Effect of Varenicline on Smoking Cessation Through Smoking Reduction | Clinical Trial - Varenicline for Smoking Cessation


The goal of the trial was to evaluate treatment with varenicline versus placebo on achieving smoking abstinence through gradual smoking reduction.

Contribution to the Literature: This trial showed that varenicline resulted in higher rates of smoking abstinence.

Study Design

Current smokers were randomized to varenicline titrated to 1 mg twice daily (n = 760) versus placebo (n = 750). The study drug was initiated at 0.5 mg daily for 3 days, then 0.5 mg twice daily for days 4-7, and then maintenance dose of 1 mg twice daily. The study drug was administered for 24 weeks. Subjects were asked to reduce their smoking 50% by week 4, 75% by week 8, and quit by week 12.

  • Blinded, parallel, placebo

Inclusion criteria:

  • Age ≥18 years
  • Smoked an average of 10 or more cigarettes per day
  • Not able or willing to quit in the next month, but willing to make a quit attempt over 3 months

Exclusion criteria:

  • Suicide attempt or suicidal behavior
  • Major depressive or anxiety disorder
  • Psychosis, panic disorder, post-traumatic stress disorder, schizophrenia
  • Alcohol or substance abuse in the last year
  • Severe chronic obstructive pulmonary disease
  • Clinically significant cardiovascular or cerebrovascular disease in the last 2 months
  • Pregnant or likely to become pregnant
  • Total number of enrollees: 1,510
  • Duration of follow-up: 1 year
  • Mean patient age: 45 years
  • Percentage female: 44%

Principal Findings:

The primary outcome, self-reported abstinence during 15-24 weeks, occurred in 32.1% of the varenicline group versus 6.9% of the placebo group (p < 0.05).

Secondary outcomes:

  • Self-reported abstinence during 21-52 weeks: 27.0% vs. 9.9% (p < 0.05), respectively
  • Study adverse events (including nausea, abnormal dreams, insomnia, constipation, vomiting, and weight gain): 82.3% vs. 72.5%, respectively
  • Suicidal ideation or behavior: 0.8% vs. 1.3%, respectively


Among smokers, who were otherwise healthy and not able or willing to quit smoking abruptly, the use of varenicline increased smoking abstinence through gradual smoking reduction. Smoking cessation is an important topic, and the results of this trial should help to provide more treatment options for providers. Unfortunately, these findings do not apply to patients with active cardiovascular or cerebrovascular disease since these were important exclusion criteria.


Ebbert JO, Hughes JR, West RJ, et al. Effect of Varenicline on Smoking Cessation Through Smoking Reduction: A Randomized Clinical. JAMA 2015;313:687-694.

Clinical Topics: Prevention, Smoking

Keywords: Smoking, Smoking Cessation, Tobacco Use Cessation Products, Primary Prevention, Nausea, Vomiting, Weight Gain, Constipation, Suicidal Ideation, Sleep Initiation and Maintenance Disorders, Benzazepines, Quinoxalines

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