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, 2009lwalter@ucla.edu

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

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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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HIV infection rates in and out of methadone treatment (Metzger et al. 1993)

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Death Rates in Treated and Untreated Heroin Addicts

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Untreated Incarceration Adolescent Adult Methadone Drug Free

Residential Outpatient

$1,575$1,750

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$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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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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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

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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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• 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