The Food and Drug Administration (FDA) ordered Pfizer, which makes Chantix, and GlaxoSmithKline, maker of Zyban, to place a warning highlighting the "risk of serious mental health events" when taking the drugs, including behavior changes, depression, hostility and suicidal thoughts.
"The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking," said Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research.
Doctors prescribing the two smoking-cessation drugs should also monitor their patients for any unusual mood or behavioral changes after the medicines are taken, she added.
However, Woodcock stressed that the products "are effective aids in helping people quit" smoking, the leading cause of preventable disease and death in the United States.
Pfizer said it had updated its labeling of Chantix using the FDA guidelines, noting it had made the information available "immediately" to US healthcare providers and patients.
"The benefits of Chantix outweigh the risks for many patients when used as directed," Briggs Morrison, a senior vice president at Pfizer, said in a statement.
Although the cause for the association between the drugs and the mental problems was unknown, the FDA said that some of the symptoms may be due to patients experiencing nicotine withdrawal, although some patients experienced the symptoms while still smoking.
The FDA also required the manufacturers to conduct a clinical trial to determine how often patients using smoking cessation therapies experience serious neuropsychiatric symptoms, noting that the agency had not found a clear link between the medications and suicidal events.