Meta‐analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?

Abstract

Aims Although debates over the efficacy of oral naltrexone and acamprosate in treating alcohol use disorders tend to focus on their global efficacy relative to placebo or their efficacy relative to each other, the underlying reality may be more nuanced. This meta-analysis examined when naltrexone and acamprosate are most helpful by testing: (1) the relative efficacy of each medication given its presumed mechanism of action (reducing heavy drinking versus fostering abstinence) and (2) whether different ways of implementing each medication (required abstinence before treatment, detoxification before treatment, goal of treatment, length of treatment, dosage) moderate its effects. Methods A systematic literature search identified 64 randomized, placebo-controlled, English-language clinical trials completed between 1970 and 2009 focused on acamprosate or naltrexone. Results Acamprosate had a significantly larger effect size than naltrexone on the maintenance of abstinence, and naltrexone had a larger effect size than acamprosate on the reduction of heavy drinking and craving. For naltrexone, requiring abstinence before the trial was associated with larger effect sizes for abstinence maintenance and reduced heavy drinking compared to placebo. For acamprosate, detoxification before medication administration was associated with better abstinence outcomes compared to placebo. Conclusions In treatment for alcohol use disorders, acamprosate has been found to be slightly more efficacious in promoting abstinence and naltrexone slightly more efficacious in reducing heavy drinking and craving. Detoxification before treatment or a longer period of required abstinence before treatment is associated with larger medication effects for acamprosate and naltrexone, respectively.

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

“…The advantages of laboratory paradigms include the ability to quantify objective measures of behavior, examine genetic moderators under controlled conditions and isolate theoretical mediators of pharmacotherapy effects (Perkins and Lerman, 2011; Plebani et al , 2012; Ray et al , 2010). In principle, lower heterogeneity in effect sizes can be expected in the context of controlled laboratory trials; of note, measures of heterogeneity in this analysis appeared relatively lower than those reported in other meta‐analyses (Maisel et al , 2013; Rösner et al , 2010). The additional possibility of larger effect sizes under experimental conditions is an additional argument for laboratory‐based medication screening trials, which can provide a cost‐efficient means of medication screening (McKee, 2009; Perkins and Lerman, 2011).…”

“…This effect was modest ( g  = −.277) but reliable, with minimal heterogeneity observed across studies. By comparison, effect sizes for heavy drinking or drinking quantity outcomes across randomized clinical trials generally range between g  = .10 and .20 (Jonas et al , 2014; Maisel et al , 2013; Rösner et al , 2010). Thus, a modest effect on laboratory SA is consistent with what is known about naltrexone's effects on self‐reported drinking quantity during longer periods of treatment.…”

“…A prior meta‐analysis found no differences in craving between naltrexone and placebo groups during treatment periods lasting up to three months (Srisurapanont and Jarusuraisin, 2005). In a more recent meta‐analysis, results from 26 RCTs suggested a small but significant medication effect ( g  = .14) on craving (Maisel et al , 2013). Relatively smaller (or non‐significant) medication effects in RCT meta‐analyses may reflect the use of retrospective craving reports that span days or weeks.…”

“…If studies reported more than one SA outcome, we coded the primary outcome. One study used a within‐subjects design without sufficient data to establish a pre‐to‐post correlation for the SA outcome; we imputed this value by estimating a moderate correlation ( r  = .50), similar to procedures reported in another meta‐analysis of naltrexone (Maisel et al , 2013). …”

“…Meta‐analyses support that, as an adjunct to psychosocial therapy, daily naltrexone reduces the number of drinking days, quantity of alcohol consumed and incidence of relapse to heavy drinking relative to placebo—albeit with modest effect sizes (Jonas et al , 2014; Maisel et al , 2013; Rösner et al , 2010). Meta‐analyses further indicate relatively greater efficacy of naltrexone versus acamprosate for reducing heavy drinking and craving (Maisel et al , 2013). Nonetheless, naltrexone remains significantly under‐utilized in clinical practice (Heilig et al , 2011; Heilig, 2015).…”