Buprenorphine in the treatment of opioid dependence

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Abstract

Buprenorphine has become of increasing interest to be an alternative to methadone in the treatment of heroin addicts. The aim of the paper is to review, from a clinical perspective, the current status of what is known about the pharmacology of buprenorphine, with a particular emphasis on the issues of maintenance therapy in heroin addiction. A systematic review of published follow-up data, from observational and experimental studies was done. Electronic databases Medline and PSYNDEXplus were searched from their earliest entries. Buprenorphine appears to be a well-tolerated drug, with a benign overall side effect. Buprenorphine is an additional treatment option for heroin dependent patients, especially for those who do not wish to start or continue with methadone or for those who do not seem to benefit from adequate dosages of methadone.

Introduction

Substitution for opioid addicts has established itself as an effective medical therapy over the past years. Scientific examinations have been able to demonstrate that this form of treatment leads to a reduction in the consumption of opioids and a reduction in the higher rate of mortality and morbidity Segest et al., 1990, Kreek et al., 2002. Moreover, an improvement in the social situation of the persons affected, a reduction in drug-related crimes and a reduction in the transmission rate of HIV could also be achieved Senay, 1985, Metzger et al., 1993.

Methadone has up to now been the standard substance in the substitution therapy of opioid addicts (O'Connor and Fiellin, 2000). This is a pure μ-opioid receptor agonist with the corresponding pharmacological properties. New possibilities have arisen with respect to a differentiated therapy through the availability of new substances such as buprenorphine and levacetylmethadol (LAAM) for the substitution treatment of patients addicted to opioids Krook et al., 2002, Law and Nutt, 2003, Ling et al., 1994, O'Connor et al., 1996. Buprenorphine was first suggested by Jasinski et al. (1978) as an alternative in the oral substitution therapy of opiate addicts. This article will discuss the pharmacology and clinical applicability of buprenorphine in both substitution and detoxification of opioid dependence. A systematic review of published follow-up data, from observational and experimental studies was done. Electronic databases Medline and PSYNDEXplus were searched from their earliest entries.

Section snippets

Pharmacokinetics

When planning therapeutic approaches to opiate addiction it is very important that injectable forms of administration be avoided. This can reduce the spread of infectious diseases such as HIV, hepatitis and other parenterally transferred infections. On account of its intestinal and hepatic metabolism, buprenorphine has a very low oral bioavailability. The successful development of a sublingual pain tablet proves the acceptance of this form of application. In the majority of clinical studies,

Dose finding studies and safety profile

In initial studies with buprenorphine, it could be shown that taking into account the different target parameters, buprenorphine is suitable for substitution therapy Jasinski et al., 1982, Jasinski et al., 1984, Johnson et al., 1989. The buprenorphine dose needed to suppress the opiate consumption is above 4 mg/day according to the results of the studies. The ratio of the dose to the extent of the bioavailability (AUC) is proportionate to the dose in the dosage range between 2 and 16 mg

Controlled studies of buprenorphine versus placebo in maintenance treatment

In a random, double-blind study with a comparison of parallel groups, sublingual buprenorphine was compared with a placebo (Johnson et al., 1995). Randomisation was carried out at the ratio 2:2:1 for placebo, buprenorphine 2 or 8 mg. This test was based on the assumption that a higher dose of buprenorphine causes a greater effect if all participants in the test take their allocated dose up to and including day 6. Between days 6 and 13, the test persons were then given the option of receiving an

Studies of managed withdrawal

Whereas the maintenance therapy is an important stabilising factor in the treatment of drug addiction, a withdrawal treatment should be seen as the ultimate goal as regards the abstinence and drug-free life of patients Gowing et al., 2002, Lintzeris et al., 2002.

Sublingually administered buprenorphine was compared with clonidine within the scope of a temporary withdrawal of patients addicted to heroin (Cheskin et al., 1994). In these studies that ran for 10 days buprenorphine was administered

Switch from methadone to buprenorphine

A few studies investigated the possibility of switching from methadone to buprenorphine. One study is worth mentioning in this context in which it proved easy to adjust to buprenorphine (4 mg/day) 24–26 h after the last dose following an abrupt discontinuation of methadone (which was titrated down before the abrupt switching to 20–30 mg/day) (Law et al., 1997). These results correspond with other studies (Levin et al., 1997) and confirm that a rapid change in therapy from methadone to

Undesirable effects of buprenorphine

The good safety profile of buprenorphine that was indicated in preclinical studies, could be confirmed in the numerous clinical studies that have been carried out. The range of undesirable effects corresponds to the expected side effects under other opiates. In a study that was performed expressly to investigate these criteria the only side effects of a buprenorphine treatment that were listed were a correlation between sedation and constipation (Lange et al., 1990). The evaluation of the

Opioid addiction and pregnancy

The efficacy of a substitution treatment for pregnant women with an opioid addiction is taken as assured. On the other hand, a Neonatal Abstinence Syndrome (NAS) is often observed under a substitution with methadone (Finnegan, 1991). In principle, there is not enough data on buprenorphine in this context to allow a general recommendation. With respect to an NAS, several studies have provided clues for advantages over a substitution with methadone Fischer et al., 1998, Fischer et al., 2000, Eder

Summary

The goal of the treatment is to stabilise patients as quickly as possible with an adequate buprenorphine dosage to prevent the occurrence of withdrawal symptoms. As regards the overall success of the treatment, this is very important with regard to the satisfaction of the patients and thus the motivation for the individual to continue the therapy. In any case, it should be clarified if and which co-medication the patient is taking (significant, e.g. with antiviral drugs). The first

References (101)

  • F.D. Law et al.

