title: Zonisamide Reduces Withdrawal Symptoms But Does Not Enhance Varenicline-Induced Smoking Cessation.
abstract: BACKGROUND
  Varenicline (Chantix) is a first-line treatment for smoking cessation but does not produce cessation in many individuals. It may be possible to improve abstinence by co-administering varenicline with other medications. Zonisamide (Zonegran) has a similar pharmacologic profile to topiramate, which has been shown to reduce smoking, but is better tolerated. This study evaluated whether combined zonisamide and varenicline reduced tobacco withdrawal and increased abstinence among smokers trying to quit, relative to varenicline and placebo.
  
  
  METHODS
  This was a double-blind, randomized, placebo-controlled pilot trial of zonisamide + varenicline versus placebo + varenicline for smoking cessation. Smokers received brief counseling and study medications, and completed weekly assessments for 10 consecutive weeks. The primary outcome was continuous abstinence rates (biochemically verified) during the final 4 weeks of treatment.
  
  
  RESULTS
  Results are presented as intent-to-treat and completer analyses. Seventy-four individuals were enrolled; 45 completed the study. Overall, 14.9% (intent-to-treat) and 25.0% (completer) of participants maintained sustained abstinence during the final 4 weeks of treatment. There were no differences between groups for biochemically-verified smoking, but zonisamide + varenicline reduced self-reported smoking, nicotine withdrawal, and craving compared to placebo + varenicline.
  
  
  CONCLUSIONS
  Zonisamide decreased nicotine withdrawal and craving, though not of sufficient magnitude to modify smoking behavior. The sample size was small and low rates of abstinence across groups suggest the study population was difficult to treat. Additional evaluation of zonisamide or other medications that increase GABA or decrease glutamate in larger or more diverse populations may yield positive clinical benefit for nicotine/tobacco cessation.
  
  
  CONCLUSIONS
  This study provides support for layering novel medications with varenicline for smoking cessation, for investigating medications that target the GABA and glutamate system, and for assessing the contribution that reductions in nicotine withdrawal have on ultimate cessation outcomes.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD;
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Dunn
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD;
authors.forename: Taylor F
authors.initials: TF
authors.lastname: Marcus
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD;
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kim
authors.affiliation: Schroeder Statistical Consulting, Ellicott City, MD.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Schroeder
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD;
authors.forename: Ryan
authors.initials: R
authors.lastname: Vandrey
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; annieumbricht@jhu.edu.
authors.forename: Annie
authors.initials: A
authors.lastname: Umbricht
mesh_terms: D000328:Adult; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods* / Q000706:statistics & numerical data*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D000068580:Varenicline / Q000627:therapeutic use*; D000078305:Zonisamide
chemical_list: D007555:Isoxazoles; D018722:Nicotinic Agonists; D000078305:Zonisamide; D000068580:Varenicline