A comparison of sustained-release bupropion and placebo for smoking cessation

N Engl J Med. 1997 Oct 23;337(17):1195-202. doi: 10.1056/NEJM199710233371703.


Background and methods: Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less.

Results: At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups.

Conclusions: A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / administration & dosage*
  • Antidepressive Agents, Second-Generation / adverse effects
  • Bupropion / administration & dosage*
  • Bupropion / adverse effects
  • Delayed-Action Preparations
  • Depression
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / adverse effects
  • Smoking Cessation / methods*
  • Smoking Cessation / statistics & numerical data
  • Substance Withdrawal Syndrome / drug therapy
  • Tobacco Use Disorder / drug therapy
  • Weight Gain / drug effects


  • Antidepressive Agents, Second-Generation
  • Delayed-Action Preparations
  • Bupropion
  • Nicotine