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

13. Adapted from: Ball & Ross, 1991. 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

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

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

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