Timothy E. Wilens, MD Massachusetts General Hospital Harvard Medical School

1. Subtypes of ADHD Related to Substance Use Disorders (SUD): Results from the MGH Longitudinal Study of Boys with ADHD Timothy E. Wilens, MD Massachusetts General Hospital Harvard Medical School Funding: NIDA RO1 DA1441 & DA 11929 (TW)

2. Disclosures Dr. Wilens has served as a consultant, speaker, or has received grant support from the following • NIH (NIDA, NICMH, NIMH) • Abbott, Celltech, Glaxo/SKB, Lilly, McNeil, Neurosearch, Novartis, Pfizer, Shire • Some of the products discussed are not FDA approved for ADHD or other psychopathology; others may not be FDA approved in the manner discussed (e.g. dosing, patient groups, combination therapy)

3. ADHD Overview • ADHD is the most common neurobehavioral disorder presenting for treatment in youth • Prevalence: 6-8% youth worldwide; 4% of adults • Associated with impairment in multiple domains • Majority with comorbid learning disabilities & psychiatric comorbidity including conduct disorder • Treatment includes educational, psychotherapeutic, and psychopharmacological interventions (Goldman, JAMA:1998; Wilens et al Ann Rev Med, 2002; Faraone et al., World Psych; 2003; Kessler et al, APA 04)

4. Overlap Between ADHDand Substance Use Disorders (SUD) Substance Abuse/Dep ADHD • Excessive overlap of ADHD in SA • ADHD±comorbidity is a risk factor for SA (Wilens et al., Psych Clin N Am: 2004)

5. Smoking in ADHD Adolescents (Mean 15 years) (Conduct Disorder accounting for differences) p<0.003 vs cntrls % Smoking 11 24 (Millberger et al., JAACAP 1997)

6. 1.0 0.8 0.6 0.4 0.2 0.0 0 10 20 30 40 50 60 Onset of Substance Abuse in ADHD Adults(Retrospectively Derived) ADHD Control * *p<.05 vs control Probability Age of Onset Wilens TE, et al. J Nerv Ment Dis. 1997;185(8):475-482.

7. Lifetime Rates of SUD in Controlled Longitudinal Studies of ADHD Adults Mean age range at follow-up: 18-26 years Total ADHD N=845, total Control N=1085 % with SUD ( from Wilens et al., Psych Clin N Am: 2004)

8. SUD in Young Adults with ADHD Methods • Male subjects ascertained from an ongoing longitudinal family study of ADHD. • Case matched controls (at baseline) • Data obtained from year 10 • Diagnosis(es) by KSADS/SCID • Raters blinded to ascertainment (Wilens et al., APA 2004)

9. SUD in Young Adults with ADHD SUD Monitoring • Subjective measures • Drug use severity index1 • Self-report measure • Items including frequency and severity (problem) • Items relative to initiation and continuation • Module from DSM on SA • Semi-structured interview • Direct report of proband to interviewer • Indirect report of parent to interviewer • Best estimate diagnosis • Objective measures • Urine by radioimmunoassay (RIA)-hospital analysis including osmolality 1. Tarter RE, Hegedus AM. Alcohol Health Res World. 1991;15:65-73.

10. Nicotine Use in Male Probands at 10 year Follow-up (Age 21 yrs), Any Use *p=0.039 Control ADHD (Wilens et al., APA 2004) *p=0.039 vs. No Use, controlling for SES and Conduct Disorder

11. Nicotine Use in Male Probands at 10 year Follow-up (Age 21 yrs), Stratified by Frequency of Use OR=3.2 *p=0.04 (Wilens et al., APA 2004)

12. Nicotine Use in Male Probands at 10 year Follow-up (Age 21yrs), Stratified by Comorbidity with Conduct Disorder (CD) *p=0.359 *p=0.141 (Wilens et al., APA 2004)

13. Marijuana Use in Male Probands at 10 year Follow-up, Any Use p=0.04 Controls ADHD (Wilens et al., APA 2004) *p=0.04 vs. No Use, controlling for age, SES and Conduct Disorder

14. Marijuana Use in Male Probands at 10 year Follow-up, Stratified by Frequency of Use OR=2.7 *p=0.114 (Wilens et al., APA 2004)

