Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review.
ABSTRACT 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.
SourceAvailable from: Susan E Collins[Show abstract] [Hide abstract]
ABSTRACT: Background: Abstinence-based alcohol interventions are minimally desirable to and effective for chronically homeless individuals with alcohol dependence who have multimorbidity and high publicly funded service utilization and associated costs. Lower-barrier, patient-centered combined pharmacobehavioral interventions may more effectively treat this population. Harm reduction counseling involves a nonjudgmental, empathic style and patient-driven goal setting that requires neither abstinence nor use reduction. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving, is safe and effective for active drinkers, and may thereby support harm reduction goal setting. The aims of this 12-week, single-arm pilot were to initially document some aspects of feasibility, acceptability, and alcohol outcomes following XR-NTX administration and harm reduction counseling for chronically homeless individuals with alcohol dependence. Methods: Participants were currently/formerly chronically homeless, alcohol-dependent individuals (N = 31) from 2 community-based agencies in the US Pacific Northwest. Measures included self-reported alcohol craving, quantity/frequency, problems, and biomarkers (ethyl glucuronide [EtG], liver transaminases). XR-NTX and harm reduction counseling were administered monthly over the 3-month treatment course. Results: Of the 45 individuals approached, 43 were interested in participation. The first injection was received by 31 participants, and 24 complied with all study procedures. Participants reported the treatment was acceptable. Participants evinced decreases in alcohol craving (33%), typical (25%) and peak (34%) use, frequency (17%), problems (60%), and EtG from the baseline to the 12-week follow-up (Ps Conclusions: XR-NTX and harm reduction counseling are promising means of supporting reductions in alcohol use and alcohol-related harm among chronically homeless, alcohol-dependent individuals.Substance Abuse 04/2014; 36(1). DOI:10.1080/08897077.2014.904838 · 1.62 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: AimsWe use intensive longitudinal data methods to illuminate processes affecting patients’ drinking in relation to the discontinuation of medications within an alcohol treatment study. Although previous work has focused on broad measures of medication adherence, we focus on dynamic changes in drinking both before and after patients discontinue.DesignWe conducted secondary data analyses using the COMBINE study, focused on participants who discontinued medications prior to the planned end of treatment. Using an interrupted timeseries analysis, we analyzed drinking in the weeks before and after discontinuation and also studied outcomes at the end of the COMBINE follow-up.SettingUnites States of America.ParticipantsWe describe the sub-sample of COMBINE participants who discontinued medications (n=450), and compare them with those who were medication adherent (n=559) and with those who discontinued but had substantial missing data (n=217).MeasurementsThe primary outcomes were percent days abstinent (PDA) and percent heavy drinking days (PHDD). Medication adherence data were used to approximate the date of discontinuation.FindingsFor many patients, an increase in drinking began weeks before discontinuation (PDA: F(1,4803) = 19.07, p < .001; PHDD: F(1,4804) = 8.58, p = .003) then escalated at discontinuation (PDA: F(1,446) = 5.05, p = .025; PHDD: F(1,446) = 4.52, p = .034). Among other effects, the amount of change was moderated by the reason for discontinuation (e.g., adverse event; PDA: F(2,4803) = 3.85, p = .021; PHDD: F(2,4804) = 5.36, p = .005) and also whether it occurred in the first or second half of treatment (PDA: F(1,4803) = 5.23, p = .022; PHDD: F(1,4804) = 8.79, p = .003).ConclusionsA patient's decision to stop taking medications during alcohol treatment appears to take place during a weeks-long process of disengagement from treatment. Patients who discontinue medications early in treatment or without medical consultation appear to drink more frequently and more heavily.Addiction 08/2014; 109(12). DOI:10.1111/add.12700 · 4.60 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Reduction of alcohol consumption is not yet a widely accepted treatment objective for alcohol-dependent patients, as abstinence is often considered to be the only possible objective in this situation. However, various studies have demonstrated the value of proposing these two options to such patients. Firstly, reduction of alcohol consumption very significantly reduces the risk of alcohol-related damage, and also modifies the patient's and the doctor's perception of the disease, resulting in improved access to care and better patient adherence with the proposed treatment objective and consequently better clinical results. Recent studies have shown that some medicinal products can help patients reduce their alcohol consumption. One such product, nalmefene, has been granted European marketing authorization and is now being released onto the market in various countries. The ESENSE 1 and 2 studies in alcohol-dependent patients showed that, in combination with BRENDA, a psychosocial intervention focusing on reinforcement of motivation and treatment adherence, nalmefene significantly reduced the number of heavy drinking days and mean daily total alcohol consumption versus placebo. This reduction was more marked in the marketing authorization target population, ie, patients with a high or very high drinking risk level according to World Health Organization criteria. Another original feature of this molecule is that it can be used as needed if the patient perceives a risk of drinking, which is a more flexible approach and more likely to ensure the patient's active involvement in the treatment of his/her disease. This molecule opens up interesting and original therapeutic prospects in the treatment of alcohol dependence.08/2014; 5:87-94. DOI:10.2147/SAR.S45666