FDA to Remove, Update Boxed Warnings on Mental Health Side Effects of Chantix, Zyban

The Food and Drug Administration (FDA) announced Friday that it will remove the boxed warning related to serious mental health side effects from the smoking cessation medication Chantix (varenicline). The language describing the serious mental health side effects seen in patients quitting smoking will also be removed from the boxed warning in the Zyban (bupropion) label. (Because the active ingredient in Zyban is in the antidepressant class, the label carries the class boxed warning for suicidality and antidepressants. This language will remain in a boxed warning for Zyban and other bupropion products.) The announcement was made after a large clinical trial found such risks were lower than previously suspected.

The FDA previously requested that the manufacturers of Chantix and Zyban conduct a clinical trial to evaluate the neuropsychiatric safety of the medications in patients without and with a history of psychiatric disorders. The trial enrolled over 8,000 patients in 16 countries who took Chantix (1 mg twice daily), Zyban (150 mg twice daily), nicotine replacement therapy (NRT), or placebo for 12 weeks, followed by a non-treatment phase of 12 weeks. 

Clinically significant neuropsychiatric adverse events occurred at a similar frequency across treatment arms in patients without psychiatric diagnoses (3.1% to 3.5% in the treatment groups versus 4.1% in placebo group). There was a higher incidence of neuropsychiatric adverse events in patients with psychiatric diagnoses who took Chantix and Zyban (11.8% to 12.2% versus 9.5%). The results of the trial also confirmed that Chantix and Zyban were superior to placebo in promoting smoking abstinence regardless of a person’s mental health history.

“The risk of these mental health side effects is still present, especially in those currently being treated for mental illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental illnesses in the past,” the FDA announced. “However, most people who had these side effects did not have serious consequences such as hospitalization.” Therefore, the FDA believes that this trial confirms that the benefits of taking these drugs for smoking cessation outweigh the risk of neuropsychiatric adverse events.

Still, the agency cautioned that patients taking Chantix or Zyban should stop taking the medication if they notice significant side effects while on the medication. Patients and health care professionals are encouraged to report side effects involving Chantix, Zyban, or other medications to the FDA MedWatch program. 

For related information, see the Psychiatric News article “Large Population Study Does Not Link Varenicline With Suicide, Psychosis, or Traffic Incidents.”