Quitting Smoking When the Nicotine Patch Is Not Enough

Summary and Comment |
June 30, 2014

Quitting Smoking When the Nicotine Patch Is Not Enough

  1. Joel Yager, MD

For men and heavy smokers who couldn't quit smoking with the nicotine patch, varenicline plus bupropion outperformed varenicline alone.

  1. Joel Yager, MD

Quitting cigarette smoking is difficult, even with nicotine patches. In a two-stage, controlled trial, 349 community-recruited smokers used the nicotine patch for 1 week; 221 nonresponders (46% men; mean cigarettes/day, 21; mean years of smoking, 26) were randomized to 12 weeks of varenicline (0.5 mg/day for 3 days; gradually increased to 1.0 mg twice daily by day 8) alone or with bupropion (150 mg/day for 3 days; 150 mg twice daily thereafter). The authors have financial interests in smoking cessation technologies.

Abstinence was determined by self-report confirmed by expired-air CO measurements. About 36% of participants dropped out, with similar numbers in each arm. Intent-to-treat analyses at study completion showed superiority for combined treatment (40%; varenicline alone, 26%). Combination treatment was more effective in men (odds ratio, 4.26), heavy smokers (≥20 cigarettes/day; OR, 2.29), and participants with high dependence ratings (OR, 3.51). Abstinence was associated with weight gain (mean, 2.84 kg; with combined treatment, 3.05 kg). No other treatment-attributable adverse effects were noted. Six months after treatment, gains were generally sustained, but at lower levels.


Notably, men responded better than women, perhaps due to previously observed sex-related differences in striatal nicotine and dopamine D2/D3 receptor regulation.

Will these effects persist? A previous study (NEJM Journal Watch Gen Med Jan 28 2014) reported sustained benefits for varenicline plus bupropion only among those who smoked >20 cigarettes/day (52-week abstinent rates, 32% vs. 17% for varenicline monotherapy). In that study, combined treatment was associated with greater anxiety (7% vs. 3% with monotherapy) and depression (4% vs. 1%). It would be useful to ascertain whether combined treatment is equally safe and effective for cigarette-dependent patients being medicated for schizophrenia, mood disorders, and other psychiatric comorbidities.

Editor Disclosures at Time of Publication

  • Disclosures for Joel Yager, MD at time of publication Grant /Research support AHRQ Editorial boards Bulletin of the Menninger Clinic; Eating Disorders: Journal of Treatment and Prevention; Eating Disorders Review (Editor-in-Chief); International Journal of Eating Disorders; UpToDate; FOCUS: The Journal of Lifelong Learning in Psychiatry Leadership positions in professional societies American Psychiatric Association (Chair, Council of Quality Care)


Reader Comments (1)

J Ross Hester, PA-CH Other Healthcare Professional, Psychiatry, Edcom Associates Holistic Health
Competing Interests: My practice seeks to integrate both cognitive, NLP/hynosis/CBT, and psychiatric therapies.

As as Psych PA and hypnotist who has roughly twice the success rate these authors describe, I have come to two conclusions: 1. That many smokers int this group are self-medicating with nicotine's stimulant effect for premorbid undiagnosed ADHD or dysthymia, and do better when hese conditions are correctly diagnosed and treated. This may partly explain his study's improved rsults wih combined therapy. 2. Despite current reimbursement limits, the behavioral aspects of smoking and normal resistance to change cannot be divorced from the psychopharmacologic factors addressed in this study.

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