As Pfizer Pharmaceuticals pays out millions of dollars in claims related to depression and suicide associated with the antismoking drug Chantix, a study published September 13 in AJP in Advance found that the drug may be no more harmful than other smoking-cessation therapies.
Researchers in the Department of Psychiatry at the University of Chicago and at Columbia University conducted the largest randomized controlled trial to date evaluating the safety and efficacy of varenicline— a nicotine receptor partial agonist and the active ingredient in the product Chantix.
J. John Mann, M.D. (left), and Robert Gibbons, Ph.D., reanalyzed previous data concerning varenicline and found it was not linked to suicide events, depression, or aggression.
Courtesty of Columbia University and University of Chicago
According to study authors J. John Mann, M.D., and Robert Gibbons, Ph.D., since the Food and Drug Administration issued a black-box warning for Chantix in 2009, varenicline has been extensively studied for its association with neuropsychiatric events, but results have been inconsistent, and the studies have had major limitations.
“There are very few meta-analyses evaluating the effect of varenicline at a personal level,” Mann told Psychiatric News. He said that it is important to conduct more studies in clinical settings with limited exclusionary criteria, which will allow assessments of more-realistic outcomes. “In reality, we see people who want to quit smoking with unstable diabetes, heart disease, taking medication for 10 different conditions. Conducting randomized controlled trials in the clinic is important because the patterns of findings may be different.”
Mann, who is the Paul Janssen Professor of Translational Neuroscience in Psychiatry at Columbia, explained that the current study used “a highly optimized design that is rarely employed”—a reevaluation of the most pivotal randomized controlled trials of varenicline to thoroughly investigate the causes of psychiatric episodes of each participant.
With information from more than 40,000 subjects, the authors reanalyzed data from 17 placebo-controlled trials conducted by Pfizer to assess smoking abstinence, suicidal ideation, depression, aggression, and nausea in participants with and without a history of psychiatric illness. In addition, data from the Department of Defense were evaluated to compare the rates of neuropsychiatric events and psychiatric symptoms among military health system patients receiving varenicline or nicotine-replacement therapy.
The data showed that varenicline was highly associated with inducing nausea among patients, but not with suicide events, depression, or aggression. Current or past psychiatric illness increased the risk of neuropsychiatric events equally among the varenicline and placebo groups.
In the drug-comparison studies, the rate of neuropsychiatric events in the varenicline cohort was significantly less than in those receiving nicotine-replacement therapy. Overall, varenicline was more successful in achieving smoking abstinence than placebo or alternative smoking-cessation therapies.
“While varenicline is known to be effective, doctors and patients have been reluctant to prescribe varenicline because of concerns regarding its association with neuropsychiatric events,” said Gibbons, director of the Center for Health Statistics at the University of Chicago. He noted that the study added to the literature by showing that increased risk for psychiatric symptoms is not found when studies look at a highly diverse population. “Based on these findings, clinicians who were concerned that varenicline increased the risk of neuropsychiatric events should reconsider its use,” Gibbons added.
When Psychiatric News asked Mann why he thinks thousands of varenicline users have reported adverse psychiatric effects, he replied, “People who smoke have more pronounced aggressive and impulsive traits—smoking is associated with suicidal behavior and mood change—[and] sometimes the side effects or adverse effects reported are due to nicotine withdrawal or the loss of the cognitive-enhancing effects of nicotine.”
Mann also noted that when any medication receives negative media attention for adverse events, clinicians are more likely to inquire about these side effects, and patients are more likely to report them. “Some reports are due to the patient being alert to the possibility [of a side effect] and [thus] more likely to report its occurrence, and sometimes the person feels that they have the complication, but objective examination fails to confirm this,” Mann said.
The study was funded by the National Institute of Mental Health. Gibbons served as an expert witness for Pfizer in a case related to varenicline and neuropsychiatric adverse events. Pfizer provided no financial support. ■