title: A Randomized Trial Evaluating Whether Topiramate Aids Smoking Cessation and Prevents Alcohol Relapse in Recovering Alcohol-Dependent Men.
abstract: Alcohol and nicotine dependence frequently co-occur, and quitting smoking might enhance long-term alcohol abstinence. Topiramate appears to help non-alcohol-dependent individuals quit smoking, and our pilot work suggested efficacy only in men. It also prevents relapse to alcohol in recently detoxified alcoholics. We evaluated topiramate in abstinent alcohol-dependent men to assess whether this medication (i) promotes smoking cessation and (ii) prevents alcohol and other drug relapse in the context of smoking cessation treatment.
  
  
  
  One hundred and twenty-nine alcohol-abstinent (mean ~6 months) alcohol-dependent male smokers (80% with other substance use disorders) participated in this 12-week randomized, double blind, parallel group comparison of topiramate (up to 200 mg/d) and placebo with a 24-week nontreatment follow-up period. The study was carried out sequentially at 2 academic centers in the Midwest and Southern California between March 23, 2009 and November 20, 2014. All participants received manual-guided smoking cessation counseling combined with medication-focused compliance enhancement therapy. Randomization was block designed by the research pharmacist in a 1:1 ratio. Participants, investigators, and research personnel were masked to treatment assignment. The primary smoking end point was biochemically confirmed 4-week continuous abstinence from smoking during weeks 9 to 12, while the secondary end point was relapse to any drinking or drug use during the entire 36-week evaluation period. Logistic regression was used to determine the effects of topiramate on quitting smoking and alcohol relapse, controlling for relevant covariates. The trial is registered at ClinicalTrials.gov (number NCT00802412) and is now closed.
  
  
  
  Only a small proportion (7.9%) of topiramate-treated participants were able to quit smoking, and this cessation rate was similar to placebo (10.6%; odds ratio = 1.60; 95% confidence interval 0.4, 6.5; p = 0.51). Roughly 30% of the sample had a documented relapse to drinking or drug use during the study, and these rates were similar in the topiramate (20/63; 31.8%) and placebo groups (18/66; 27.3%; p = 0.58). Results of a longitudinal logistic regression model examining time to any alcohol relapse revealed no medication effect.
  
  
  
  Topiramate at a daily dosage of up to 200 mg per day, combined with smoking cessation and medication adherence counseling, had no effects on smoking cessation or the prevention of alcohol or drug relapse in male smokers who were in early or sustained full remission from alcohol and motivated to make a quit attempt. Alternative approaches for treating this high-risk, dually dependent population are needed.
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.|Department of Psychiatry, Health Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Anthenelli
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jaimee L
authors.initials: JL
authors.lastname: Heffner
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.|Department of Psychiatry, Health Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Esther
authors.initials: E
authors.lastname: Wong
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.
authors.forename: Jessie
authors.initials: J
authors.lastname: Tibbs
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.
authors.forename: Katie
authors.initials: K
authors.lastname: Russell
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.|Department of Psychiatry, Health Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Melodie
authors.initials: M
authors.lastname: Isgro
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dinh
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.
authors.forename: Chris
authors.initials: C
authors.lastname: Wehrle
authors.affiliation: Pacific Treatment and Research Center, VA San Diego Healthcare System, San Diego, California.|Department of Psychiatry, Health Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Matthew J
authors.identifier: 0000-0003-2768-1099
authors.initials: MJ
authors.lastname: Worley
authors.affiliation: Department of Psychiatry, Health Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Neal
authors.initials: N
authors.lastname: Doran
mesh_terms: D000328:Adult; D064829:Alcohol Abstinence; D000437:Alcoholism / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012907:Smoking / Q000188:drug therapy* / Q000453:epidemiology; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000453:epidemiology; D000077236:Topiramate
chemical_list: D000077236:Topiramate; D005632:Fructose
keywords: Alcohol; Nicotine; Relapse Prevention; Smoking Cessation; Topiramate