1. VERSION VIII (i), August 14, 2003 BUPRENORPHINE/NALOXONE- FACILITATED REHABILITATION FOR OPIOID DEPENDENT ADOLESCENTS/YOUNG ADULTS PI: George E. Woody, M.D. Co-PI: Robert F. Forman, Ph.D. Project Director: Sabrina Poole

2. Node Expert & Co-Investigator: Laura McNicholas, M.D., Ph.D. NIDA Proj. Collaborator: Jack Blaine M.D. NIDA Med. Specialist: Ming Shih Ph.D. Data Management: Chris Petro, B.A. Biostatistician: Kevin Lynch, Ph.D. Consultants: Howard Moss, Ph.D. & Paul Fudala, Ph.D.

3. Background Increase in opioid dependence: heroin and prescription opioid use Increase in opioid dependence: heroin and prescription opioid use Many health care providers reluctant to use methadone maintenance for persons with short history of dependence Many health care providers reluctant to use methadone maintenance for persons with short history of dependence Treatment typically = detoxification & psychosocial rehabilitation Treatment typically = detoxification & psychosocial rehabilitation

4. Background (cont) Clinicians report relapse common Clinicians report relapse common Very little data on patients in 14-21 year old age group on response to agonist treatment and relapse potential Very little data on patients in 14-21 year old age group on response to agonist treatment and relapse potential Some clinicians say relapse just as common as in older persons with opioid dependence Some clinicians say relapse just as common as in older persons with opioid dependence Others say that shorter dependence history more likely to result in lower relapse Others say that shorter dependence history more likely to result in lower relapse

5. Figure 1 - DAWN Mentions of Heroin by Age Group 1995-99

6. Potential of Buprenorphine High margin of safety High margin of safety Can be used in office-based practice Can be used in office-based practice Less chance of interacting with older, hard- core addicts that occurs with methadone Less chance of interacting with older, hard- core addicts that occurs with methadone More flexible with take-homes More flexible with take-homes Less physiological dependence Less physiological dependence

7. Total N = 240 Screening Assent/Consent Screening If EligibleIf not eligibleEnd of process Study Assent/Consent Quiz and Process Urn Randomization: Gender; Race (Non-Cauc/Cauc); Rt. Admin; Age (14-17; 18-21) TAU (Detox + 2 x/wk Psychosocial Rx X 12 wks) N= 120 TAU (Detox + 2 x/wk Psychosocial Rx X 12 wks) N= 120 Evaluations: weekly X 12 wks (+/- 2 day window of opportunity); Comprehensive @ 4, 8, 12 wks (+/- 1 wk window of opportunity), 24, 36, and 52 wks (+/- 3 wk window of opportunity Study Schema

8. Entrance Criteria  Medical or psychiatric disorders that would make participation hazardous  DSM-IV-TR Opioid Dependence with physiologic features  Informed consent  Parental consent if <18  Adequate transportation  No immediate plans to leave area or enter jail, hospital or methadone program

9. Sites Brandywine Counseling, Newark, DE - a methadone program; J. Glick, M.D. Brandywine Counseling, Newark, DE - a methadone program; J. Glick, M.D. Mountain Manor, Baltimore, MD - a full service youth rehabilitation program; G. Subramanian, M.D. Mountain Manor, Baltimore, MD - a full service youth rehabilitation program; G. Subramanian, M.D. Duke Addictions Program, Durham, N.C. - adolescent treatment; L. Handlesman, M.D. Duke Addictions Program, Durham, N.C. - adolescent treatment; L. Handlesman, M.D. Univ. of N. Mexico, Albuquerque; Ayundantes, Espanola, N.M. - methadone programs; M. Bogenschutz, M.D. Univ. of N. Mexico, Albuquerque; Ayundantes, Espanola, N.M. - methadone programs; M. Bogenschutz, M.D.

10. Baseline Data as of 4/16/04 54 screened 54 screened 31 randomized 31 randomized Screening failures: Screening failures: –8 urine test failure (4 + benzo; 3 + meth.; 1- op –6 met criteria but no show for randomization –3 ECG abnormal –2 liver enzyme > 5X top limit of normal –2 transportation problems

11. Baseline (cont) MalesFemales MalesFemales Gender 22 9 Gender 22 9 Mean Age 18.6 20.3 Mean Age 18.6 20.3 Caucasian 18 6 Caucasian 18 6 Non-Cauc. 4 3 Non-Cauc. 4 3

12. Baseline (cont) Drug UseYearsPast 30 Days Drug UseYearsPast 30 Days Heroin Heroin Other Opiates Other Opiates Cocaine Cocaine Amphetamines Amphetamines