Varenicline appears efficacious for smoking cessation in patients treated for current or past depression

Varenicline appeared to help patients with stably treated current or past depression stop smoking without increasing depression or anxiety, according to a new industry-funded study.

Varenicline is a nicotinic receptor partial agonist that has demonstrated efficacy in assisting some patients with smoking cessation. However, several studies have suggested that varenicline may be associated with adverse neuropsychiatric symptoms, raising concerns about its use in patients with mood disorders or other psychiatric conditions.

To evaluate both efficacy and safety, researchers performed a phase 4 multicenter, randomized, double-blind trial in adult smokers who had stably treated current or past major depression but had not had a recent cardiovascular event. The goal of the trial was to compare the effect of varenicline versus placebo on smoking cessation as well as on mood and anxiety levels.

Patients were randomly assigned to receive varenicline, 1 mg twice daily, or placebo for 12 weeks. Follow-up without treatment lasted for 40 weeks. The study's primary outcome was continuous abstinence rate confirmed by carbon monoxide testing for weeks 9 to 12, while secondary outcomes included continuous abstinence rate during the nontreatment follow-up, mood, anxiety, and suicidal ideation/behavior. The study was funded by Pfizer and appeared in the Sept. 17 Annals of Internal Medicine.

Two hundred fifty-six patients were assigned to receive varenicline and 269 were assigned to receive placebo. Participants had smoked for an average of 26.7 years and had smoked an average of 22 cigarettes per day in the past month. Most patients (62.7%) were women. Overall, 68.4% of the varenicline group and 66.5% of the placebo group finished the study. Patients who took varenicline had higher continuous abstinence rates than those who took placebo at weeks 9 to 12 (35.9% vs. 15.6%; odds ratio [OR], 3.35; P<0.001), weeks 9 to 24 (25.0% vs. 12.3%; OR, 2.53; P<0.001) and weeks 9 to 52 (20.3% vs. 10.4%; OR, 2.36; P=0.001). The two groups did not have any clinically relevant differences in suicidal ideation or behavior, overall worsening of depression or overall worsening of anxiety.

A total of 72.3% of varenicline participants and 66.9% of placebo participants reported adverse effects, most of which were rated mild or moderate. Nausea, which was reported by 27.0% of the varenicline group and 10.4% of the placebo group, was the most common overall, and the most common adverse effects causing treatment discontinuation were depression (2.0% in the varenicline group and 1.1% in the placebo group) and depressed mood (0% in the varenicline group and 1.5% in the placebo group). Two patients in the varenicline group had serious psychiatric adverse effects (i.e., psychotic disorder, depression, and suicidal ideation) and four placebo participants had intentional self-injury, depression and suicidal ideation, agitation, and depression. Two patients died during the nontreatment phase, both in the varenicline group; their deaths were considered unrelated to the study treatment.

The authors acknowledged that some data were missing because of attrition and that the study had limited power to detect differences between groups in rare events. In addition, the study did not include patients who smoked and had untreated depression, those with co-occurring psychiatric episodes, or those taking mood stabilizers or antipsychotics. However, they concluded that treatment with varenicline improved smoking cessation rates in patients who had stably treated current or past depression and did not increase depression or anxiety.

“With 350 million individuals having [depression] worldwide and because many smokers who seek treatment have a lifetime history of [major depression disorder], these results have the potential to reduce morbidity and mortality in many smokers,” the authors wrote. They stressed that clinicians should use caution, however, when treating smoking cessation in depressed patients with “more complex psychiatric presentations.”