In a trial among people with a history of depression, those taking the quit-smoking aid varenicline - marketed in the U.S. as Chantix - were no more prone to depression or thoughts of suicide than those on a placebo, according to a new study.
In 2007, the U.S. Food and Drug Administration (FDA) announced reports of serious side effects including suicidal thoughts and erratic behavior in some people taking Chantix to stop smoking. The agency and Chantix manufacturer Pfizer said at the time it was unclear whether the symptoms were caused by the drug or by nicotine withdrawal.
Two years later, the FDA added a "black box warning" about these possible side effects to packages of Chantix and to another drug prescribed for smoking cessation, Zyban.
But the new trial results showing no greater depression risk while quitting smoking with Chantix, even in depression-prone patients, are not surprising according to lead study author Dr. Robert Anthenelli of the Veterans Affairs San Diego Healthcare System in California.
"Our prior experience using the medication in smokers with and without mental health disorders, and the results of more than 15 placebo-controlled randomized clinical trials found no such association," he said.
About half of smokers seeking help in quitting are depressed or have suffered from depression and related disorders in the past, Anthenelli's team points out in the Annals of Internal Medicine. Yet previous trials of drugs to aid smoking cessation have generally excluded people taking antidepressants or antipsychotic drugs to treat mental disorders, they write.
To test whether varenicline would help such patients quit smoking without exacerbating depression, Anthenelli and his fellow researchers, many of whom work for Pfizer, randomly assigned 525 adult smokers to take varenicline or a placebo.
All the trial participants had stable treated current or past major depression and no recent cardiovascular problems. They ranged in age from 18 to 79 and two thirds were women.
About three quarters of participants regularly used antidepressants and antianxiety drugs during the study, but people using other smoking-cessation medications, non-cigarette tobacco products or marijuana were excluded, as were people taking antipsychotic medications.
During the three-month treatment phase of the study, half the participants took Chantix, 1 milligram twice daily, and the other half got dummy pills. Afterwards, all participants were followed for 40 weeks during which they no longer took the pills.
During the final month of taking the drug or placebo, participants took breath tests to detect carbon monoxide and verify whether they had abstained from smoking. Among those taking Chantix, 35 percent had not smoked, compared to 15 percent of the placebo group.
Previous studies have found that Chantix is "very effective" for quitting smoking, Anthenelli noted. Smokers who take the medication, are two to three times more likely to successfully quit long-term than those who take a placebo, he said.
Participants taking Chantix were more likely to suffer from mild side effects like nausea, headache and abnormal dreams, and twice as many on Chantix reported insomnia compared to the placebo group. But there were no significant differences in mood or anxiety between groups and no worsening of depression in either group, according to the results.
Researchers monitored mood changes during the treatment phase and suicidal thinking or behavior for an additional 40 weeks after smokers stopped taking the medication.
At the beginning of the study 88 people in the group taking varenicline reported any lifetime history of suicidal thoughts or attempts compared to 89 people in the placebo group.
At the start of the study, 6 people in the varenicline group and one in the placebo group had suicidal thoughts.
During the final 30 days of the three-month treatment phase, 15 people taking varenicline and 19 on placebo reported suicidal thoughts, and one placebo participant exhibited suicidal behavior.
There were two deaths among the participants during the 40-week follow up - one caused by an accidental fall and the other by an overdose of morphine and another prescription medication.
It's uncertain whether that overdose, which involved one of the participants who took varenicline, was a suicide, according to the researchers. But it happened 10 weeks after participants stopped taking varenicline, so the death was not considered treatment related, the authors write.
The study was funded by Pfizer and Anthenelli and some of his coauthors were supported by funding from the U.S. National Institutes of Health and other sources.
"This study addresses a critical gap in the literature by targeting smokers with major depression," said Brian Hitsman, who studies cigarette smoking and depression at Northwestern University Feinberg School of Medicine in Chicago.
Smokers with depression would be especially vulnerable to any mood changes as a result of the drug, Hitsman said.
These results combined with other studies over the last five years make a solid argument that Chantix does not worsen stable and treated depression, he said.
But the drug's effects for people with untreated depression could be different, and need to be studied as well, he cautioned.
Most smokers are not at an increased risk of depressive episodes after quitting, Anthenelli said.
"However, because depression is an episodic illness prone to recurrence, and since a minority of smokers with past histories of depression may be at increased risk after quitting, it's important for clinicians to remain vigilant and monitor their patients closely," he said.
People with depression are more likely to start smoking than others, and smokers with a history of depression are more likely to have severe withdrawal symptoms than those without depression, Anthenelli said.
"The bottom line is that close monitoring is still required when using varenicline to treat smokers with mental illness, even those with major depression, but it's becoming increasingly clear that varenicline is safe and well-tolerated in this underserved population," Hitsman said.