Smoking Cessation: Bupropion or Nortriptyline?
Abstract & Commentary
By Joseph Varon, MD, FACP, FCCP, FCCM, Professor, University of Texas Health Science Center; St. Luke’s Episcopal Hospital, Houston. Dr. Varon reports no financial relationships to this field of study.
Synopsis: Sustained release bupropion treatment is an efficacious aid to smoking cessation for patients at risk for and with chronic obstructive pulmonary disease
Source: Wagena EJ, et al. Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease. Arch Intern Med. 2005;165:2286-2292.
This dutch study was aimed at evaluating efficacy of sustained release bupropion hydrochloride and nortriptyline for smoking cessation among smokers at risk for chronic obstructive pulmonary disease (COPD) and those with COPD. Two hundred-fifty five smokers stratified according to the Global Initiative for COPD guidelines were recruited in a placebo-controlled, double-dummy, randomized trial and assigned in a 1:1 ratio to receive the following: (1) bupropion SR, 150 mg once-a-day, for days 1 through 6, followed by 150 mg twice a day for days 7 through 84; (2) nortriptyline, 25 mg once-a-day for days 1 through 3, followed by 50 mg daily for days 4 through 7, and then 75 mg once-a-day for days 8 through 84; and (3) placebo. At the baseline visit, the target quit date (TQD) was set for the second week, usually day 11 from the start of the medication. The primary outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the TQD. Participants were followed on regular basis and urinary cotinine levels were measured to ascertain abstinence.
Mean age of participants was 51 ± 8.5 years and 51% were women. Prolonged abstinence from smoking was higher in the bupropion SR and the nortriptyline groups as compared to the placebo, although the bupropion SR group and the placebo groups exhibited significant statistical difference. Prolonged abstinence did not differ among genders. Forty participants (16%) discontinued medication because of adverse effects. The rate of discontinuation was statistically significantly higher among the participants receiving nortriptyline. No seizures were reported in any group. Compliance with the medication was poor with approximately 55% of participants using 80% or fewer pills that they were asked to take.
Commentary
Smoking-related disorders continue to be an important cause of morbidity and mortality in this country.1 Many smokers with COPD seem to be at an increased risk for depression.2 It is also well defined that nicotine addiction is often accompanied by comorbid depression or depression symptoms.3 Therefore, using antidepressant agents for smoking cessation seems clinically sound.
The most important finding in this study was the finding that bupropion SR treatment was significantly more efficacious in achieving abstinence compared with placebo. In a subgroup analysis, it also appears that bupropion SR was efficacious in those patients with COPD classified as having depression. Although using nortriptyline also resulted in higher abstinence rates, this difference was not statistically significant. Clearly those patients taking nortriptyline had much higher adverse events and discontinued the medication.
One previous randomized trial has explored the efficacy of antidepressant therapy for smoking cessation in patients with COPD.4 Using bupropion SR, Tashkin and co-workers found a significant effect in abstinence when compared to placebo.
Studies aimed at smoking cessation are very difficult to conduct. Smokers in cessation clinical trials are a self-selected group who are motivated to quit, which may limit the generalization of the findings of this and other smoking cessation studies.
References
1. Xu X, et al. Effects of cigarette smoking on rate of loss of pulmonary function in adults: a longitudinal assessment. Am Rev Respir Dis. 1992;146:1345-1348.
2. Wagena EJ, et. al. Risk of depression and anxiety in employees with chronic bronchitis: the modifying effect of cigarette smoking. Psychosom Med. 2004;66:729-734.
3. Breslau N, Johnson EO. Predicting smoking cessation and major depression in nicotine-dependent smokers. Am J Public Health. 2000;90:1122-1127.
4. Tashkin D, et al. Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial. Lancet. 2001;357: 1571-1575.
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