical Trials Network: MET Trials Participant Characteristics Mean age 35 29% female (<MI) 42% Caucasian (<MI) 12 years of education 28% mandated or legal referral Primary substance use problem: Alcohol: 29 % (<MI) Marijuana: 16% Cocaine: 23% (>MI) Methamphetamine: 4% (<MI) Opioids: 9% Benzodiazepenes: 1% Ball et al., 2007

42. CTN MET/MI studies: Design

43. CTN: MET longitudinal outcomes Ball et al.., 2007

44. CTN MET/MI studies: Outcomes for alcohol subgroups EngagementSubstance use outcomes Alcohol use only subgroup MI (1 session) Carroll et al. (2007) +- + MET (3 sessions) Ball et al. (2007) -(+) + MET- Spanish (3 sessions) Under review -- +

45. ‘CBT 4 CBT’ Computer Based Therapy/CBT 6 modules, ~1 hour each, high flexibility Highly user friendly, no text to read, linear navigation Video examples of characters struggling real life situations Multimedia presentation of skills Repeat movie with character using skills to change ‘ending’ Interactive exercises, quizzes Multiple examples of ‘homework’

46. Computer-based training in CBT: CBT4CBT “All comers”: few restriction on participation, only require some drug use in past 30 days 43% female 45% African American, 12% Hispanic 23% employed 37% on probation/parole 59% primary cocaine problem, 18% alcohol, 16% opioids, 7% marijuana 79% users of more than one drug or alcohol Carroll et al., in press, Am J Psychiatry

47. Primary outcomes, 8 weeks CBT+TAU versus TAU Carroll et al., in press, Am J Psychiatry

49. Treatment of Dual Addictions: General strategies Target, treat most severe disorder and any requiring detoxification first Utilize pharmacotherapies when available Attend to psychiatric and medical comorbidity Frequent monitoring, chronic care model Sequential targeting may be important for some treatments (eg. contingency management)

50. “I wonder why we’re not getting any new converts.”