Targeted Opioid Receptor Antagonists in the Treatment of Alcohol Use Disorders

Abstract

In 1994, the US Food and Drug Administration approved the μ-opioid receptor antagonist naltrexone to treat alcohol dependence. However, treatments requiring daily administration, such as naltrexone, are inconsistently adhered to in substance abusing populations, and constant medication exposure can increase risk of adverse outcomes, e.g., hepatotoxicity. This has fostered a ‘targeted’ or ‘as needed’ approach to opioid receptor antagonist treatment, in which medications are used only in anticipation of or during high-risk situations, including times of intense cravings. Initial studies of the ability of targeted naltrexone to reduce drinking-related outcomes were conducted in problem drinkers and have been extended into larger, multi-site, placebo-controlled investigations with positive results. Another μ-opioid receptor antagonist, nalmefene, has been studied on an ‘as-needed’ basis to reduce heavy drinking in alcohol-dependent individuals. These studies include three large multi-site trials in Europe of up to 1 year in duration, and serve as the basis for the recent approval of nalmefene by the European Medicines Agency as an ‘as-needed’ adjunctive treatment for alcohol dependence. We review potential moderators of opioid receptor antagonist treatment response including subjective assessments, objective clinical measures and genetic variants. In sum, the targeted or ‘as-needed’ approach to treatment with opioid antagonists is an efficacious harmreduction strategy for problem drinking and alcohol dependence.

Effects of naltrexone on alcohol self‐administration and craving: meta‐analysis of human laboratory studies

“…Studies in this review also diverge from RCTs in the exclusive use of acute or sub‐acute medication schedules. In this respect, the present results are potentially relevant for applications of short‐term opioid antagonist therapy to reduce acute alcohol craving and consumption (Niciu and Arias, 2013). Also noteworthy is that these analyses found no evidence that number of dosage days moderated effect sizes for craving or SA.…”

“…Finally, given the exclusive use of acute or sub‐acute medication schedules in human laboratory trials, these findings are potentially relevant for the efficacy of short‐term opioid antagonist treatments for reducing alcohol craving and consumption (e.g. Niciu and Arias, 2013). The present study applied meta‐analysis to evaluate the aggregate effects of naltrexone versus placebo on measures of laboratory SA and craving, with the primary aims of quantifying medication effects under experimental conditions and testing potential moderators of medication effects.…”

Nalmefene for the treatment of alcohol dependence: a current update

“…There is no evidence of significant activity at any other receptor type (for review see Niciu and Arias, 2013). Chronic nalmefene administration does not change dopamine receptor function, as shown by animal PET studies (Unterwald et al, 1997).…”

La terapia farmacologica dell'alcolismo: l'acamprosato e il nalmefene gli ultimi due farmaci anti-alcol approvati dagli organismi regolatori per la pratica clinica. Parte IV

“…Gli studi sulla capacità del naltrexone "al bisogno" di ridurre il consumo alcolico inizialmente condotti su bevitori problematici successivamente hanno dato risultati positivi anche in studi multisito controllati con placebo; il nalmefene è stato studiato sulla base dell'approccio "al bisogno" per ridurre il bere pesante in soggetti dipendenti da alcol; questi studi comprendono 3 ampi studi multisito fino a 1 anno di durata condotti in Europa che sono serviti come base per la recente approvazione (nel 2013) del nalmefene da parte dell'European Medicines Agency (EMA) come trattamento aggiuntivo "al bisogno" per la dipendenza da alcol. In complesso l'approccio terapeutico "al bisogno" del trattamento con antagonisti degli oppioidi è un efficace strategia di riduzione del danno per il bere problematico e per la dipendenza da alcol (Niciu & Arias, 2013). In un'update relativa alle numerose ricerche concernenti il coinvolgimento del sistema cerebrale degli oppioidi-endorfine nel mediare gli effetti di rinforzo dell'alcol è stato evidenziato che il naltrexone è efficace nel trattamento della dipendenza da alcol e che il nalmefene, recentemente approvato dall'EMA per il trattamento "al bisogno" dell'alcolismo, è pure efficace nel trattamento della dipendenza da alcol.…”