Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial.

IMPORTANCE: It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy. OBJECTIVE: To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention. INTERVENTIONS: Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76. MAIN OUTCOMES AND MEASURES: Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior. RESULTS: Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95% CI, 2.2-19.2; P < .001). From weeks 12 through 64, 45% (18 of 40) among those in the varenicline group vs 15% (7 of 47) in the placebo group were continuously abstinent (OR, 4.6; 95% CI, 1.5-15.7; P = .004), and from weeks 12 through 76, 30% (12 of 40) in the varenicline group vs 11% (5 of 47) in the placebo group were continuously abstinent (OR, 3.4; 95% CI, 1.02-13.6; P = .03). There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events. CONCLUSIONS AND RELEVANCE: Among smokers with serious mental illness who attained initial abstinence with standard treatment, maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00621777.

Varenicline for Smoking Cessation in Schizophrenia: Safety and Effectiveness in a 12-Week, Open-Label Trial.

OBJECTIVES: Varenicline was approved by the FDA in 2006. In 2009, based largely on case reports, the FDA issued a warning of possible adverse neuropsychiatric effects including depression and suicidal thoughts and behavior for varenicline and bupropion. Prospective trials of varenicline have not reported increased incidence of psychiatric adverse events other than sleep disturbance, but smokers with major mental illness have been excluded from large prospective trials of varenicline to date. We sought to evaluate the effect of a standard open-label 12-week varenicline trial on prospectively assessed safety and smoking outcomes in stable, treated adults with schizophrenia spectrum disorder and nicotine dependence. METHODS: One-hundred-and-twelve stable outpatients who smoked >10 cigarettes/day participated in a 12-week, open-label, smoking cessation trial of varenicline and weekly group cognitive behavioral therapy. Participants took varenicline for 4 weeks before attempting cessation. Trained raters collected safety and smoking outcome data weekly. RESULTS: Participants demonstrated improved psychotic symptoms, depressive symptoms and nicotine withdrawal symptoms from baseline to week 12 or early termination. At the end of 12 weeks open label treatment, the 14- and 28-day continuous abstinence rates were 47.3 and 34%, respectively. Expired CO declined significantly during treatment in those who did not achieve abstinence. CONCLUSIONS: This prospective study suggests that varenicline may be well-tolerated and effective for smoking cessation in combination with group CBT in stable outpatients with schizophrenia, a group with high rates of smoking and smoking-attributable morbidity and mortality.