Buprenorphine

1. Buprenorphine Joseph Merrill M.D., M.P.H. University of Washington Harborview Medical Center

2. Buprenorphine: Outline • Brief historical background • Methadone maintenance treatment • Buprenorphine: characteristics and efficacy • Buprenorphine in Washington State

3. U.S. Epidemiology and Costs • 980,000 opiate-dependent persons • Over 200,000 in methadone treatment • “Problem use” increasing • Emergency visits, crime, opiate-related deaths • Costs to society $20 billion • Health care costs $1.2 billion

4. King County • 12-15,000 opiate-dependent persons • 2% HIV prevalence • >90% Hepatitis C prevalence • 1.5% annual overdose deaths

5. King County: Heroin-Related Deaths

6. Heroin CostAverage Amount Available for $100 Bach & Lantos, 1999

7. Historical Perspective • 1910’s – 1960’s • Physicians excluded from addiction treatment • High relapse rates • 1960’s – 1970’s • Increased heroin use and crime • Introduction of methadone maintenance

8. First Randomized TrialDole et al - 1969 • Imprisoned and dependent > 4 years (N=32)

9. Addiction as a Brain Disease • Prolonged drug use changes brain function • Changes are pervasive and persist after drug use stops • Brain changes demonstrated at many levels • Molecular • Cellular • Structural • Functional

10. Methadone Maintenance:Expansion and Regulation • Rapid expansion to reduce crime • 400 patients in 1968 to 73,000 in 1973 • Program quality inconsistent • Fear of methadone “diversion” • Regulation of methadone • Controlled Substances Act • FDA, DEA and state oversight • Physicians cannot prescribe for addiction

11. Methadone Maintenance:Treatment Outcomes • Methadone: • Reduces overall and overdose deaths • Drug use • Criminal behavior • Spread of infectious diseases (HIV, TB) • Not a cure

12. Frequency of Heroin Use & Methadone Dose Level Past month IV drug use (%) Adapted from V. Dole (1989) JAMA, 282, p. 1881

13. Reduction of Heroin Use By Duration of Methadone Treatment Pre- treatment Admission: < 6 months stay Average Stay: 6 to 54 months Long-term: > 54 months Adapted from: Ball & Ross, 1991.

14. Return to I.V. Drug Use Following Termination of Methadone Treatment % IV USERS Months Since Dropout Adapted from: Ball & Ross, 1991.

15. Methadone Maintenance:How Long? • Randomized trial of 179 patients • Maintenance versus 180-day psychosocially enriched detoxification • Maintenance resulted in greater treatment retention and less heroin use • No support for diverting resources from maintenance to long-term detoxification JAMA 2000;283:1303-10

16. Methadone Maintenance:Limitations • Highly structured program (6 days/week) • Limited clinical flexibility • Minimal medical services • Expansion often opposed • Treatment access limited • Stigma

17. Methadone Maintenance Policy • Policy Progress • Expansion of “medical maintenance” • Regulatory change to accreditation model • Policy Limitations • Medical maintenance applies to few patients • Initiation of methadone in physician practices not yet approved

18. Buprenorphine:New Office-Based Option? • Partial opiate agonist • Less overdose potential • Less physical dependence • Binds mu-receptor strongly • Buprenorphine pharmacokinetics • Not absorbed PO; given SL • Slow onset, long duration • Once a day or every other day dosing

19. Full Agonist vs Partial Agonist 100 90 Full Agonist 80 70 Activity 60 Partial Agonist 50 40 30 20 Antagonist 10 0 -10 -9 -8 -7 -6 -5 -4 Log Dose of Opioid

20. Buprenorphine • Comparable to methadone in most studies • With naloxone, reduced abuse potential • Advocated for physician-based practice • Good candidate for initial opiate therapy • Being studied as a detoxification agent • Now FDA approved for addiction treatment

21. Buprenorphine Efficacy • RCT of 40 Swedish patients ineligible for methadone but >1 year of dependence • Control group given buprenorphine taper (1 week) • Both groups given weekly CBT • One-year outcomes: • Treatment retention 75% vs 0% • 75% urine test negative in buprenorphine group • Addiction severity improved over time • Mortality benefit in small sample (p=0.015)

22. Drug Addiction Treatment Act: October 2000 • Amends the Controlled Substances Act • Allows Schedule III-V drugs approved for addiction to be used by MDs outside Opiate Treatment Programs • Requires MD training and registration • MD must have psychosocial referral capacity • Limits any group practice to 30 patients

23. Buprenorphine in France • Permitted for addiction treatment since 1996 • Limited oversight of generalist physicians • Estimated 67-89,000 patients by 2000 • Lessons: • Generally good treatment retention • Overdose deaths rare (associated with benzos) • Abuse/IV use of sublingual tablets documented

24. Challenges for Buprenorphine • Current and potential future Federal limitations • Training for physicians • Integration of medical and addiction services • Confidentiality of drug treatment records • How to pay for it!

25. Buprenorphine in WA State • Facilitate and evaluate the development and implementation of a pilot office-based buprenorphine program within the Washington State Medicaid program • Funded by the RWJ Substance Abuse Policy Research Program

26. Research Aims • To document the policy and protocol development of a public-sector buprenorphine program • To implement and evaluate a physician training and clinical support program • To evaluate the feasibility and outcomes of a pilot Medicaid buprenorphine program

27. Policy and Protocol Development • Key Collaborating Agencies • WA State Division of Alcohol and Substance Abuse • Medical Assistance Administration (Medicaid) • Harborview Medical Center • Evergreen Treatment Services

28. Policy and Protocol Development • Key Policy Issues • Financing of medical, pharmacy, addiction counseling services • MD recruitment, licensing, training, monitoring • Clinical Protocols • Visit requirements and take-home doses • Urine testing and responding to continued use • Diversion control and call-backs

29. Physician Training • Federal requirements • 8-hour training • ASAM training course May, 2003 • Ongoing clinical support • Evaluation • Satisfaction with training, support, clinical care • Attitudes

30. Pilot Program Evaluation • To understand the effects of a policy of public funding for buprenorphine treatment • 100 Medicaid patients (not managed care) • Randomized to immediate vs delayed office-based buprenorphine • All patients followed for one year after randomization

31. Patient Measures • Collected at baseline, 3, 6, 9 and 12 months • Addiction Severity Index • Service Use • Medical, criminal justice, travel, etc. • Other • HIV risk, treatment preferences, satisfaction • Urine toxicology

32. Buprenorphine in WA State:Summary • Key opportunity to expand access to opiate addiction treatment • Develop the financial policy and clinical protocols linking medical and addiction treatment • Provide preliminary cost and outcome data for office-based buprenorphine treatment

33. Current Issues • Psychosocial services funding • State budget crisis • King County commitment • Medicaid limitations on pharmacy benefit (Draft) • Requires participation in state drug treatment program • Limited duration of treatment • Physician recruitment • Coordination of medical and addiction services

34. Buprenorphine: Where To Get It? • Self-pay or insured: • Buprenorphine physician locator • Few physicians with limited treatment slots • Public Funding: • Only for GAX or CNP coupons (not GAU) • May be unavailable outside pilot program • Now permitted in Opioid Treatment Programs

35. Summary • Buprenorphine has potential to expand treatment access and physician involvement in addiction treatment • Substantial limitations exist, especially regulatory restrictions and cost • Methadone maintenance remains a major treatment option

36. To Learn More:buprenorphine.samhsa.gov