New trial data reported in the Lancet may alleviate some concerns regarding the risk of neuropsychiatric events and smoking cessation medications. The trial, which assessed the efficacy and safety of these treatments, is the largest to date, and was requested by the FDA following concerns about the neuropsychiatric safety of varenicline and bupropion.
The study screened 11,186 participants who smoke at least 10 cigarettes a day (total median number was 21); 8,144 (73%) were randomly assigned to a non-psychiatric cohort or a psychiatric cohort. The psychiatric cohort (n=4074) included patients that met the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for mood (2882, 72%), anxiety (782, 19%), psychotic (386, 9%), and borderline personality disorders (24, <1%). The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events.
Results showed the overall incidence of the primary endpoint events was similar across the four treatment groups: varenicline 4.0% (80 of 2016 participants), bupropion 4.5% (90 of 2006 participants), nicotine patch 3.9% (78 of 2022 participants), and placebo 3.7% (74 of 2014 participants). There were more neuropsychiatric adverse events in the psychiatric cohort (5.8%, 238 of 4074 participants) than the non-psychiatric cohort (2.1%, 84 of 3984 participants; P<0.0001 for the cohort effect). In the psychiatric cohort, moderate to severe adverse psychiatric events were slightly higher (varenicline 6.5%, bupropion 6.7%, nicotine patch 5.3%, placebo 4.9%).
In abstinence comparisons varenicline showed superior efficacy to nicotine patch, bupropion and placebo at end of treatment (weeks 9–12) and follow-up (weeks 9–24). Overall, in weeks 9–12, the abstinence rate for varenicline was 33.5%, and for weeks 9–24 it was 21.8%. For bupropion, nicotine patch and placebo the rates were 22.6% and 16.2%, 23.4% and 15.7%, and for placebo 12.5% and 9.4%, respectively.
While the risk difference in the incidence of serious neuropsychiatric adverse events for varenicline and bupropion was not significantly higher than placebo, the authors note that psychiatric patients trying to quit smoking are likely to have more confounding factors in treatment and appear to have a harder time quitting.
They concluded that, “in the context of evidence from clinical trials and observational cohort studies, this large, multinational trial provides further evidence that varenicline and bupropion can be used safely by psychiatrically stable smokers.”
For more information visit TheLancet.com.