    Maintenance buprenorphine for opioid users

    Lancet

    (2003)
  • W. Ling et al.

    Clinical efficacy of buprenorphine: comparisons to methadone and placebo

    Drug Alcohol Depend.

    (2003)
  • N.K. Mello et al.

    Buprenorphine self-administration by rhesus monkey

    Pharmacol. Biochem. Behav.

    (1981)
  • D.J. Nutt

    Addiction: brain mechanisms and their treatment implications

    Lancet

    (1996)
  • S. Petitjean et al.

    Double-blind randomized trial of buprenorphine and methadone in opiate dependence

    Drug Alcohol Depend.

    (2001)
  • S.E. Robinson

    Effects of perinatal buprenorphine and methadone exposures on striatal cholinergic ontogeny

    Neurotoxicol. Teratol.

    (2002)
  • R. Rosenheck et al.

    Buprenorphine for opiate addiction: potential economic impact

    Drug Alcohol Depend.

    (2001)
  • R.S. Schottenfeld et al.

    Buprenorphine: dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans

    Biol. Psychiatry

    (1993)
  • R.S. Schottenfeld et al.

    Thrice-weekly versus daily buprenorphine maintenance

    Biol. Psychiatry

    (2000)
  • A.E. Takemori et al.

    The mu, kappa and delta properties of various opioid agonists

    Eur. J. Pharmacol.

    (1986)
  • S.L. Walsh et al.

    The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic

    Drug Alcohol Depend.

    (2003)
  • L. Amass et al.

    A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification

    J. Addict. Dis.

    (1994)
  • P.G. Barnett et al.

    A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence

    Addiction

    (2001)
  • P.G. Barnett et al.

    The cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States

    Addiction

    (2001)
  • W.K. Bickel et al.

    Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans

    J. Pharmacol. Exp. Ther.

    (1988)
  • W.K. Bickel et al.

    Effects of adding behavioral treatment to opioid detoxification with buprenorphine

    J. Consult. Clin. Psychol.

    (1997)
  • J.A. Bodkin et al.

    Buprenorphine treatment of refractory depression

    J. Clin. Psychopharmacol.

    (1995)
  • S.D. Comer et al.

    Self-administration of intravenous buprenorphine and the buprenorphine/naloxone combination by recently detoxified heroin abusers

    J. Pharmacol. Exp. Ther.

    (2002)
  • P.A. Compton et al.

    Buprenorphine as a pharmacotherapy for cocaine abuse: a review of the evidence

    J. Addict. Dis.

    (1995)
  • E.J. Cone et al.

    Toxicologic aspects of heroin substitution treatment

    Ther. Drug Monit.

    (2002)
  • A. Cowan et al.

    Agonist and antagonist properties of buprenorphine, a new antinociceptive agent

    Br. J. Pharmacol.

    (1977)
  • K. Diamant et al.

    Outpatient opiate detoxification treatment with buprenorphine. Preliminary investigation

    Eur. Addict. Res.

    (1998)
  • H. Eder et al.

    Buprenorphin in der Schwangerschaft

    Psychiatr. Prax.

    (2001)
  • H.M. Emrich et al.

    Possible antidepressive effects of opioids: action of buprenorphine

    Ann. N.Y. Acad. Sci.

    (1982)
  • D.A. Fiellin et al.

    Treatment of heroin dependence with buprenorphine in primary care

    Am. J. Drug Alcohol Abuse

    (2002)
  • L.P. Finnegan

    Treatment issues for opioid-dependent women during the perinatal period

    J. Psychoact. Drugs

    (1991)
  • G. Fischer et al.

    Buprenorphine maintenance in pregnant opiate addicts

    Eur. Addict. Res.

    (1998)
  • G. Fischer et al.

    Vergleichsuntersuchung von Buprenorphin und Methadon im Rahmen der Erhaltungstherapie Opiatkranker

    Nervenarzt

    (1999)
  • G. Fischer et al.

    Treatment of opioid-dependent pregnant women with buprenorphine

    Addiction

    (2000)
  • M.T. French

    Cost-effectiveness of buprenorphine maintenance versus methadone maintenance

    Addiction

    (2001)
  • G. Gonzalez et al.

    Treatment of heroin (diamorphine) addiction: current approaches and future prospects

    Drugs

    (2002)
  • L. Gowing et al.

    Buprenorphine for the management of opioid withdrawal

    Cochrane Database Syst. Rev.

    (2002)
  • P.N. Gueye et al.

    Trends in opiate and opioid poisonings in addicts in north-east Paris and suburbs, 1995–1999

    Addiction

    (2002)
  • D.R. Jasinski et al.

    Human pharmacology and abuse potential of the analgesic buprenorphine

    Arch. Gen. Psychiatry

    (1978)
  • D.R. Jasinski et al.

    Progress report of the NIDA Addiction Research Center

    NIDA Res. Monogr.

    (1982)
  • D.R. Jasinski et al.

    Progress report from the NIDA Addiction Research Center, Baltimore, Maryland

    NIDA Res. Monogr.

    (1984)
  • D.R. Jasinski et al.

    Sublingual versus subcutaneous buprenorphine in opiate abusers

    Clin. Pharmacol. Ther.

    (1989)
  • R.E. Johnson et al.

    Buprenorphine and naloxone for heroin dependence

    Curr. Psychiatry Rep.

    (2000)
  • R.E. Johnson et al.

    Use of buprenorphine in the treatment of opiate addiction: I. Physiologic and behavioral effects during a rapid dose induction

    Clin. Pharmacol. Ther.

    (1989)
  • R.E. Johnson et al.

    A controlled trial of buprenorphine treatment for opioid dependence

    JAMA

    (1992)

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