A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder

J Clin Psychiatry. 2012 May;73(5):654-60. doi: 10.4088/JCP.11m07522.


Objective: Effective smoking cessation treatments are needed for patients with schizophrenia, who, compared with the general population, have high rates of cigarette smoking and more difficulty quitting. We evaluated the safety and efficacy of varenicline for smoking cessation in outpatients with stable schizophrenia or schizoaffective disorder.

Method: In this 12-week, randomized, double-blind, multicenter trial (May 8, 2008, to April 1, 2010), 127 smokers (≥ 15 cigarettes/d) with DSM-IV-confirmed schizophrenia or schizoaffective disorder received varenicline or placebo (2:1 ratio). The primary outcome was safety and tolerability of varenicline assessed by adverse events frequency and changes in ratings on the Positive and Negative Syndrome Scale and other psychiatric scales from baseline to 24 weeks. Abstinence was defined as no smoking 7 days prior to weeks 12 and 24, verified by carbon monoxide level.

Results: Eighty-four participants received varenicline; 43, placebo. At 12 weeks (end of treatment), 16/84 varenicline-treated patients (19.0%) met smoking cessation criteria versus 2/43 (4.7%) for placebo (P = .046). At 24 weeks, 10/84 (11.9%) varenicline-treated and 1/43 (2.3%) placebo-treated patients, respectively, met abstinence criteria (P = .090). Total adverse event rates were similar between groups, with no significant changes in symptoms of schizophrenia or in mood and anxiety ratings. Rates of suicidal ideation adverse events were 6.0% (varenicline) and 7.0% (placebo) (P = 1.0). There was 1 suicide attempt by a varenicline patient with a lifetime history of similar attempts and no completed suicides.

Conclusions: Varenicline was well tolerated, with no evidence of exacerbation of symptoms, and was associated with significantly higher smoking cessation rates versus placebo at 12 weeks. Our findings suggest varenicline is a suitable smoking cessation therapy for patients with schizophrenia or schizoaffective disorder.

Trial registration: ClinicalTrials.gov identifier: NCT00644969.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Canada
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / therapeutic use*
  • Psychotic Disorders / rehabilitation*
  • Quinoxalines / adverse effects
  • Quinoxalines / therapeutic use*
  • Schizophrenia / rehabilitation*
  • Smoking Cessation*
  • United States
  • Varenicline


  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Varenicline

Associated data

  • ClinicalTrials.gov/NCT00644969