Effects of varenicline on cognitive performance in heavy drinkers: Dose-response effects and associations with drinking outcomes

Abstract

Varenicline reduces drinking in people with alcohol use disorder, but little is known about the mechanisms underlying this effect. Varenicline targets α4β2 and α7 nicotinic acetylcholine receptors, which are associated with several cognitive functions such as working memory. Varenicline may improve drinking outcomes by enhancing cognitive functioning. The current manuscript reports on cognitive outcomes from a placebo-controlled, double-blind human laboratory experiment examining the effects of varenicline on drinking behavior (Verplaetse et al., 2016a). Participants were 55 adult heavy drinkers who met criteria for an alcohol use disorder. They were randomized to receive varenicline (1 mg/day, 2 mg/day) or placebo. They completed a baseline assessment of cognitive functioning (i.e., digits backward task, continuous performance task) before starting medication. After a medication titration period, they attended a laboratory session (post medication Day 8) where they completed the cognitive assessment battery and an alcohol-primed ad libitum drinking task. Blood was collected to measure plasma varenicline levels. Varenicline produced dose-dependent improvements in working memory. Although there was no significant effect of oral varenicline dose on response time on the continuous performance task, participants with higher levels of plasma varenicline showed greater improvement of reaction time (RT). Among participants receiving 2 mg/day varenicline, larger improvements in working memory were associated less drinking, although mediation analyses did not find a significant indirect effect. These findings suggest that varenicline can improve working memory above baseline levels in heavy drinkers. Varenicline may reduce rates of alcohol use by improving working memory. (PsycINFO Database Record

Trial registration: ClinicalTrials.gov NCT00580645.

(c) 2018 APA, all rights reserved).

Figures

Figure 1

Effects of varenicline on digit backwards score. Capped bars indicated standard error. Starred bracket indicates significant difference between baseline and active medication, *p = 0.001. dz is the effect size.

Figure 2

Effects of varenicline on reaction time during target trials on the continuous performance task. Capped bars indicate standard error. Bracket with t indicates that medication effect approached significance, p = 0.081. dz is effect size.

Figure 3

Association between medication-induced improvements on digit backwards task and number of drinks consumed during the ad libitum consumption task. Solid line shows the least squares regression line of best fit with coefficient of determination. The associations in the placebo and 1 mg/day conditions were not significant and are not shown.