Current issues of ACP Journal Club are published in Annals of Internal Medicine


Bupropion alone or with a nicotine patch increased smoking cessation rates

ACP J Club. 1999 July-Aug;131:13. doi:10.7326/ACPJC-1999-131-1-013

Source Citation

Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999 Mar 4;340:685-91.



What is the relative effectiveness of bupropion, a nicotine patch, placebo, and bupropion plus a nicotine patch for smoking cessation?


Randomized, double-blind, placebo-controlled trial with 1-year follow-up.


4 centers in the United States.


893 persons ≥ 18 years of age (mean age 43 y, 52% women), who weighed ≥ 100 lb (≥ 45.4 kg), were motivated to quit smoking, and smoked ≥ 15 cigarettes/d. Exclusion criteria included serious physical or psychiatric illness, pregnancy, lactation, or past nicotine replacement therapy. Follow-up was 80%.


Patients were allocated to 9 weeks of either sustained-release bupropion, 150 mg/d for days 1 to 3 and 300 mg/d for days 4 to 63 (n = 244); a nicotine patch, 21 mg/d for weeks 2 to 7, 14 mg/d for week 8, and 7 mg/d for week 9 (n = 244); bupropion plus a nicotine patch (n = 245); or placebo (n = 160). Patients quit smoking on day 8 and received counseling for 1 year.

Main outcome measures

Self-reported point-prevalence rate of abstinence (abstinence in the previous 7 d and carbon monoxide ≤ 10 ppm) and rate of continuous abstinence (abstinence from quit date and carbon monoxide ≤ 10 ppm), withdrawal symptoms, and weight gain.

Main results

Analysis was by intention to treat. At 1 year, compared with the placebo and nicotine patch-alone groups, the bupropion groups had higher point-prevalence and continuous abstinence rates (P < 0.001) (Table); no difference existed between the 2 bupropion groups (P = 0.22 and P = 0.61, respectively). All 3 active treatments led to less severe withdrawal symptoms than placebo in the first 3 weeks (P < 0.05). Bupropion plus a nicotine patch led to less weight gain than bupropion alone or placebo in the first 7 weeks (P < 0.05).


Compared with placebo or a nicotine patch alone, bupropion alone or with a nicotine patch increased the point-prevalence and continuous smoking cessation rates after 1 year.

Source of funding: Glaxo Wellcome.

For correspondence: Dr. D.E. Jorenby, 1300 University Avenue, Room 7278 MSC, Madison, WI 53706, USA. FAX 608-265-3102.

Table. Comparison of smoking cessation regimens for point-prevalence or continuous abstinence at 1 y*

Outcomes Regimen Intervention Placebo RBI (95% CI) NNT (CI)
Point-prevalence Bupropion 30% 16% 94% (31 to 193) 7 (4 to 16)
Combination† 36% 16% 127% (54 to 240) 5 (4 to 9)
Continuous Bupropion 18% 6% 228% (69 to 548) 8 (5 to 15)
Combination† 22% 6% 229% (108 to 681) 6 (4 to 10)

*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article and from data provided by the author.
†Combination regimen = bupropion plus a nicotine patch.


A nicotine patch plus nicotine nasal spray was more effective than a nicotine patch alone for smoking cessation

Despite higher cigarette prices, tougher anti-smoking laws, and attempts to hold tobacco companies responsible for smoking-related medical costs, smoking cessation remains a huge public health challenge. Blondal and colleagues point out that nicotine patch therapy alone gives an abstinence rate of only 11% after 1 year. Such results have prompted the search for better single or combination smoking cessation therapies, including combined nicotine patch and spray. Unlike previous studies, Blondal and colleagues followed patients for an extended period—6 years. Up to the end of the first year, combination therapy led to a higher abstinence rate than did the patch and placebo spray. Few patients used the spray for up to 1 year. Combination therapy showed a trend toward a higher abstinence rate at 6 years, which suggests a possible long-term benefit.

It is unclear whether the higher success rate of combination therapy was because of higher sustained concentrations of nicotine or a brief effect on concentration of the spray delivery system. The spray quickly provides a dose of nicotine that may relieve temporary cravings associated with relapse of smoking.

Nicotine replacement therapy is one approach to smoking cessation management. Mood is closely related to nicotine consumption. The antidepressant bupropion has been shown to be an effective smoking cessation aid (1). In their well-designed, double-blind, controlled trial, Jorenby and colleagues showed that bupropion, used either alone or in combination with the nicotine patch, was more effective than the patch alone or placebo for smoking cessation. A direct comparison of the 1-year continuous abstinence rates across the 2 studies shows interesting results: The rate for the patch-spray combination in the study by Blondal and colleagues was 27%, which is similar to that for bupropion alone (18.4%) or the bupropion-patch combination (22.5%) in the study by Jorenby and colleagues.

Jorenby and colleagues followed patients for only 1 year. The continuous abstinence rate beyond 1 year still needs to be studied. The fact that such high intermediate-term continuous abstinence rates can be achieved, however, should prompt physicians to consider bupropion in addition, or as an alternative, to nicotine replacement therapy.

Patients in both studies were highly motivated and received adjunctive supportive counseling. These circumstances may not apply to a larger population of persons who smoke and have some desire to quit. Extensive supportive counseling is time-consuming, expensive, and difficult to obtain without access to properly trained professionals. The feasibility and success of these therapies in ambulatory care settings need to be determined.

Another important question that has not been addressed is the effectiveness of antidepressants other than bupropion for smoking cessation. With nicotine replacement therapy already available in patch, spray, and gum forms, evidence of the effectiveness of other mood-altering drugs will add to the smoking cessation management choices available to patients and physicians.

Goutham Rao, MD
University of Pittsburgh Medical Center-St. MargaretPittsburgh, Pennsylvania, USA


1. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997;337:1195-202.