No Apparent Increase in Neuropsychiatric Side Effects From Smoking Cessation Mediations Interview with:

Robert M. Anthenelli, M.D. Professor and Executive Vice Chair Director, Pacific Treatment and Research Center Department of Psychiatry University of California, San Diego, Health Sciences

Dr. Robert Anthenelli

Robert M. Anthenelli, M.D.
Professor and Executive Vice Chair
Director, Pacific Treatment and Research Center
Department of Psychiatry
University of California, San Diego, Health Sciences What is the background for this study?

Dr. Anthenelli: Despite growing evidence to the contrary, significant concerns have been raised about the neuropsychiatric safety risk of the smoking cessation medications, varenicline and bupropion. What has been lacking until now among individuals with and without psychiatric disorders is a large, randomized controlled trial that directly compares these medications with placebo and an active comparator (nicotine patch) and that systematically probes for neuropsychiatric adverse events while smokers are trying to quit. What are the main findings?

Dr. Anthenelli:

1) Neither varenicline nor bupropion significantly increased incidence of moderate-to-severe neuropsychiatric adverse events relative to placebo or nicotine patch in smokers without or with stable psychiatric disorders.

2) Regardless of treatment condition, smokers with a history of or a current stable psychiatric disorder reported more neuropsychiatric adverse events than their counterparts without such conditions.

3) Varenicline was more effective than placebo, nicotine patch, and bupropion in helping smokers achieve abstinence; bupropion and nicotine patch were more effective than placebo.

4) While quit rates overall were slightly lower in smokers with psychiatric disorders compared with cessation rates in individuals without these conditions, all three medications were more effective than placebo, and their relative efficacy (varenicline > bupropion = nicotine patch > placebo) was the same in this special population of smokers as it was for smokers without mental health disorders.

EAGLES is the first trial to have compared the smoking cessation efficacy of the three, first-line smoking cessation medications in smokers with current or past psychiatric disorders. These results are important because individuals with mental health conditions are disproportionately affected by smoking-related diseases and death. What should clinicians and patients take away from your report?

Dr. Anthenelli:

1) In the context of a growing body of studies finding no evidence of a greater incidence of serious neuropsychiatric adverse events in users of varenicline and bupropion compared with nicotine replacement therapy or placebo, it appears these non-nicotine medications can be used safely by psychiatrically stable smokers.

2) Smokers with a history of or current stable psychiatric disorder are more prone to exhibit such events regardless of the medication used and should be monitored during a quit attempt.

3) Varenicline demonstrates superior efficacy to bupropion and nicotine patch, but all three medications are more effective than placebo in smokers with and without stable psychiatric disorders. What recommendations do you have for future research as a result of this study?

Dr. Anthenelli: We are looking forward to conducting secondary analyses of the large EAGLES dataset to examine, in finer detail, the safety and efficacy of the three first-line medications in sub-cohorts (e.g., smokers with major depressive disorder, bipolar disorder, and schizophrenia) of the psychiatric cohort. We will also be examining predictors of treatment response to determine whether these vary as a function of a smoker’s psychiatric history. Thank you for your contribution to the community.


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

Anthenelli, Robert M et al.

The Lancet , Volume 0 , Issue 0 , Published Online: 22 April 2016


Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on April 27, 2016 by Marie Benz MD FAAD