The psychiatric side effects of a popular quit-smoking drug make it too dangerous to use as a first attempt to kick the habit, according to a new study. The authors suggest the drug should eventually be taken off the market altogether.
The new study on the safety of varenicline (Chantix), appearing in the journal PLoS One, found that when compared with other smoking-cessation treatments, including nicotine replacement and the antidepressant bupropion (Zyban), varenicline was associated with significantly more cases of suicide, self-injury and depression. Varenicline was linked to 90% of 3,249 reported cases of self-harm or depression in people using quit-smoking drugs between 1998 and 2010, the study found, compared with 3% for nicotine replacement and 7% for bupropion.
The current report isn’t the first to note the potential side effects of varenicline. After it was approved by the U.S. Food and Drug Administration (FDA) in 2006, reports of related adverse events increasingly emerged, leading the agency to put a black box warning on its label in 2009. The warning noted the “risk of serious mental health events including changes in behavior, depressed mood, hostility, and suicidal thoughts” in varenicline users. The label change also applied to bupropion.
But Dr. Curt Furberg, professor of health sciences at Wake Forest Baptist Medical Center and an author of the latest study, notes that his analysis found that varenicline resulted in many more cases of mental disturbances than bupropion. Given its safety profile, he argues that varenicline should be used only as a last resort for smokers who have tried other methods — including behavior modification, nicotine replacement and bupropion — and still can’t quit.
The Veterans Affairs Administration already uses varenicline by these guidelines, and Furberg approves of the policy. “They got it right,” he says. “They have restricted use of Chantix to a last-resort drug. They say when you try to get people to quit, and if you need a drug, start off with nicotine replacement and then Zyban. If they don’t work, then use Chantix. But if you do, you need to monitor mental status to see if people are suicidal in any way.”
In October, the FDA conducted a review of data on neuropsychiatric problems and varenicline, and concluded that the benefits of the drug outweighed the risks for smokers trying to quit. The agency found that the drug’s existing black-boxed label was a sufficient warning. But Furberg characterized the FDA’s review as “flawed” because it relied on two studies of hospitalizations associated with varenicline’s use, which “could not capture most of the serious psychiatric side effects, including suicide, depression, aggression and assaults. These can be catastrophic events but do not normally result in hospitalization.”
Citing the FDA’s conclusion, Pfizer, which makes varenicline, said in a statement that “clinical data to date do not show that Chantix causes these events,” referring to neuropsychiatric conditions. The company is currently conducting a large-scale study of the safety of its drug, focusing on the risk of suicidal behavior and depression, and expects to release results in 2017.
As for the drug’s effectiveness, Pfizer’s initial studies showed that 44% of smokers who began a 12-week treatment program on varenicline had quit after three months, but fewer were able to remain smoke-free. Other studies have shown that after one year, about 22% of varenicline users had successfully kicked their smoking habit.
Earlier this year, Furberg also reported on heart-related problems associated with varenicline, as well as the drug’s tendency to cause blackouts in some users. Based on these results, the Federal Aviation Administration banned varenicline use among its pilots and air traffic controllers, and the military has prohibited its pilots and missile crews from using the drug as well. Truck drivers are restricted from using the medication while on the road.
Given the latest evidence, Furberg believes the current warning on varenicline needs to be strengthened, and that doctors and would-be quitters should be cautioned not to use the drug as a first-line treatment. Adding an additional warning is important because many physicians don’t follow the latest studies on the drug, and may not be aware that compared with other stop-smoking options, varenicline carries a higher risk of suicidal behavior and depression. Having that information on the label would help doctors to make more informed decisions, says Furberg, and possibly save smokers from harming themselves.
“I’m for smoking cessation,” he says, a former smoker himself. “But with a benefit so disappointingly low, and adverse effects that are piling up — blackouts, aggression, heart events, suicide and depression — the bad things outweigh the small good effect of the drug. So what we are saying is we should restrict its use.”
Alice Park is a writer at TIME. Find her on Twitter at @aliceparkny. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.