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 [email protected] www.uclaisap.org
Jan 01, 2016
Opioid Pharmacotherapy:An Introduction
Walter Ling, MDIntegrated Substance Abuse Programs (ISAP)
UCLAInternational Symposium on Drug Abuse
and Addictive Behavior Chongqing; P.R. China
September 10, [email protected]
www.uclaisap.org
Scope of the Talk
• Effective medications
• Implementation: knowledge, skills and philosophy; what have we learn, so far
Medications for Opioid Addiction
• Methadone: agonist• Morphine
• Tincture of opium
• Naltrexone:antagonist• Depo-naltrexone
• Buprenorphine: partial agonist– Subutex, Suboxone, Probuphine
• Clonidine: non-opioid
• Lofexidine
OOH O
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OHCH3 CH2
CH2 CH N
CH3CH3
CH3
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Methadone
• Long acting• Orally active opiate agonist capable of reducing
or eliminating withdrawal signs and symptoms • Reducing drug craving• Normalizing physiological function
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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
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13 15 16 17 17 18 18 19 19 20 21
HIV infection rates in and out of methadone treatment (Metzger et al. 1993)
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MatchedCohort
Methadone VoluntaryDischarge
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0.150.85
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Death Rates in Treated and Untreated Heroin Addicts
Annu
al R
ate
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10,000
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Untreated Incarceration Adolescent Adult Methadone Drug Free
Residential Outpatient
$1,575$1,750
$8,250$9,825
$20,000$21,500No Treatment
In Treatment Program
Compare the CostsCosts are for a 6 month
period, per person
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
Adequate Dose and Duration
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
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Naltrexone: “Victimless Cure”
• One reason not to take naltrexone:
• Can’t get high!• “It’s like taking nothing”
• Limited Success:• Coercion or Bribery
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OH
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.
Buprenorphine: Pharmacological Characteristics
Partial Agonist (ceiling effect)
• high safety profile
• low dependence
Tight Receptor Binding• long duration of action
• slow onset mild abstinence
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Buprenorphine (mg)
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Buprenorphine (mg)
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Methadone (mg)
Opiate Agonist Measures VAS Good Drug Effect (0-100)
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buprenorphine (2mg)buprenorphine (2mg) and naloxone (1 mg)buprenorphine (2 mg) and naloxone (0.5 mg)buprenorphine (2 mg) and nalxone (0.25 mg)morphine (15 mg)placebo
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Adding Naloxone to Buprenorphine
Value of a Dose in Dollars
Dol
lars
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
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)
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Dose of Suboxone (Days 1-4)
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Symptoms Craving
• Treatment of HIV/AIDS: drug/drug interactions
• Flexibility in delivery• Role in treatment of pain
• 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
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
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
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, 2002Heroin death: five fold reductionPremature birth: 3-fold reduction
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.
Thank youthank you
thank you