Effect of Lowering the Dose of Varenicline on Alcohol Self-administration in Drinkers With Alcohol Use Disorders

Abstract

Objectives Varenicline (2mg/day) has been shown to be efficacious in reducing alcohol consumption. A lower dose of varenicline may be effective in reducing alcohol use while minimizing the potential for side effects. Methods This double-blind, placebo-controlled investigation examined the effect of varenicline (0, 1, 2 mg/day) on alcohol consumption in non-treatment seeking adults meeting DSM-IV criteria for alcohol use disorders (n = 60). Following 7-days of medication pretreatment, participants were administered a low fixed dose of alcohol (0.3 g/dL), and subjective and physiologic responses were assessed. A 2-hour ad-libitum alcohol self-administration period followed. We also explored relationships between plasma varenicline levels and consumption. Results Overall, frequency and severity of adverse events were minimal. The 1mg/day dose reduced the frequency of insomnia compared to the 2mg/day dose. The 2 mg/day varenicline dose versus placebo reduced alcohol craving and showed limited effect on reduced alcohol consumption. Alcohol craving and consumption did not differ between the 1 mg/day varenicline dose versus placebo. Trough varenicline plasma levels ≥ 3 ng/ml were associated with reduced drinking and levels ≥ 5ng/ml were associated with reduced heavy drinking. Conclusions Overall, we found no evidence supporting an effect of 1 mg/day varenicline on craving or consumption, suggesting that doses of varenicline less than 2mg/day may not be effective in reducing alcohol-related outcomes. Importantly, results suggest that higher plasma levels of varenicline may be needed in order to maximize the effect of varenicline on alcohol consumption and should be investigated in drinkers meeting criteria for alcohol use disorders.

Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings

“…Of the n=60 subjects who completed the parent study, n=44 elected to also complete the current protocol. Briefly, in the parent study, varenicline was titrated to steady-state levels over 7 days, and participants then completed a single laboratory session examining alcohol self-administration (Verplaetse et al, in press ). Following the self-administration session, participants who enrolled in the present investigation were maintained at steady-state varenicline levels for an additional three week period.…”

“…This effect was observed in a more recent study on alcohol-primed behaviors such that 0.3 mg/kg varenicline gave rise to a non-significant increase on alcohol responding (Randall et al, 2015). We have recently completed the first study on the effects of lowering the dose of varenicline on alcohol self-administration in individuals with AUDs (Verplaetse et al, in press ), the parent study to the present investigation. We found a modest effect of varenicline (2 mg/day) on reduced alcohol consumption and craving, but no dose-ranging effect of varenicline at the doses tested (1 and 2 mg/day)(Verplaetse et al, in press ).…”

Effects of varenicline on alcohol self-administration and craving in drinkers with depressive symptoms

“…Moreover, VAR plasma level was a stronger predictor of craving and ad libitum drinking than was oral VAR dose, suggesting that VAR plasma may provide a better estimate of treatment efficacy than would analyzing outcomes according to dosing condition. The current reanalysis will build on our previous findings (Verplaetse et al, 2016) demonstrating that VAR plasma levels show a negative relationship with craving and ad libitum drinking, such that individuals with higher levels of VAR plasma report less alcohol craving and consume less alcohol. We predicted that this effect would be moderated by participants’ self-reported depressive symptoms, such that participants reporting more depressive symptoms would show a greater reduction in drinking when VAR plasma levels were high.…”

“…Our group (Verplaetse et al, 2016) recently completed a human laboratory study testing the efficacy of VAR in a group of adult drinkers meeting criteria for alcohol use disorders. We found evidence that VAR effectively reduced drinking risk in this cohort, as indicated by reductions in alcohol craving and ad libitum alcohol consumption during a laboratory drinking task.…”

“…Little is known, however, about treatment moderators that may influence efficacy. The current study reanalyzed data from a human laboratory study (Verplaetse et al, 2016) to determine whether VAR was more effective at reducing alcohol use among drinkers reporting symptoms of depression. Participants were 60 adults meeting DSM-IV criteria for alcohol use disorders ( n = 60) who were randomly assigned to receive VAR (1 mg/day, 2 mg/day) or placebo.…”