1. Opioid Pharmacotherapy: An Introduction Walter Ling, MD Integrated Substance Abuse Programs (ISAP) UCLA International Symposium on Drug Abuse and Addictive Behavior Chongqing; P.R. China September 10, 2009 lwalter@ucla.edu www.uclaisap.org

2. Scope of the Talk Effective medications Implementation: knowledge, skills and philosophy; what have we learn, so far

3. Medications for Opioid Addiction Methadone: agonist Morphine Tincture of opium Naltrexone:antagonist Depo-naltrexone Buprenorphine: partial agonist –Subutex, Suboxone, Probuphine Clonidine: non-opioid Lofexidine

4. Methadone Long acting Orally active opiate agonist capable of reducing or eliminating withdrawal signs and symptoms Reducing drug craving Normalizing physiological function

5. Methadone Treatment Reduce illicit heroin use Reduce death related to heroin addiction Reduce HIV and other infectious diseases Improve health and well being Improve gainful employment and other pro-social activities Reduce crime HIV infection rates in and out of methadone treatment (Metzger et al. 1993)

6. Cochrane Review Methadone maintenance therapy vs no opioid replacement therapy for opioid dependence Richard Mattick, Courtney Breen, Jo Kimber, Marina Davoli, Rosie Breen –Methadone maintenance is better at retaining patients in treatment and reducing heroin use, but not statistically superior in reducing criminal activities Comment: Proximal vs distal treatment outcomes

7. Adequate Dose and Duration

8. Naltrexone: The Perfect Drug Orally Effective Rapid onset of action Long duration of action Safe Few side effects Completely blocks effects of heroin Non-addicting No tolerance No dependence No withdrawal

9. Naltrexone: “Victimless Cure” One reason not to take naltrexone: Can’t get high! “It’s like taking nothing” Limited Success: Coercion or Bribery

10. Cochrane Review Oral naltrexone treatment for opioid dependence Silvia Minozzi, Laura amato, Simona Vecchi, Marina Davoli, Ursula Kirchmayer, Annette Verster; Rome, Italy –Only 2/10 studies with adequate blinding; naltrexone better than placebo in limiting heroin use during treatment, but did not reach statistical significance; less incarceration vs psychosocial treatment alone. No statistical significant benefit in treatment retention, side effects or relapse at follow up Comment by reviewers: Studies did not provide adequate data for evaluation of naltrexone treatment for opioid dependence.

11. Buprenorphine: Pharmacological Characteristics Partial Agonist (ceiling effect) high safety profile low dependence Tight Receptor Binding long duration of action slow onset mild abstinence

12. Opiate Agonist Measures Bup MS4.1 8:1 2:1 Plac Adding Naloxone to Buprenorphine Value of a Dose in Dollars Dollars Minutes Naloxone not absorbed sufficiently to interfere with buprenorphine when the combination is taken sublingually Sublingual absorption of buprenorphine @ 70%; naloxone @ 10% If injected, BUP/NX will precipitate withdrawal in a moderately to severely dependent addict

13. Buprenorphine :Cochrane Review Buprenorphine maintenance vs placebo or methadone maintenance for opioid dependence Richard Mattick, Jo Kimber, Courtney Breen, Marina Davoli; National Drug and Alcohol Research Center, Sydney, Australia Buprenorphine is an effective maintenance treatment for heroin dependence, but less effective than methadone delivered at adequate dosages Note: Data from early trials; slow induction, high withdrawal symptoms and low retention, (next slide) Treatment of HIV/AIDS: drug/drug interactions Flexibility in delivery Role in treatment of pain

14. Reduced heroin use Reduced criminal activities Increased gainful employment Improved general health –Dole VP & Nyswander ME (1965) A Medical Treatment for Diacetylmorphine (Heroin) Addiction JAMA 193: 646-650 Opiate Addiction Treatment: In the Beginning

15. Treatment of Opiate Addiction: Goals and Strategies Treatment goals: whose? –Clinician: reduce mortality and morbidity, improve health –Patient: feel better or feel good; free from hassles –Family: relief from stress, loss and shame –Society: from resource eaters to contributors Treatment goals determine treatment strategies and defining treatment success or failure

16. Pharmacotherapy of Opiate Addiction: What Can We Expect? Proximal goals: (pharmacological effects) –Alleviation of withdrawal symptoms –Reduced craving and drug use –Improved health Intermediate goals: (intervening events) –Improved employment –Taking personal responsibilities Distal goals: (changed life) –Assuming societal responsibilities –Contributing to society

17. France – Role of Political Interventions 1994: Acceptance of Harm Reduction Policy –Rapid Approval of Buprenorphine & Methadone –1996 BMT for GP use; MMT reserved for clinics –2008: 90-100,000 BMT and 10-15,000 MMT Patients Overdose deaths ↓80%; Associated crime ↓ 80%; HIV among IDU’s ↓ 40% to 11%; ~ 3500 lives saved since 2004. Carrieri, Lancet 2008 Lavignasse et al, 2002 Heroin death: five fold reduction Premature birth: 3-fold reduction

18. Summary: Successful Pharmacotherapy Clinical efficacy and safety Patient and provider acceptance Public health significance Powerful advocacy and strong leadership Regulatory and political support Favorable societal attitude –The role of the clinicians; we must change before our patients’ lives can change.

19. Thank you thank you thank you