Comparing and Combining Topiramate and Aripiprazole on Alcohol-Related Outcomes in a Human Laboratory Study

Abstract

Aims: The goal of this study was to evaluate the efficacy of topiramate up to 200 mg/day and of aripiprazole up to 15 mg/day, alone and combined, in reducing alcohol-related outcomes in a human laboratory study.

Method: This was a 5 week, between-subject, double-blind, placebo-controlled human laboratory study with topiramate [0 mg/day (placebo), 100 mg/day, 200 mg/day] and aripiprazole [0 mg/day (placebo), 7.5 mg/day, 15 mg/day] in 90 non-treatment seeking, heavy drinking, alcohol-dependent individuals. Main outcomes were the efficacy of 200 mg/day topiramate and 15 mg/day aripiprazole, alone and combined, in reducing drinks consumed during an alcohol self-administration procedure (human laboratory phase) and while receiving the study medications prior to the laboratory session (naturalistic drinking phase). Other outcomes in the laboratory phase included alcohol craving, and alcohol biphasic effects.

Results: In the human laboratory phase, topiramate 200 mg/day reduced alcohol craving [**P < 0.01] and amplified alcohol-induced stimulation [*P < 0.05], but did not reduce the number of drinks consumed. Topiramate 200 mg/day was also effective in reducing drinking days [*P < 0.05], and alcohol craving [*P < 0.05], in the naturalistic drinking phase. No significant findings were found for aripiprazole for any of the outcomes analyzed.

Conclusion: Participants receiving 200 mg/day topiramate reported reduced alcohol drinking and craving, and increased alcohol-related stimulation. These findings provide further support for the role of topiramate as a pharmacological treatment for AUD.

Clinicaltrial.gov identifier: NCT00884884.

Short summary: This study tested topiramate and aripiprazole alone and in combination. The results replicate past findings and suggest that topiramate may be an effective treatment for alcohol use disorder. The present results suggest that the combination of topiramate and aripiprazole do not warrant further evaluation.

Figures

Fig. 1.

Study design. The study included a telephone pre-screening, in-person screening, naturalistic phase (5-week outpatient dosing of the study medications), human laboratory phase (ASA experimental session), 1-week medications down titration and finally 1-month follow-up.

Fig. 2.

CONSORT diagram showing the flow of participants through each phase of the study.

Fig. 3.

Topiramate 200 mg/day effect for drinking days (DD), alcohol craving during the naturalistic drinking phase and effects on alcohol craving and on BAES in the laboratory. In the naturalistic phase, (A) there was a significant main effect for 200 mg/day topiramate [F(1,29) = 9.44, *P = 0.042, f = 0.26]. In the laboratory before alcohol prime, (B) there was a 200 mg/day topiramate main effect on AUQ [F(1,35) = 5.21, *P = 0.029, f = 0.27], there was also a 200 mg/day topiramate × time interaction [F(1,33) = 6.93, *P = 0.013, f = 0.31]. In the laboratory after alcohol prime, there was a significant 200 mg/day topiramate × time interaction [F(1,35) = 4.51, *P = 0.041, f = 0.25]. Post hoc testing indicated no difference between the two groups on the descending limb [t(34) = 1.47, P > 0.05]. (D) There was no 15 mg/day aripiprazole × time for subscale stimulation score and no significant differences between groups in the subscale sedation score [P’s ns]. Results are reported as M and error bars indicate SEM; not significant [P > 0.05].