Varenicline for smoking cessation in bipolar disorder: a randomized, double-blind, placebo-controlled study.

Objective: Virtually no clinical trials for smoking cessation have been undertaken in bipolar disorder. Varenicline has shown efficacy for smoking cessation, but warnings about neuropsychiatric adverse events have been issued. We assessed the efficacy and safety of varenicline in euthymic bipolar subjects motivated to quit smoking.

Method: Clinically stable adult patients with DSM-IV bipolar disorder (n = 60) who smoked ≥ 10 cigarettes per day were randomized to a 3-month, double-blind, placebo-controlled varenicline trial and a 3-month follow-up. Study enrollment was completed from February 2010 through March 2013. Varenicline was dosed using standard titration, and smoking cessation counseling was provided to all patients. The primary outcome was defined as a 7-day point prevalence of self-reported no smoking verified by expired carbon monoxide level < 10 ppm at 12 weeks. Psychopathology and side-effects were assessed at each visit.

Results: At 3 months (end of treatment), significantly more subjects quit smoking with varenicline (n/n = 15/31, 48.4%) than with placebo (n/n = 3/29, 10.3%) (OR = 8.1; 95% CI, 2.03-32.5; P < .002). At 6 months, 6 of 31 varenicline-treated subjects (19.4%) remained abstinent compared to 2 of 29 (6.90%) assigned to placebo (OR = 3.2; 95% CI, 0.60-17.6; P = .17). Psychopathology scores remained stable. Ten serious adverse events occurred (n = 6, varenicline; n = 4, placebo). Abnormal dreams occurred significantly more often in varenicline-treated subjects (n/n = 18/31, 61.3%) than in those receiving placebo (n/n = 9/29, 31%; Fisher exact test, P = .04). Eight varenicline-treated and 5 placebo-assigned subjects expressed fleeting suicidal ideation, a nonsignificant difference.

Conclusions: Varenicline shows efficacy for initiating smoking cessation in bipolar patients, but medication trials of longer duration are warranted for maintaining abstinence. Vigilance for neuropsychiatric adverse events is prudent when initiating varenicline for smoking cessation in this patient population.

Trial Registration: ClinicalTrials.gov identifier: NCT01010204.