New trends in opiate pharmacotherapy

FRANÇAIS :
Les différentes modalités thérapeutiques proposées pour les traitements de substitution des personnes dépendantes aux opiacés sont analysées à partir des principales études internationales. Si la méthadone et la buprénorphine sont les plus connues, le LAAM , la lofexidine et le sevrage ultra-rapide par la naltrexone sont ausi abordés. Les comparaisons portent sur la biodisponibilité, l'efficacité, les effets secondaires et contre-indications et les compléments nécessaires en matière de soutien psychothérapique.
ENGLISH:
Clinical observation and controlled clinical trials have established the safety -and efficacy of buprenorphine. Sublingual tablets alone, or with the addition of naloxone, which appears to reduce abuse potential, have been shown to produce comparable clinical effects at appropriate doses and to be acceptable to patients. The bioavailability of the tablet formulation has proved in chronic dosing to be comparable to the liquid formulation used in earlier clinical trials, validating those results. A number of dosing strategies, ranging from multiple times daily to several times weekly appear feasible. Used in pregnancy, buprenorphine appears to result in healthy infants with minimal signs of neonatal withdrawal. Finally, the therapeutic effects of buprenorphine can be enhanced with behavioral therapy which, from early experience in general medical settings, appears both possible and practical. LAAM, available since 1993, is slowly gaining acceptance as an opiate pharmacotherapy, but remains grossly underutilized due largely to regulatory hurdles related to its clinical implementation. Recent studies have clarified some aspects of LAAM's clinical pharmacology but should not alter the basic guidelines governing its clinical use. LAAM should rightly be viewed not as an alternative, but as an addition to methadone. There are no clear-cut indications at present for patient selection to either LAAM or methadone except that those patients whose medication fails to 'hold' at high doses may do better with LAAM. Pharmacologically, there is no reason for the prohibition of LAAM take-home doses. Data remain sparse on the effect of LAAM on cardiac conduction, on its use in pregnancy, and for patients under 18 years of age. The major recent effort relating to methadone treatment has concentrated on its delivery, although studies in a number of countries have reaffirmed its clinical effectiveness in reducing heroin use and improving patient health. Unresolved clinical issues include those of adequate dose and duration of treatment. Lofexidine appears similar to clonidine in its ability to moderate symptoms of opiate withdrawal, but with fewer hypotensive effects. Its place in opiate pharmacotherapy must be viewed in the context of the overall utility of short-term detoxification as a long-term treatment strategy. Finally, despite its enthusiasts, UROD remains largely untested and cannot be unconditionally endorsed. (Author's abstract.)