Topiramate for cocaine dependence during methadone maintenance treatment: a randomized controlled trial

Abstract

Background: Dual dependence on opiate and cocaine occurs in about 60% of patients admitted to methadone maintenance and negatively impacts prognosis (Kosten et al. 2003. Drug Alcohol Depend. 70, 315). Topiramate (TOP) is an antiepileptic drug that may have utility in the treatment of cocaine dependence because it enhances the GABAergic system, antagonizes the glutamatergic system, and has been identified by NIDA as one of only a few medications providing a "positive signal" warranting further clinical investigation. (Vocci and Ling, 2005. Pharmacol. Ther. 108, 94).

Method: In this double-blind controlled clinical trial, cocaine dependent methadone maintenance patients (N=171) were randomly assigned to one of four groups. Under a factorial design, participants received either TOP or placebo, and monetary voucher incentives that were either contingent (CM) or non-contingent (Non-CM) on drug abstinence. TOP participants were inducted onto TOP over 7 weeks, stabilized for 8 weeks at 300 mg daily then tapered over 3 weeks. Voucher incentives were supplied for 12 weeks, starting during the fourth week of TOP induction. Primary outcome measures were cocaine abstinence (Y/N) as measured by thrice weekly urinalysis and analyzed using Generalized Estimating Equations (GEE) and treatment retention. All analyses were intent to treat and included the 12-week evaluation phase of combined TOP/P treatment and voucher intervention period.

Results: There was no significant difference in cocaine abstinence between the TOP vs. P conditions nor between the CM vs. Non-CM conditions. There was no significant TOP/CM interaction. Retention was not significantly different between the groups.

Conclusion: Topiramate is not efficacious for increasing cocaine abstinence in methadone patients.

Trial registration: ClinicalTrials.gov NCT00685178.

Keywords: Antiepileptic; Cocaine dependence; Contingency Management; GABA; Glutamate; Topiramate.

Conflict of interest statement

No authors have any financial or other conflict of interest.

Copyright © 2014. Published by Elsevier Ireland Ltd.

Figures

Figure 1

Study Timeline

Figure 2

Consort Diagram

Figure 3

Retention during the combined treatment evaluation phase

Figure 4

Upper panel: Percent cocaine negative urine samples per participant by treatment groups (modified Preston rule). Dots represent the percentage of cocaine negative urine samples for individual participants. The bars represent the mean proportion of cocaine negative urine samples for the group. Lower panel: Longest duration of cocaine abstinence by treatment groups as shown by the number of consecutive cocaine negative urine samples

Figure 5

Combination of self-reported abstinence, biochemical confirmation of abstinence, and no missing samples across the 12-week combined treatment evaluation phase