Background and AimsStudies of the efficacy of gabapentin for treating alcohol use disorder (AUD) have yielded mixed findings. The aims of our study were to estimate gabapentin's effects on six alcohol‐related outcomes, test potential moderators, examine publication bias and evaluate the quality of the studies.MethodsMeta‐analysis of placebo‐controlled randomized controlled trials (RCTs). Using PubMed and ClinicalTrials.gov, we selected RCTs of gabapentin's effects on alcohol consumption or a biochemical correlate of it, excluding studies limited to other primary outcomes or that combined gabapentin with other medications. We assessed study quality and used a random‐effects model to analyze each outcome measure and the Egger regression test and funnel plots to assess publication bias.ResultsWe identified seven RCTs of gabapentin that met study criteria. The quality of the studies overall was good, and there was no evidence of publication bias. Four to seven studies contributed to the analysis of the six outcome measures. For all outcome measures the effect estimates were in a direction that favored gabapentin over placebo. However, only for percentage of heavy drinking days was there good evidence of a benefit (g = −0.64, 95% confidence interval = −1.22 to −0.06).ConclusionsAlthough gabapentin appears to be more efficacious than placebo in treating AUD, the only measure on which the analysis clearly favors the active medication is percentage of heavy drinking days. Additional studies are needed to define more clearly the role of gabapentin in AUD treatment.
In a prior study, topiramate reduced heavy drinking among individuals who sought to reduce their drinking, with the effect moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit (Kranzler et al. 2014). The present study sought to replicate prospectively the effect of topiramate and rs2832407 in patients with DSM-5 alcohol use disorder (AUD) who sought to reduce or stop their drinking. We stratified the randomization on genotype (rs2832407*C-allele homozygotes vs. A-allele carriers) and assigned 170 European-American participants (71.2% male) to receive 12 weeks of treatment with topiramate (N = 85), at a maximal daily dosage of 200 mg, or matching placebo (N = 85). At each of nine treatment visits participants received brief counseling to reduce drinking and increase abstinent days. We hypothesized that topiramate-treated patients with the rs2832407*CC genotype would reduce heavy drinking days (HDDs) more than the other three groups. The rate of treatment completion was 91.8% in both groups. The mean number of HDDs per week in the placebo group was 1.67 (95% CI = (1.29, 2.16), p = 0.0001) times greater than in the topiramate group, which was confirmed by the topiramate group’s significantly greater reduction in the concentration of the liver enzyme γ-glutamyltransferase and lower alcohol-related problems score. There was no significant difference in topiramate’s effect on HDDs between genotype groups. Although consistent with other studies showing a reduction in heavy drinking with topiramate treatment, the prior finding of a moderating effect of rs2832407 genotype was not replicated in this prospective trial.
Background and AimsThere is wide inter‐individual variability in response to the treatment of alcohol use disorder (AUD) with the opioid receptor antagonist naltrexone. To identify patients who may be most responsive to naltrexone treatment, studies have examined the moderating effect of rs1799971, a single nucleotide polymorphism (SNP) that encodes a non‐synonymous substitution (Asn40Asp) in the mu‐opioid receptor gene, OPRM1. The aims of this study were to: (1) conduct a systematic review of randomized clinical trials (RCTs); (2) assess the bias of the available studies and gauge publication bias; and (3) meta‐analyze the interaction effect of the Asn40Asp SNP on the response to naltrexone treatment.MethodsWe searched for placebo‐controlled RCTs that examined the effect of Asn40Asp on the response to naltrexone treatment of heavy drinking or AUD. We tested the hypothesis that the minor (Asp40) allele was associated with a greater reduction in five alcohol consumption measures (relapse to heavy drinking, abstinence, percentage of heavy drinking days, percentage of days abstinent and drinks per day) in naltrexone‐treated participants by meta‐analyzing the interaction effects using a random effects model.ResultsSeven RCTs met the study criteria. Overall, risk of bias was low and we observed no evidence of publication bias. Of the five alcohol consumption outcomes considered, there was a nominally significant moderating effect of the Asn40Asp SNP only on drinks per day (d = −0.18, P = 0.02). However, the effect was not significant when multiple comparisons were taken into account.ConclusionsFrom the evidence to date, it remains unclear whether rs1799971, the OPRM1 Asn40Asp single nucleotide polymorphism, predicts naltrexone treatment response in individuals with alcohol use disorder or heavy drinking.
Objectives: Several medications have been shown to be safe and effective for treating alcohol use disorder (AUD); however, these medications are prescribed infrequently. We conducted a survey of the demographics, practice characteristics, and self-perceived knowledge, experience, and opinions of addiction specialists on the use of AUD medications and how to increase their use. Methods:We sent a 19-question survey to members of the American Society of Addiction Medicine (ASAM) and the American Academy of Addiction Psychiatry (AAAP). Results:We received a total of 395 responses from ASAM members and 194 responses from AAAP members. One hundred of the respondents were members of both organizations. The large majority of respondents (92.6%) were prescribers, and 81.6% were non-trainee physicians. The two most frequently used medications for treating AUD were oral naltrexone (27%) and long-acting naltrexone (18%). Respondents were significantly more confident in the strength of the research findings and evidence for the efficacy and safety of naltrexone than other AUD medications (p < 0.001 ). Respondents identified additional education to current providers about existing medications as the most important potential intervention to increase the use of AUD medications. Conclusions:Compared with a survey published in 2001, in 2018 the proportion of respondents who reported using naltrexone more than doubled and addiction specialists were more confident in their use of AUD medications, rating their efficacy and safety more highly. Consistent with findings from other recent studies, providing more education to practitioners about existing AUD medications may be the most effective way to increase their use.
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