title: Fine-grain analysis of the treatment effect of topiramate on methamphetamine addiction with latent variable analysis.
abstract: 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.
authors.affiliation: Department of Public Health Sciences, University of Virginia, PO Box 800717, Charlottesville, VA 22908, USA. jzm4h@virginia.edu
authors.forename: Jennie Z
authors.initials: JZ
authors.lastname: Ma
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Elmer
authors.initials: E
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Weiss
authors.forename: Frances
authors.initials: F
authors.lastname: McSherry
authors.forename: Jim
authors.initials: J
authors.lastname: Saadvandi
authors.forename: Erin
authors.initials: E
authors.lastname: Iturriaga
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rawson
authors.forename: Mark
authors.initials: M
authors.lastname: Hrymoc
authors.forename: Jan
authors.initials: J
authors.lastname: Campbell
authors.forename: Charles
authors.initials: C
authors.lastname: Gorodetzky
authors.forename: William
authors.initials: W
authors.lastname: Haning
authors.forename: Barry
authors.initials: B
authors.lastname: Carlton
authors.forename: Joseph
authors.initials: J
authors.lastname: Mawhinney
authors.forename: Dennis
authors.initials: D
authors.lastname: Weis
authors.forename: Michael
authors.initials: M
authors.lastname: McCann
authors.forename: Tony
authors.initials: T
authors.lastname: Pham
authors.forename: Christopher
authors.initials: C
authors.lastname: Stock
authors.forename: Ruth
authors.initials: R
authors.lastname: Dickinson
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elkashef
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D016739:Behavior, Addictive / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects; D008875:Middle Aged; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000077236:Topiramate; D005632:Fructose; D008694:Methamphetamine