A large international study has concluded that two smoking-cessation drugs sold by Pfizer and GlaxoSmithKline do not significantly increase the risk of serious neuropsychiatric adverse events, raising the possibility that their black-box removing could be removed.

The Lancet-published EAGLES study investigated use of Pfizer’s Chantix/Champix (varenicline) and bupropion (GSK’s Zyban but now generically available) compared to a placebo or a nicotine patch in 8,144 adult smokers, around half of which had a history of psychiatric disorders.

The study did not show a significant increase in neuropsychiatric adverse events attributable to either drug relative to the control arms. Pfizer’s drug was more effective than placebo, nicotine patch, and buprion in helping smokers achieve abstinence, whereas buprion and nicotine patch were found to be more effective than placebo, according to the data.

The primary safety endpoint was defined as the occurrence of at least one treatment-emergent severe adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment-emergent moderate or severe adverse event of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behaviour or completed suicide.

The incidence of the primary safety endpoint in patients without a history of psychiatric disorders was 1.3 percent for Chantix/Champix, 2.2 percent for buprion, 2.5 percent for the nicotine patch and 2.4 percent for placebo, while the incidence rates in patients with a history of psychiatric disorders were 6.5 percent, 6.7 percent, 5.2 percent and 4.9 percent, respectively.

Both drugs currently carry strong warnings of serious neuropsychiatric adverse events reported in some patients attempting to quit smoking while taking them in the post-marketing experience.

“Smoking cessation support is often underutilised, due in part to misperceptions about the effectiveness and safety of smoking cessation medicines,” noted lead study investigator Robert  Anthenelli, Professor of Psychiatry at the University of California. “This study offers important new information to prescribers and smokers to help them make an informed decision about smoking cessation treatment options.”