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Medication Assisted Therapy for Opioid Addiction: Methadone and Buprenorphine

Medication Assisted Therapy for Opioid Addiction: Methadone and Buprenorphine. Andrew J. Saxon, M.D. Veterans Affairs Puget Sound Health Care System and University of Washington Seattle, WA . Disclosures. Supported by: National Institute on Drug Abuse Clinical Trials Network

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Medication Assisted Therapy for Opioid Addiction: Methadone and Buprenorphine

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  1. Medication Assisted Therapy for Opioid Addiction:Methadone and Buprenorphine Andrew J. Saxon, M.D.Veterans Affairs Puget Sound Health Care Systemand University of WashingtonSeattle, WA

  2. Disclosures Supported by: National Institute on Drug AbuseClinical Trials Network Scientific Advisory Board, Alkermes, Inc. Speaker, ReckittBenckiser, Inc.

  3. Medication Assisted Treatment • Methadone and Buprenorphine • Pharmacology • Efficacy • Starting Treatment with Agonist Replacement Therapies (START) Study • Comparing methadone and buprenorphine on • Treatment retention • Illicit opioid use • HIV risk reduction

  4. Methadone Pharmacokineticsand Dosing • Rapidly absorbed • Peak Levels in 4 hours • t1/2=24 hours • Metabolized in liver (p450 3A/4) • Doses should be individualized but higher doses generally more effective

  5. Kyle et al., 1999

  6. Swedish Methadone StudyBefore Experimental Group(Methadone) Control Group(No Methadone) Gunne & Gronbladh, 1981

  7. Swedish Methadone StudyAfter 2 Years Experimental Group(Methadone) Control Group(No Methadone) a b c d d d a Sepsisb Sepsis and Endocarditisc Leg Amputationd In Prison Gunne & Gronbladh, 1981

  8. Methadone Side Effects • Minimal sedation once tolerance achieved • Constipation • Increased Appetite/Weight Gain • Lowered Libido; May decrease gonadal hormone levels • Exhaustively studied in all other organ systems with no evidence of chronic harm

  9. Properties of Buprenorphine,a µ-Opioid Partial Agonist Ceiling effect on respiratory depression High affinity for µ-opioid receptor Slowly dissociates from µ-opioid receptors Ameliorates withdrawal once underway Can precipitate withdrawal if given in temporal proximity to full agonist opioids

  10. Efficacy: Full Agonist (Methadone) Partial Agonist (Buprenorphine), Antagonist (Naloxone) 100 90 80 70 60 50 40 30 20 10 0 Full Agonist (Methadone) % Efficacy Partial Agonist (Buprenorphine) Antagonist (Naloxone) -10 -9 -8 -7 -6 -5 -4 Log Dose of Opioid

  11. Buprenorphine Pharmacology Poor oral bioavailability; given sublingually (subcutaneous implants: experimental; patch: for pain) Slow onset (Peak effects 3-6 hrs.) Long duration (24 - 48 hours) Slow offset Half life > 24 hours

  12. Zubieta et al., 2000

  13. No. Assessed for Eligibility: 84 All Patients: Group CBT Relapse Prevention Weekly Individual Counseling Three times Weekly Urine Screens No. Excluded: 44 Not Meeting Inclusion Criteria: 41 Refused to Participate: 2 Other Reasons: 1 No. Randomized: 40 Allocated to Buprenorphine: 20 Received Buprenorphine: 20 Allocated to Detox/placebo: 20 Received Detox/Placebo: 20 Included in Analysis*: 20 Excluded from Analysis: 0 Included in Analysis: 20 Excluded from Analysis: 0 Buprenorphine Maintenance vs. Detoxification Kakko J et al. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomized, placebo-controlled trial. Lancet 361(9358):662-8, 2003.

  14. Maintenance vs. Detoxification: Retention 20 15 Remaining in treatment (nr) 10 Detox/placebo 5 Buprenorphine 0 0 50 100 150 200 250 300 350 Treatment duration (days)

  15. Detox/Placebo Buprenorphine Cox regression Dead 4/20 (20%) 0/20 (0%) c2=5.9; p=0.015 Maintenance vs. Detoxification: Mortality Kakko J et al. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomized, placebo-controlled trial. Lancet 361(9358):662-8, 2003.

  16. Buprenorphine Implants for Opioid Addiction Ling et al., 2010

  17. START Study Schema

  18. Treatment Retention

  19. Treatment Retention by Dose

  20. Opiate Positives by Dose

  21. HIV Injection Risk Behavior Risk Behavior Survey completed at baseline, week 12, week 24 Needle Sharing in Past 30 Daysamong Week 24 Completers:

  22. HIV Sexual Risk Behavior Risk Behavior Survey completed at baseline, week 12, week 24 Multiple Sexual Partners in Past 30 Daysamong Week 24 Completers:

  23. MAT for Opioid AddictionMethadone and BuprenorphineConclusions Relapse rates are high without MAT Methadone and Buprenorphine both efficacious and reduce mortality Methadone and Buprenorphine both reduce HIV risk behaviors

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