Effects of Varenicline on Smoking Cessation in Adults With Stably Treated Current or Past Major Depression: A Randomized Trial

Study Questions:

Are mood and anxiety levels changed by treatment with varenicline among smokers who are abstinent from smoking?


Data from a phase 4, multicenter, double-blind, randomized, control trial (38 centers in 8 countries) were used for the present analysis. Randomization was stratified by antidepressant use and depression score at baseline. The study population included 525 adult smokers with stably treated current or past major depression and no recent cardiovascular events. Varenicline, 1 mg twice daily, or placebo was given for 12 weeks, with a 40-week nontreatment follow-up. The primary outcome of interest was carbon monoxide–confirmed continuous abstinence rate (CAR) for weeks 9-12. Additional outcomes included CARs assessed during nontreatment follow-up and ratings of mood, anxiety, and suicidal ideation or behavior. Limitations existed; for instance, some 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.


Of 646 persons screened, 525 smokers with major depressive disorder (ages 19-73 years) were randomly assigned into the study, and all received study treatment. Fewer participants discontinued varenicline than placebo (21.5% vs. 30.9%; p = 0.017). Overall study discontinuation rates were similar across treatment groups (31.6% vs. 33.5%), with 68.4% versus 66.5% of the varenicline and placebo groups, respectively, completing the study. Baseline demographic, smoking history, and psychiatric characteristics were similar between groups. On average, participants had smoked for 26.7 years, smoking 22 cigarettes daily in the past month. Varenicline-treated participants had higher CARs versus placebo at weeks 9-12 (35.9% vs. 15.6%; odds ratio [OR], 3.35; 95% confidence interval [CI], 2.16-5.21; p < 0.001), 9-24 (25.0% vs. 12.3%; OR, 2.53; CI, 1.56-4.10; p < 0.001), and 9-52 (20.3% vs. 10.4%; OR, 2.36; CI, 1.40-3.98; 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.


The investigators concluded that varenicline increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety.


Based on the data provided in this study, varenicline for smoking cessation among smokers with depression appears to be a reasonable choice. However, this trial did have several limitations, and the study population was limited to those with stable depression or past depression.

Keywords: Depressive Disorder, Major, Quinoxalines, Smoking Cessation, Suicidal Ideation

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