Varenicline may be safe and effective for smoking cessation in bipolar disorder

People with a serious and persistent mental illness such as bipolar disorder are more likely to smoke and to have far lower quit rates than the general population. Early estimated prevalence of smoking among patients with bipolar disorder is more than 65 percent compared with 18 percent among the general public. Quit rates are, on average, 16.6 percent and 42.5 percent, respectively.

Compared with nonsmoking bipolar disorder patients, those who smoke have higher rates of mixed episodes, suicide attempts, and additional drug and alcohol dependence — all of which contribute to lower response rates to conventional mood-stabilizing treatments.

"Smoking cessation is a critically important piece in designing therapeutic programs for people who have a dual diagnosis of depression and addiction. We must address the fact that when bipolar patients have a smoking problem, their mental illness is more difficult to treat," says Mark A. Frye, M.D., chair of the Department of Psychiatry and Psychology at Mayo Clinic's campus in Rochester, Minnesota, and director of the Depression Center there.

So Dr. Frye, in collaboration with smoking cessation clinical researchers Christi A. Patten, Ph.D., a professor of psychology, and Jon O. Ebbert, M.D., from the Nicotine Dependence Center, set out to study the feasibility of using varenicline for patients with bipolar disorder.

Varenicline is an alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist and the first drug to target nicotine receptors. It has proved effective for smoking cessation but is associated with significant psychiatric side effects, including suicidal ideation. In 2014, the Food and Drug Administration reported 34 suicides in the U.S. linked to the drug.

"The reported side effects caused concern about how to study the drug in mental illness, but we felt it was an important study to undertake," Dr. Frye explains. Findings appeared in the December 2013 issue of the Journal of Clinical Psychopharmacology.

Study design and results

Nine participants were initially enrolled in the 12-week Mayo Clinic study. The mean Fagerstrom Test for Nicotine Dependence score was 7, with a mean 15.8 cigarettes smoked a day, and the mean exhaled breath carbon monoxide (CO) was 20. Treatment adherence by pill count was 90 percent.

Four participants eventually dropped out due to adverse medication effects, unrelated injury and worsening of depressive symptoms, but all showed some reduction in cigarette use and two were not smoking at the time they left the study.

The five participants who completed the study showed a significant reduction in the number of cigarettes smoked a day, urge to smoke and CO levels, though only one achieved abstinence, the primary endpoint. There was no significant increase in depressive symptoms or suicidal behavior.

Dr. Frye acknowledges the study's limitations — small sample size and open-label design — but notes that the results suggest that varenicline may help people with bipolar disorder stop smoking with few adverse effects.

Given the high rates of smoking in people with mood and anxiety disorders and potential nicotine withdrawal symptoms, researchers say the study underscores the importance of a comprehensive assessment of mood and anxiety symptoms prior to and during varenicline treatment. A larger study exploring different outcome measures of smoking cessation and mood and anxiety improvement will soon be underway.

For more information

Frye MA, et al. A feasibility study of varenicline for smoking cessation in bipolar patients with subsyndromal depression. Journal of Clinical Psychopharmacology. 2013;33:821.