Combined Varenicline With Nicotine Patch for Extended Smoking Cessation

Quick Takes

  • A combination of varenicline and nicotine patches for either 12 or 24 weeks is no more effective than varenicline alone.
  • Side effects including nausea and insomnia ranged between 24% and 30% for either of these common side effects.

Study Questions:

Is a combination of varenicline and nicotine patches effective in increasing smoking cessation effectiveness?


A 2×2 factorial randomized clinical trial study design was used to compare varenicline monotherapy for 12 weeks (n = 315), varenicline plus nicotine patch for 12 weeks (n = 314), varenicline monotherapy for 24 weeks (n = 311), or varenicline plus nicotine patch for 24 weeks (n = 311). Adults who smoked ≥5 cigarettes per day were eligible to participate. The primary outcome of interest was monoxide-confirmed self-reported 7-day point prevalence abstinence at 52 weeks.


A total of 1,251 adults were randomized. The mean age was 49 years, and 54% of participants were women. Of those enrolled, 751 (60.0%) completed treatment and 881 (70.4%) provided final follow-up. There was no significant interaction between the two treatment factors of medication type and medication duration (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.91-1.17). For patients randomized to 24-week vs. 12-week treatment duration, the primary outcome occurred in 24.8% vs. 24.3%, respectively (OR, 1.01; 95% CI, 0.89-1.15). For patients randomized to varenicline combination therapy vs. varenicline monotherapy, the primary outcome occurred in 24.3% vs. 24.8%, respectively (OR, 0.99; 95% CI, 0.87-1.12). The most common side effects included nausea and insomnia.


The investigators concluded that among adults smoking ≥5 cigarettes/day, there were no significant differences in 7-day point prevalence abstinence at 52 weeks among those treated with combined varenicline plus nicotine patch therapy vs. varenicline monotherapy or among those treated for 24 weeks vs. 12 weeks. These findings do not support the use of combined therapy or of extended treatment duration.


This randomized controlled trial does not support the combination of varenicline and nicotine patches for long-term smoking cessation. Determining the most effective methods for long-term smoking cessation may be difficult if factors associated with adherence to smoking cessation vary between smokers.

Clinical Topics: Prevention, Smoking

Keywords: Cigarette Smoking, Duration of Therapy, Nausea, Nicotine, Primary Prevention, Sleep Initiation and Maintenance Disorders, Smoking, Smoking Cessation, Tobacco Smoking, Tobacco Use Cessation Devices, Varenicline

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