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Advancing Precision Medicine for Alcohol Use Disorder: Replication and Extension of Reward Drinking as a Predictor of Naltrexone Response
Author(s) -
Witkiewitz Katie,
Roos Corey R.,
Mann Karl,
Kranzler Henry R.
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14183
Subject(s) - naltrexone , placebo , moderation , psychology , heavy drinking , clinical psychology , randomized controlled trial , alcohol use disorder , medicine , alcohol , poison control , injury prevention , social psychology , antagonist , environmental health , alternative medicine , biochemistry , chemistry , receptor , pathology
Background Precision medicine aims to identify those patients who will benefit the most from specific treatments. Recent work found large effects of naltrexone among “reward drinkers,” defined as individuals who drink primarily for the rewarding effects of alcohol. This study sought to replicate and extend these recent findings by examining whether the desire to drink mediated the effect of naltrexone among reward drinkers. Methods We conducted a secondary analysis of a 12‐week randomized clinical trial of daily or targeted naltrexone among problem drinkers ( n = 163), with a focus on 86 individuals ( n = 45 naltrexone and n = 41 placebo) who received daily medication. Interactive voice response technology was used to collect daily reports of drinking and desire to drink. Factor mixture models were used to derive reward and relief phenotypes. Moderation analyses were used to evaluate naltrexone effects, with phenotype as a moderator variable. Multilevel mediation tested average desire to drink as a mediator. Results Results indicated 4 phenotypes: low reward/low relief; low reward/high relief; high reward/low relief; and high reward/high relief. There was an interaction between the high reward/low relief subgroup ( n = 10) and daily naltrexone versus placebo on drinks per drinking day (DPDD; p = 0.03), percent heavy drinking days ( p = 0.004), and daily drinking ( p = 0.02). As compared to placebo, individuals in the high reward/low relief phenotype who received daily naltrexone had significantly fewer DPDD (Cohen's d = 2.05) and had a lower proportion of heavy drinking days (Cohen's d = 1.75). As hypothesized, reductions in average desire to drink mediated the effect of naltrexone on average daily drinking among the high reward/low relief drinkers (moderated mediation effect: p = 0.029). Conclusions This theory‐driven study replicates the empirical finding that naltrexone is particularly efficacious among high reward/low relief drinkers. Our study brings the field a step closer to the potential of using a precision medicine approach to treating alcohol use disorder.