Smoking-Cessation Drugs Do Not Appear To Cause Psychiatric Problems

Compared to placebo, use of varenicline, bupropion or nicotine patches to help smoking cessation does not appear to increase the risk of neuropsychiatric adverse events (NPSAEs), according to a secondary analysis of a large randomized trial.

The EAGLES trial, conducted between 2011 and 2015, had several limitations, Dr. Emma Beard of University College London and colleagues note in a paper in Addiction, and "did not find enough evidence to reject the hypothesis of no difference in neuropsychiatric adverse events compared to placebo."

"Regulators, clinicians and patients," they add, "need to have full information about the direction in which the available evidence points and not just the absence of clear evidence for an effect."

To shed more light on the question, the researchers used Bayes factors to examine the trial data. All of the more than 8,000 trial participants were smokers and about half had psychiatric disorders. Their average age was 47 years.

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Participants were randomized to varenicline (1 mg twice daily), bupropion (150 mg twice daily), nicotine patch (21 mg once daily with taper) or matched placebos. They were then assigned a quitting date to coincide with start of the full dose of varenicline and bupropion and the initiation of nicotine-patch treatment.

The primary endpoint was a composite measure based on post-marketing reports of moderate to severe NPSAEs involving 16 neuropsychiatric symptom categories including aggression, delusions, and hallucination. The secondary safety endpoint consisted of the subset of all NPSAEs that were rated as severe.

For all but two comparisons, say the researchers, "Bayes factors were <1/3, indicating moderate to strong evidence for no difference in risk of NPSAEs between active medications and placebo."

However, they add, "The data were insensitive to confirm whether use of varenicline or bupropion increases the risk of moderate to severe NPSAEs relative to use of placebo among smokers with pre-existing psychiatric conditions, but large differences could be ruled out, and there was very strong evidence of no increase in risk of NPSAEs that were rated severe."

In a statement, Dr. Beard said, "The shadow of psychiatric problems has arguably cost thousands of lives by putting people off using varenicline to help them stop, and doctors off prescribing it. This analysis should provide further reassurance to smokers and clinicians that this is a safe, life-saving drug."

Commenting on the findings by email, senior author Dr. Robert West, also of University College London, told Reuters Health that varenicline "is a highly effective aid to stopping smoking but fear that it may cause serious mental health problems has severely limited its use. This study provides strong support for the idea that the drug does not have such effects."

Varenicline, sold under the brand names Chantix and Champix, is produced by Pfizer. EAGLES was funded by Pfizer and GlaxoSmithKline, a manufacturer of nicotine patches and bupropion (Wellbutrin and Zyban). Dr. Brown has received unrestricted funding from Pfizer. A number of authors are or were employees of Pfizer and of GlaxoSmithKline during the EAGLE trial.

—David Douglas

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