Clinical Edge

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Neuropsychiatric Safety of Smoking Cessation Meds

Lancet; ePub 2016 Apr 22; Anthenelli, Benowitz, et al

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There was no significant increase in neuropsychiatric adverse events associated with varenicline or bupropion relative to nicotine patch or placebo. Varenicline was more effective than placebo, nicotine patch, and bupropion in helping smokers achieve abstinence, and bupropion and nicotine patch were more effective than placebo. This according to study of 8,144 participants who were randomly assigned: 4,116 to the psychiatric cohort and 4,028 to the non-psychiatric cohort. Researchers found:

• In the non-psychiatric cohort, 13 (1.3%) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group, 22 (2.2%) of 989 in the bupropion group, 25 (2.5%) of 1,006 in the nicotine patch group, and 24 (2.4%) of 999 in the placebo group.

• In the psychiatric cohort, moderate and severe neuropsychiatric adverse events were reported in 67 (6.5%) of 1,026 participants in the varenicline group, 68 (6.7%) of 1,017 in the bupropion group, 53 (5.2%) of 1,016 in the nicotine patch group, and 50 (4.9%) of 1,015 in the placebo group.

• Varenicline-treated participants achieved higher abstinence rates than those on placebo (OR=3.61), nicotine patch (OR=1.68), and bupropion (OR=1.75).

• Patients on bupropion and nicotine patch achieved higher abstinence rates than those on placebo (OR=2.07 and 2.15, respectively).

Citation: Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. [Published online ahead of print April 22, 2016]. Lancet. doi:http://dx.doi.org/10.1016/S0140-6736(16)30272-0.

Commentary: Tobacco use remains the most common cause of preventable death in the United States and is responsible for 1 out of every 5 deaths in the US.1 Tobacco cessation is one of the great public health achievements of the last half-century. Half of all adults who have ever smoked have quite and smoking rates have continued to decrease, from 21% in 2005 to 17% in 2014.2 Pharmacologic adjuncts to in-office counseling increase smoking rates by about twofold. Inconsistent data about neuropsychiatric adverse events associated with varenicline and bupropion led the FDA to require the manufacturers of these two medications to conduct a post-marketing randomized trial of safety and efficacy. This randomized trial provides a high degree of reassurance that neither varenicline nor bupropion are associated with important increases in depression or other neuropsychiatric effects, even in patients with psychiatric illness, a group with increased rates of smoking for whom these medications are important. In addition, the study confirms that all the pharmacologic methods studied are effective in increasing smoking cessation rates, with nicotine replacement and bupropion being about twice as effective as placebo and varenocline being about three times as effective. —Neil Skolnik, MD

1. U.S. Department of Health and Human Services. How tobacco smoke causes disease: What it means to you. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010. Accessed May 9, 2016.

2. Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults—United States, 2005—2014. Morbidity and Mortality Weekly Report. 2015;64(44):1233–40. Accessed May 9, 2016.

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