1. Copyright Alcohol Medical Scholars Program 1 Opioid Agonist Treatment: “Trading one substance for another?” Joseph Sakai, M.D.

2. Copyright Alcohol Medical Scholars Program 2 Objectives: Opioids and opioid dependence Natural course Methadone Other agonist treatments

3. Copyright Alcohol Medical Scholars Program 3 Opioids, Opioid Dependence: Define opioids –Opiates –Semi-synthetic –Synthetic

4. Copyright Alcohol Medical Scholars Program 4 Opioids, Opioid Dependence: Endogenous opioid system –Receptors Mu Delta Kappa –Endorphins Beta-endorphins Enkephalins Dynorphins

5. Copyright Alcohol Medical Scholars Program 5 Opioids, Opioid Dependence: Opioid dependence: Tolerance Withdrawal Use more than intended Unable to cut down Increased time using Give up other activities Use despite consequences

6. Copyright Alcohol Medical Scholars Program 6 Opioids, Opioid Dependence: Epidemiology –Lifetime use 1.8% of 10 th graders used heroin (lifetime) 3.6 million Americans have used heroin –Dependence 1:4 heroin users with lifetime dependence 1:1000 in US with opioid dependence in 2002

7. Copyright Alcohol Medical Scholars Program 7 Natural Course: Detox alone high relapse 20 yr after detox –10% stable abstinence at 5yrs –35% stable abstinence at 18 year 24 yr f/u –~20% no heroin use: last 10 yrs of the study

8. Copyright Alcohol Medical Scholars Program 8 Natural Course: Medical risks: –Abscesses –Sepsis –Osteomyelitis –Thrombophlebitis –Endocarditis

9. Copyright Alcohol Medical Scholars Program 9 Natural Course: Medical risks: –HCV 70% IV users 65% after 1 yr needle use; ~85% at 5 yrs –HIV IV users ~75% of new HIV infections HIV ~20%

10. Copyright Alcohol Medical Scholars Program 10 Natural Course: Death –Overdose 1.5%/yr –24 yr study – 28% sample deceased –Not in tx; 63x expected mortality rate Low employment: –36.4% active users employed –Heroin dosed Q 6 hours –Need time to recover –But need money to buy the drug

11. Copyright Alcohol Medical Scholars Program 11 Natural Course: Crime: –Most commit crimes –F/u 10 years ~18% incarcerated –One study n=573 12 month period: >80,000 crimes reported Costs: –Medical costs: $1.2 billion per yr –Total cost estimate: $20 billion per yr

12. Copyright Alcohol Medical Scholars Program 12 Natural Course: Summary Unlikely to remit with detox alone Medical risks High mortality Low employment Crime High cost to society

13. Copyright Alcohol Medical Scholars Program 13 Treatment: Goals Complete abstinence Reduce use of heroin Reduce harm Increase employment Reduce crime Engage in treatment Be cost effective

14. Copyright Alcohol Medical Scholars Program 14 Treatment: Modalities Rehabilitation –Engage patient –Support abstinence –Prevent relapse –Life management skills –Coping skills

15. Copyright Alcohol Medical Scholars Program 15 Treatment: Rehabilitation –Individual –Groups –Urines –Psychosocial treatments –Medications

16. Copyright Alcohol Medical Scholars Program 16 Treatment: Antagonists –Naltrexone Pure antagonist Absorbed orally 50-150 mg/dose Dosed daily or 3x/wk Retention poor

17. Copyright Alcohol Medical Scholars Program 17 Treatment: Agonists –Theory Pre-existing dysphoria Pre-existing receptor dysfunction Induced receptor dysfunction

18. Copyright Alcohol Medical Scholars Program 18 Treatment: Methadone Mu agonist Half life 22-48 hours Dosing (slowly ↑ to 80mg +) Needs specialized clinics

19. Copyright Alcohol Medical Scholars Program 19 Treatment: Methadone ↓ Heroin use by 50% ↓ HIV 4 fold ↑ Employment 24% ↓ 50% criminal activity

20. Copyright Alcohol Medical Scholars Program 20 Treatment: Methadone ↑ Retention in rehabilitation 28 times ↑ Retention in HCV treatment ↑ Health outcomes (HCV, HIV)

21. Copyright Alcohol Medical Scholars Program 21 Treatment: Methadone ↓ Mortality 50% –Before and after methadone –In vs out of treatment Cost effective –<$13/day –4:1 cost benefit ratio

22. Copyright Alcohol Medical Scholars Program 22 Methadone: Summary Complete abstinence Reduce use of heroin Reduce harm Increase employment Reduce crime Engage in treatment Save lives Be cost effective Yes No X X X X X X X X

23. Copyright Alcohol Medical Scholars Program 23 Treatment: Barriers Out of medical mainstream Stigma of specialized clinics Location of clinics Daily dosing Federal regulations

24. Copyright Alcohol Medical Scholars Program 24 Treatment: Methadone Barriers to use of methadone Misconceptions –Methadone dependence –Trading one substance for another? –Methadone must be taken for life

25. Copyright Alcohol Medical Scholars Program 25 Treatment: LAAM (levo-alpha acetyl methadol) LAAM –Mu agonist –Orally dosed –Effects: 72 hours –Dose (20-100mg three times per week) –Licensed clinics

26. Copyright Alcohol Medical Scholars Program 26 Treatment: LAAM Retention ↓(39% vs. 60% LAAM vs. methadone) Same reduction in heroin use (55% vs. 46% LAAM vs. methadone) Safety concerns –Cardiac abnormalities (QT prolongation) –LAAM (ORLAAM) sale and distribution discontinued

27. Copyright Alcohol Medical Scholars Program 27 Treatment: Buprenorphine Buprenorphine –Agonist/antagonist –Half life 37 hrs –Dosing 8-32mg/d –Can precipitate withdrawal –Absorption (poor oral)

28. Copyright Alcohol Medical Scholars Program 28 Treatment: Buprenorphine Office based –Increased access 20% of heroin dependent persons can get methadone Methadone not available in some states –Any physician can be trained Safer in overdose Risk for diversion –Can combine with Naloxone to ↓injection

29. Copyright Alcohol Medical Scholars Program 29 Treatment: Buprenorphine Outcome –Retention in treatment Slightly lower than methadone 50% vs. 59%(buprenorphine vs. methadone) –Heroin use Slightly worse than methadone (low dose) 38% vs. 40.5% (buprenorphine vs. methadone)

30. Copyright Alcohol Medical Scholars Program 30 Conclusions: Opioid dependence is destructive Methadone maintenance is effective Other agonist treatments are available A challenge to you…