15. Marijuana Use in Male Probands at 10 year Follow-up, Stratified by Comorbidity with Conduct Disorder (CD) (Wilens et al., APA 2004) *p=0.012 *p=0.801

16. Reason for First Use of Preferred Drug:To Get High OR=2.0 *p=0.1 *p=0.1 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)

17. Reason for First Use of Preferred Drug:To Change Mood OR=2.8 *p=0.058 (Wilens et al., APA 2004) *p=0.058 controlling for age, SES and Conduct Disorder

18. Reason for First Use of Preferred Drug:To Sleep Better OR=5.4 *p=0.061 *p=0.061 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)

19. Continued Use of Preferred Drug:To Get High OR=1.7 *p=0.316 *p=0.316 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)

20. Continued Use of Preferred Drug:To Change Mood OR=2.4 *p=0.121 *p=0.121 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)

21. Continued Use of Preferred Drug:To Sleep Better OR=5.7 *p=0.03 *p=0.03 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)

22. Apparent ages of risk for SUD related to ADHD and ADHD comorbidity (BPD, CD, BPD+CD) • Age of SA onset • Comorbid ADHD: 12-16 years • Noncomorbid ADHD: 17-22 years • Females earlier onset than males • ADHD impact starts approximating comorbidity • “Start talking about it in 10-12 year olds” • Cigarette use • 50% of stable cigarette users with ADHD manifest SUD (Wilens TE. Psych Clin N Am: 2004).

23. MGH Longitudinal Study of ADHDMedication Questionnaire • Query of medication use • Pilot data • Seven questions regarding appropriate use of prescribed medications • Self-report on those who were taking meds • Not psychometrically validated • Longitudinal study of ADHD (and controls) • 10 year follow-up data (mean age 19 years) • Data available on 55 ADHD and 43 controls • Psychopathology by KSADS (baseline)

24. MGH Longitudinal Study of ADHDMedication Questionnaire (continued) • Have you sold the medication prescribed by your doctor? • Have you used more of your medication than you were supposed to? • Have you gotten high on your medication? • Have you misused your medication?

25. MGH Longitudinal Study of ADHD Medication Questionnaire(continued) • Have you not taken your medication so that you could use drugs or alcohol? • Have you used alcohol or drugs on the days you take your medication? • Have you had a reaction to drugs or alcohol while taking your medication?

26. Sold Prescribed Medication p=0.025 11% 0%

27. Misused Medication p=0.006 22% 2%

28. Used More Medication p=0.018 22% 5%

29. Gotten High From Medication p=0.414 9% 5%

30. Skipped Medication to UseAlcohol or Drugs p=0.027 16% 2%

31. Used Medication with Alcohol or Drugs p=0.6 31% 26%

32. Reaction to Alcohol or Drugs with Medication p=0.125 5% 0%

33. Diverting medication… Who is at risk? 14% 11% 10%

34. Diversion of Medications and ADHD Comorbidity 100% 83% 83%

35. Misuse of Medication… Who is at risk? 22% 21% 14%

36. Misuse of Medication and ADHD Comorbidity 83% 75% 59%

37. Diversion and Misuse of Medications in ADHD • All cases receiving immediate-release stimulants • Methylphenidate • Amphetamine • No evidence of diversion or misuse of • Extended-release stimulants (e.g. OROS MPH) • Nonstimulants (TCA, bupropion, clonidine)

38. Limitations • Relatively small sample size • Especially for med questionnaire • Data generalize to males only • Data from “middle class” sample • Data presented today based on self report • Medication questionnaire not psychometrically validated • Other comorbidities and mediators of SUD not examined for these analyses

39. Summary: ADHD+Substance Abuse • ADHD is a risk factor for Cigarette Smoking • ADHD is a risk factor for any and heavy substance use • Adolescent-onset clearly linked to conduct disorder (and Bipolar disorder) • Later onset probably more linked to ADHD • Evidence of self medication • Attenuation of mood • Soporiphic effects of medication • Evidence of diversion and misuse of immediate release stimulant medication in ADHD • High risk groups (those with ADHD+SUD+Conduct) • Need to discuss proper storage and use of medications

40. QUESTIONS?