Aripiprazole Suppression of Drinking in a Clinical Laboratory Paradigm: Influence of Impulsivity and Self-Control

Abstract

Background: Aspects of impulsivity have been implicated in the development, or maintenance, of alcohol use disorder (AUD). The brain dopamine system is implicated in both reward processing/memory (typically subcortical) and in brain inhibitory control mechanisms (typically cortical). Using a validated clinical laboratory paradigm, the dopamine/serotonin "stabilizing" drug, aripiprazole was evaluated in non-treatment-seeking AUD individuals based on their level of impulsivity/self-control.

Methods: Ninety-nine individuals (77% male; mean age 27; 7.5 drinks per day; 83% heavy drinking days) meeting DSM-IV criteria for alcohol dependence were randomized to aripiprazole (N = 47 evaluable) or placebo (N = 48 evaluable) based on their Barratt Impulsiveness Scale (BIS-11) score (above or below 68). Aripiprazole, or similar placebo, was titrated to 15 mg over 8 days. Drinking was recorded over 6 days under natural conditions. On Day 8, after 1 day of required abstinence, individuals participated in a bar laboratory paradigm that included a priming drink (breath alcohol concentration [BAC] target 0.02 to 0.03 g/dl) and free-choice consumption of up to 8 drinks (max BAC 0.1 g/dl) in exchange for a "bar credit" of $2 per drink (max $16). End points were drinks per day under natural conditions and drinks consumed in the bar laboratory after the priming drink.

Results: There was no significant main effect of aripiprazole or interaction with BIS-11 score during the natural drinking period. However, there was a main effect of aripiprazole on bar laboratory drinking (p = 0.04) and aripiprazole reduced the total number of drinks consumed more among individuals with low self-control (p = 0.034) and increased latency to consume those drinks (p = 0.045) more among those with high impulsivity. Relative to placebo, aripiprazole caused more side effects and increased alcohol-induced sedation, but neither significantly influenced its interaction with impulsivity/self-control scores on drinking.

Conclusions: This paradigm forced a choice between immediate drinking reward and delayed monetary reward. In those with high impulsivity and/or low self-control, aripiprazole shifts the balance away from immediate drinking toward a later reward. Medications targeting cortical dopamine/serotonin balance might show clinical benefit of reduced drinking, among individuals with impulsivity/low self-control.

Keywords: Alcohol; Alcohol Use Disorder; Aripiprazole; Impulsivity; Pharmacotherapy.

Figure 1

Drinks per day (mean +/− SEM) during the 6-day natural observation period in those with low or high impulsivity (BIS-11) scores while taking placebo or aripiprazole. See text for statistical analysis. Figures are adjusted for baseline drinks per day.

Figure 2

Free choice drinks (mean +/− SEM) consumed in the bar lab after a priming drink in those with low or high impulsivity (BIS-11) scores while taking placebo or aripiprazole. See text for statistical analysis. Figures are adjusted for baseline drinks per drinking day.

Figure 3

Free choice drinks (mean +/− SEM) consumed in the bar lab after a priming drink in those with low or high self-control scores (BIS-11 subscale) while taking placebo or aripiprazole. See text for complete statistical analysis. * significant interaction of self-control level and medication (p < 0.05), ** significant difference in medication effect in low self-control group (p = 0.01). Figures are adjusted for baseline drinks per drinking day.

Figure 4

Mean time to first sip (min) of successive drinks from the first tray of free-choice drinks as a function of BIS-11 scores and medication. Brackets indicate the number of participants in each group who drank that number of drinks. The interaction between BIS-11 group and medication on latencies between drinks was significant (p < 0.05), such that aripiprazole, relative to placebo. increased latencies between drinks among high BIS, but not low BIS, subjects.