Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence - PubMed (original) (raw)

Randomized Controlled Trial

. 2018 Apr;42(4):751-760.

doi: 10.1111/acer.13601. Epub 2018 Feb 12.

Affiliations

Randomized Controlled Trial

Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence

Raymond F Anton et al. Alcohol Clin Exp Res. 2018 Apr.

Abstract

Background: The opioid antagonist naltrexone is not efficacious for every alcohol treatment seeker. However, various individual factors, such as genetic differences and nicotine-use/smoking status, have been suggested as predictors of naltrexone response. In a randomized clinical trial, we previously reported that nicotine-use/smoking status might be a stronger predictor of naltrexone efficacy than OPRM1 A118G single nucleotide polymorphism (SNP) genotype. In this report, we further characterize the nicotine-users in that trial, examine other drinking outcomes, examine the influence of smoking change on naltrexone effects on drinking, and validate the result in smokers with disialo carbohydrate-deficient transferrin (%dCDT) change as an independent biomarker of response.

Methods: Individuals (n = 146) meeting DSM-IV criteria for alcohol dependence who were genotyped for the OPRM1 A118G SNP and who did, or did not, use nicotine/cigarettes were randomized, in a balanced fashion, to naltrexone (50 mg/d) or placebo and provided medical management (MM) over a 16-week clinical trial. Alcohol use and smoking during the trial were assessed and analyzed.

Results: Nicotine-use/smoking status significantly interacted with medication in reducing percent heavy drinking days (PHDD) during the trial (p = 0.003), such that nicotine-users/smokers showed significantly lower PHDD on naltrexone versus placebo (p = 0.0001, Cohen's d = 0.89), while nonusers showed no significant difference between naltrexone and placebo (p = 0.95, Cohen's d = 0.02). Similar effects were shown for drinks per day and percent days drinking. The superiority of naltrexone over placebo on PHDD reduction in nicotine-users/smokers was confirmed with %dCDT (Cohen's d range 0.3 to 0.9 over the study). Naltrexone did not significantly change cigarette use in smokers, and change in use did not influence naltrexone's effect on PHDD.

Conclusions: These data confirm past findings that naltrexone is more efficacious in those who use nicotine/cigarettes. Compared to previous work on the OPRM1 A118G SNP, it appears that nicotine-use might be a more salient predictor of naltrexone treatment response. While naltrexone did not change cigarette use during the study, and smoking change was not related to alcohol reduction, it should be noted that participants were not seeking smoking cessation and MM did not address this issue.

Keywords: Alcohol; Alcohol Use Disorder; Naltrexone; Nicotine-Use; Treatment.

Copyright © 2018 by the Research Society on Alcoholism.

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Conflict of interest statement

All other authors report no biomedical conflicts of interest.

Figures

Figure 1

Figure 1

Consort diagram of study design and recruitment and randomization.

Figure 2

Figure 2

Percent heavy drinking days (means +/− SEM) during the study in non-nicotine and nicotine users treated with naltrexone or placebo. * significant interaction of nicotine-use by medication group (p = 0.003). ** significant difference in naltrexone vs. placebo in nicotine users (p = 0.0001).

Figure 3

Figure 3

Drinks per day (means +/− SEM) during the study in non-nicotine and nicotine users treated with naltrexone or placebo. * significant interaction of nicotine-use by medication group (p = 0.008). ** significant difference in naltrexone vs. placebo in nicotine users (p = 0.0001).

Figure 4

Figure 4

Percent drinking days (means +/− SEM) during the study in non-nicotine and nicotine users treated with naltrexone or placebo. * significant interaction of nicotine-use by medication group (p = 0.015). ** significant difference in naltrexone vs. placebo in nicotine users (p = 0.016).

Figure 5

Figure 5

A) Percent heavy drinking days (means +/− SEM) over the course of the study in nicotine users treated with naltrexone or placebo. B) Parallel change in %dCDT, a blood marker of heavy drinking, in the same individuals over the course of the study. Effect sizes (Cohen’s d) and significance is provided for the naltrexone vs. placebo contrast at various study weeks for both verbally reported heavy drinking days and %dCDT blood marker of heavy drinking days.

Figure 6

Figure 6

Means (SEM) of percent heavy drinking days (left axis and stippled color) and cigarettes per smoking day (right axis and solid color) in 52 smokers over the course of the study in those treated with naltrexone or placebo. Naltrexone treatment led to significantly less PHDD than placebo at both week 8 (p=0.02) and week 16 (p=0.02) of treatment. There was no significant difference between naltrexone or placebo in cigarette use at either week 8 or week 16.

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