BackgroundDepression is overrepresented in smokers.
ObjectiveTo evaluate smoking abstinence and changes in mood and anxiety levels in smokers with depression treated with varenicline versus placebo.
DesignPhase 4, multicenter, parallel, 1:1 allocation, double-blind, randomization trial. Randomization, stratified by antidepressant use and depression score at baseline, was blocked in sizes of 4. (ClinicalTrials.gov: NCT01078298).
Setting38 centers in 8 countries.
Participants525 adult smokers with stably treated current or past major depression and no recent cardiovascular events.
InterventionVarenicline, 1 mg twice daily, or placebo for 12 weeks, with 40-week nontreatment follow-up.
MeasurementsPrimary outcome was carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9 to 12. Other outcomes included CARs assessed during nontreatment follow-up and ratings of mood, anxiety, and suicidal ideation or behavior.
Results68.4% versus 66.5% of the varenicline and placebo groups, respectively, completed the study. Varenicline-treated participants had higher CARs versus placebo at weeks 9 to 12 (35.9% vs. 15.6%; odds ratio [OR], 3.35 [95% CI, 2.16 to 5.21]; P < 0.001), 9 to 24 (25.0% vs. 12.3%; OR, 2.53 [CI, 1.56 to 4.10]; P < 0.001), and 9 to 52 (20.3% vs. 10.4%; OR, 2.36 [CI, 1.40 to 3.98]; P = 0.001). There were no clinically relevant differences between groups in suicidal ideation or behavior and no overall worsening of depression or anxiety in either group. The most frequent adverse event was nausea (varenicline, 27.0%; placebo, 10.4%). Two varenicline-group participants died during the nontreatment phase.
LimitationsSome data were missing, and power to detect differences between groups was low in rare events. Smokers with untreated depression, with co-occurring psychiatric conditions, or receiving mood stabilizers and antipsychotics were not included.
ConclusionVarenicline increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety.
Primary funding sourcePfizer.