Adherence Monitoring in Naltrexone Pharmacotherapy Trials: A Systematic Review*

Brown University Alpert Medical School, Center for Alcohol and Addiction Studies, 121 South Main Street, Room 404, Providence, Rhode Island 02903, USA.
Journal of studies on alcohol and drugs (Impact Factor: 2.76). 11/2011; 72(6):1012-8. DOI: 10.15288/jsad.2011.72.1012
Source: PubMed


The efficacy of naltrexone (Revia, Vivitrol) for the treatment of alcohol dependence exhibits a high degree of heterogeneity. The aim of the current study was to evaluate the extent to which variability in patient adherence to treatment contributed to the range of clinical responses observed during naltrexone treatment.
A systematic review was conducted of efficacy trials of naltrexone for the treatment of alcohol dependence to evaluate the level of adherence monitoring.
Of 49 identified trials, 22 (49%) met the inclusion criteria of being randomized, double-blind, placebo-controlled trials that reported adherence. The "adherence-assurance score" of these trials was calculated as a function of the frequency with which "low," "moderate," or "high" confidence levels of adherence monitoring were used. Of these 22 randomized, controlled trials, only 3 (14%) met criteria for high levels of adherence assurance, 5 (23%) met medium adherenceassurance criteria, and 14 (64%) met low adherence criteria. Of the three high-assurance studies, one used direct supervision of thrice-weekly oral dosing of naltrexone, and two used extended-release injectable formulations of naltrexone administered once per month. The Spearman correlation between risk ratios for return to heavy drinking (for naltrexone vs. placebo) and the level of adherence assurance (low vs. medium vs. high) was significant (r = -.62, p = .025).
These findings suggest that the modest effect sizes for naltrexone reported in systematic reviews and meta-analyses may be attributable, at least in part, to variability in naltrexone adherence rates. High-assurance adherence strategies should be standard practice in clinical trials of medications being evaluated for the treatment of alcohol dependence.

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    • "Any systematic differences in attrition rates (e.g., more attrition among females, or among older patients) should also be reported, and variables associated with attrition should be considered as covariates in subsequent analyses (National Research Council, 2010). In addition, the level of adherence to the medication and the methods used to evaluate medication adherence, as well as attendance at behavioral treatment sessions, should be reported, with consideration given to their use as covariates (Baros et al., 2007; Stout et al., 2014; Swift et al., 2011). "
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    ABSTRACT: The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) are to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past 2 decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. This paper provides a narrative review of guidance on reporting quality in AUD treatment trials. Despite improvements in the reporting of results of treatment trials for AUD over the past 2 decades, many published reports provide insufficient information on design or methods. The reporting of alcohol treatment trial design, analysis, and results requires improvement in 4 primary areas: (i) trial registration, (ii) procedures for recruitment and retention, (iii) procedures for randomization and intervention design considerations, and (iv) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; 39(9). DOI:10.1111/acer.12797 · 3.21 Impact Factor
    • "In pharmacotherapy trials, fidelity is often indexed by adherence to medication, measured using self-report, pill counts, urinary riboflavin, electronic medication event monitoring systems, or monitoring of medication blood levels. The degree of medication adherence can have an impact on alcohol treatment outcomes (Baros et al., 2007; Stout et al., 2014), as can the quality of the adherence monitoring (Swift et al., 2011). Thus, adherence rates and monitoring method should always be reported (Witkiewitz et al., 2015). "
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    ABSTRACT: Over the past 60 years, the view that "alcoholism" is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders (AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and nonpharmacological interventions for AUDs. This paper provides a narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. Despite considerable improvements in the design of alcohol clinical trials over the past 2 decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; 39(9). DOI:10.1111/acer.12800 · 3.21 Impact Factor
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    • "Nonetheless , naltrexone is an FDA-approved treatment for AUDs and is reported to reduce the number of heavy drinking days (Jonas et al., 2014). However, it is not effective in all patients, and there are substantial patient compliance issues (Swift et al., 2011). Opioid receptor-based medications with more selective mechanisms of action, based on a refined understanding of the neurobiological basis of excessive drinking, are still needed. "
    Alcoholism Clinical and Experimental Research 04/2015; 39(4):575-8. DOI:10.1111/acer.12668 · 3.21 Impact Factor
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