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

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

6. Onset of Substance Abuse in ADHD Adults (Retrospectively Derived) 0102030405060 0.0 0.2 0.4 0.6 0.8 1.0 ADHD Control Age of Onset Probability Wilens TE, et al. J Nerv Ment Dis. 1997;185(8):475-482. * *p<.05 vs control

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 index 1 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 vs. No Use, controlling for SES and Conduct Disorder (Wilens et al., APA 2004) *p=0.039 ADHD Control

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 vs. No Use, controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004) p=0.04 ADHD Controls

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) *p=0.801 *p=0.012 (Wilens et al., APA 2004)

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 *p=0.058 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)

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. (Wilens TE. Psych Clin N Am: 2004). 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

23. MGH Longitudinal Study of ADHD Medication 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 ADHD Medication Questionnaire  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? (continued)

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 Use Alcohol 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? 11% 10% 14%

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

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

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

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?