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Pharmacotherapies and personalized medicine for alcohol use disorder: a review.

ABSTRACT: Alcohol use disorder (AUD) is highly prevalent and among the leading causes of morbidity and mortality in the United States. Pharmacotherapies for AUD are limited, thus making identification of patient subgroups that are most likely to respond favorably crucial. In this article, pharmacogenetic research on US FDA-approved and commonly prescribed off-label medications for the treatment of AUD is comprehensively reviewed. While the field has advanced in understanding pharmacotherapies for AUD and potential genetic moderators of treatment responses, the pharmacogenetic data to guide the prescribing clinician are limited and should be interpreted with caution. Precision medicine for AUD with more beneficial treatment responses and minimal side effects remains a high priority for further research.

SUBMITTER: Lohoff FW

PROVIDER: S-EPMC7586357 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Pharmacotherapies and personalized medicine for alcohol use disorder: a review.

Lohoff Falk W FW

Pharmacogenomics 20200818 15

Alcohol use disorder (AUD) is highly prevalent and among the leading causes of morbidity and mortality in the United States. Pharmacotherapies for AUD are limited, thus making identification of patient subgroups that are most likely to respond favorably crucial. In this article, pharmacogenetic research on US FDA-approved and commonly prescribed off-label medications for the treatment of AUD is comprehensively reviewed. While the field has advanced in understanding pharmacotherapies for AUD and ...[more]

PMID: 32807012

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Project description:ObjectiveNumerous behavioral treatments for alcohol use disorder (AUD) are effective, but there are substantial individual differences in treatment response. This study examines the potential use of new methods for personalized medicine to test for individual differences in the effects of cognitive behavioral therapy (CBT) versus motivational enhancement therapy (MET) and to provide predictions of which will work best for individuals with AUD. We highlight both the potential contribution and the limitations of these methods.MethodWe performed secondary analyses of abstinence among 1,144 participants with AUD participating in either outpatient or aftercare treatment who were randomized to receive either CBT or MET in Project MATCH. We first obtained predicted individual treatment effects (PITEs), as a function of 19 baseline client characteristics identified a priori by MATCH investigators. Then, we tested for the significance of individual differences and examined the predicted individual differences in abstinence 1 year following treatment. Predictive intervals were estimated for each individual to determine if they were 80% more likely to achieve abstinence in one treatment versus the other.ResultsResults indicated that individual differences in the likelihood of abstinence at 1 year following treatment were significant for those in the outpatient sample, but not for those in the aftercare sample. Individual predictive intervals showed that 37% had a better chance of abstinence with CBT than MET, and 16% had a better chance of abstinence with MET. Obtaining predictions for a new individual is demonstrated.ConclusionsPersonalized medicine methods, and PITE in particular, have the potential to identify individuals most likely to benefit from one versus another intervention. New personalized medicine methods play an important role in putting together differential effects due to previously identified variables into one prediction designed to be useful to clinicians and clients choosing between treatment options. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Project description:ObjectiveThis study aimed to determine the efficacy and acceptability of pharmacotherapies for cannabis use disorder (CUD).MethodsWe conducted a systematic review and frequentist network meta-analysis, searching five electronic databases for randomized placebo-controlled trials of individuals diagnosed with CUD receiving pharmacotherapy with or without concomitant psychotherapy. Primary outcomes were the reduction in cannabis use and retention in treatment. Secondary outcomes were adverse events, discontinuation due to adverse events, total abstinence, withdrawal symptoms, cravings, and CUD severity. We applied a frequentist, random-effects Network Meta-Analysis model to pool effect sizes across trials using standardized mean differences (SMD, g) and rate ratios (RR) with their 95% confidence intervals.ResultsWe identified a total of 24 trials (n=1912, 74.9% male, mean age 30.2 years). Nabilone (d=-4.47 [-8.15; -0.79]), topiramate (d=-3.80 [-7.06; -0.54]), and fatty-acid amyl hydroxylase inhibitors (d=-2.30 [-4.75; 0.15]) reduced cannabis use relative to placebo. Dronabinol improved retention in treatment (RR=1.27 [1.02; 1.57]), while topiramate worsened treatment retention (RR=0.62 [0.42; 0.91]). Gabapentin reduced cannabis cravings (d=-2.42 [-3.53; -1.32], while vilazodone worsened craving severity (d=1.69 [0.71; 2.66]. Buspirone (RR=1.14 [1.00; 1.29]), venlafaxine (RR=1.78 [1.40; 2.26]), and topiramate (RR=9.10 [1.27; 65.11]) caused more adverse events, while topiramate caused more dropouts due to adverse events.ConclusionsBased on this review, some medications appeared to show promise for treating individual aspects of CUD. However, there is a lack of robust evidence to support any particular pharmacological treatment. There is a need for additional studies to expand the evidence base for CUD pharmacotherapy. While medication strategies may become an integral component for CUD treatment one day, psychosocial interventions should remain the first line given the limitations in the available evidence.

Project description:BackgroundWe aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders.MethodsWe searched eleven electronic data sources for randomized clinical trials with at least 4 weeks of treatment reporting on alcohol consumption (total abstinence and reduced heavy drinking), dropouts, and dropouts due to adverse events. We conducted network meta-analyses using random-effects, frequentist models, and calculated summary rate ratios (RRs) with 95% confidence intervals (CIs).ResultsWe included 156 trials (N = 27,334). Nefazodone (RR = 2.11; 95% CI, 1.42-3.13), aripiprazole (RR = 1.97; 95% CI, 1.36-2.88), carbamazepine (RR = 1.85; 95% CI, 1.03-3.32), and nalmefene (RR = 1.17; 95% CI, 1.01-1.35) were associated with the most dropouts. Baclofen (RR = 0.83; 95% CI, 0.70-0.97) and pregabalin (RR = 0.63; 95% CI, 0.43-0.94) caused fewer dropouts than placebo. Nalmefene (RR = 3.26; 95% CI, 2.34-4.55), fluvoxamine (RR = 3.08; 95% CI, 1.59-5.94), and topiramate (RR=2.18; 95% CI, 1.36-3.51) caused more dropouts from adverse events over placebo. Gamma-hydroxy-butyrate (RR = 1.90; 95% CI, 1.03-3.53), baclofen (RR = 1.80; 95% CI, 1.39-2.34), disulfiram (RR = 1.71; 95% CI, 1.39-2.10), gabapentin (RR = 1.66; 95% CI, 1.04-2.67), acamprosate (RR = 1.33; 95% CI, 1.15-1.54), and oral naltrexone (RR = 1.15; 95% CI, 1.01-1.32) improved total abstinence over placebo (Fig. 3C). For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10-0.35), baclofen (RR = 0.72; 95% CI, 0.57-0.91), acamprosate (RR = 0.78; 95% CI, 0.70-0.86), and oral naltrexone (RR = 0.81; 95% CI, 0.73-0.90) were efficacious against placebo.ConclusionsThe current meta-analyses provide evidence that several medications for AUDs are effective and safe and encourage the expanded use of these medications in the clinical setting. Our review found that acamprosate (2-3 g/d), disulfiram (250-500 mg/d), baclofen (30 mg/d), and oral naltrexone (50 mg/d) had the best evidence for improving abstinence and heavy drinking for patients with AUD.ProsperoCRD42020208946.

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Pharmacotherapies and personalized medicine for alcohol use disorder: a review.

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Pharmacotherapies and personalized medicine for alcohol use disorder: a review.

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