Fine-grain analysis of the treatment effect of topiramate on methamphetamine addiction with latent variable analysis

Background: As reported previously, 140 methamphetamine-dependent participants at eight medical centers in the U.S. were assigned randomly to receive topiramate (N=69) or placebo (N=71) in a 13-week clinical trial. The study found that topiramate did not appear to reduce methamphetamine use significantly for the primary outcome (i.e., weekly abstinence from methamphetamine in weeks 6-12). Given that the treatment responses varied considerably among subjects, the objective of this study was to identify the heterogeneous treatment effect of topiramate and determine whether topiramate could reduce methamphetamine use effectively in a subgroup of subjects. Methods: Latent variable analysis was used for the primary and secondary outcomes during weeks 6-12 and 1-12, adjusting for age, sex, and ethnicity. Results: Our analysis of the primary outcome identified 30 subjects as responders, who either reduced methamphetamine use consistently over time or achieved abstinence. Moreover, topiramate recipients had a significantly steeper slope in methamphetamine reduction and accelerated to abstinence faster than placebo recipients. For the secondary outcomes in weeks 6-12, we identified 40 subjects as responders (who had significant reductions in methamphetamine use) and 65 as non-responders; topiramate recipients were more than twice as likely as placebo recipients to be responders (odds ratio = 2.67; p = 0.019). Separate analyses of the outcomes during weeks 1-12 yielded similar results. Conclusions: Methamphetamine users appear to respond to topiramate treatment differentially. Our findings show an effect of topiramate on the increasing trend of abstinence from methamphetamine, suggesting that a tailored intervention strategy is needed for treating methamphetamine addiction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.