Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial

Ann Intern Med. 2013 Sep 17;159(6):390-400. doi: 10.7326/0003-4819-159-6-201309170-00005.

Abstract

Chinese translation

Background: Depression is overrepresented in smokers.

Objective: To evaluate smoking abstinence and changes in mood and anxiety levels in smokers with depression treated with varenicline versus placebo.

Design: Phase 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).

Setting: 38 centers in 8 countries.

Participants: 525 adult smokers with stably treated current or past major depression and no recent cardiovascular events.

Intervention: Varenicline, 1 mg twice daily, or placebo for 12 weeks, with 40-week nontreatment follow-up.

Measurements: Primary 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.

Results: 68.4% 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.

Limitations: 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.

Conclusion: Varenicline increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety.

Primary funding source: Pfizer.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use
  • Anxiety
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Depressive Disorder, Major / complications*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / psychology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / therapeutic use*
  • Quinoxalines / adverse effects
  • Quinoxalines / therapeutic use*
  • Smoking Cessation / methods*
  • Smoking Cessation / psychology*
  • Suicidal Ideation
  • Treatment Outcome
  • Varenicline
  • Young Adult

Substances

  • Antidepressive Agents
  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Varenicline

Associated data

  • ClinicalTrials.gov/NCT01078298