Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial Ahmed Elkashef 1 , Roberta Kahn 1 , Elmer Yu 2 , Erin Iturriaga 1 , Shou-Hua Li 1 , Ann Anderson 1 , Nora Chiang 1 , Nassima Ait-Daoud 3 , David Weiss 4 , Frances McSherry 4 , Tracey Serpi 4 , Richard Rawson 5 , Mark Hrymoc 5 , Dennis Weis 6 , Michael McCann 7 , Tony Pham 7 , Christopher Stock 8 , Ruth Dickinson 8 , Jan Campbell 9 , Charles Gorodetzky 9 , William Haning 10 , Barry Carlton 10 , Joseph Mawhinney 11 , Ming D. Li 3 & Bankole A. Johnson 3 National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA, 1 Veterans Administration Medical Center, Philadelphia, PA, USA, 2 Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA, 3 Department of Veterans Affairs Cooperative Studies Program Coordinating Center, Perry Point, MD, USA, 4 UCLA Integrated Substance Abuse Programs, Los Angeles, CA, USA, 5 Lutheran Hospital Office of Research, Des Moines, IA, USA, 6 Matrix Institute on Addictions, Costa Mesa, CA, USA, 7 Department of Veterans Affairs, Salt Lake City Health Care System, Salt Lake City, UT, USA, 8 Department of Psychiatry, University of Missouri, Kansas City, MO, USA, 9 Pacific Addiction Research Center, Honolulu, HI, USA 10 and South BayTreatment Center, San Diego, CA, USA 11 ABSTRACT Aims Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled out-patient trial tested topiramate for treating methamphetamine addiction. Design Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 50 mg/day to the target maintenance of 200 mg/day in weeks 6–12 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. Setting The trial was conducted at eight medical centers in the United States. Participants One hundred and forty methamphetamine-dependent adults took part in the trial. Measurements The primary outcome was abstinence from methamphetamine during weeks 6–12. Secondary out- comes included use reduction versus baseline, as well as psychosocial variables. Findings In the intent-to-treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 6–12. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer-rated severity of dependence scores significantly. Subjects with negative urine before randomization (n = 26) had significantly greater abstinence on topi- ramate versus placebo during study weeks 6–12. Topiramate was safe and well tolerated. Conclusions Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent. Keywords Abstinence facilitation, methamphetamine abuse, topiramate, treatment. Correspondence to: Bankole A. Johnson, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, PO Box 800623, Charlottesville, VA 22908-0623, USA. E-mail: bankolejohnson@virginia.edu Submitted 21 October 2010; initial review completed 30 December 2010; final version accepted 9 December 2011 INTRODUCTION After a positive finding in a proof-of-concept study of topiramate in alcoholics [1] and a successful multi-site, placebo-controlled, randomized trial of topiramate for alcohol dependence [2], topiramate was considered an appropriate candidate for treating stimulant abuse. In a placebo-controlled pilot study, topiramate was effective at reducing cocaine use after the full dose of topiramate was achieved in week 8 [3]. Two potential mechanisms of action are relevant to the treatment of stimulant abuse. Topiramate facilitates gamma-aminobutyric acid (GABA)ergic function through a non-benzodiazepine site on the GABA-A (GABAA) receptor, depressing cortico-mesolimbic dopam- inergic activity. Pharmacologically increasing GABA RESEARCH REPORT doi:10.1111/j.1360-0443.2011.03771.x © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction Addiction