Selegiline Helps Smokers Quit

Laurie Barclay, MD

January 23, 2003

Jan. 23, 2003 — Selegiline is effective in aiding smoking cessation, according to the results of a preliminary trial reported in the January issue of Biological Psychiatry. Its effect was about half that of buproprion but comparable to that of nicotine replacement.

"We specifically selected difficult-to-treat smokers because this is the group that hasn't responded to conventional treatments," lead author Tony P. George, MD, from the Yale School of Medicine in New Haven, Connecticut, says in a news release. "While there are several effective treatments for smoking cessation, including nicotine replacement therapies and bupropion (Zyban), there are many smokers who do not respond to these drugs."

Rationale for use of the monoamine oxidase B (MAO-B) inhibitor selegiline hydrochloride was that a component of cigarette smoke is known to inhibit brain MAO activity in smokers, and that inhibition of MAO-B in the brain leads to increases in brain dopamine.

In this study from the Center for Nicotine and Tobacco Use Research and the Transdisciplinary Tobacco Use Research Center (CENTURY/TTURC), 40 smokers meeting DSM-IV criteria for nicotine dependence were randomized to eight weeks of treatment with selegiline, 5 mg orally twice daily, or placebo. All subjects had tried to quit smoking numerous times and had failed.

During the eighth week of the study, nine (45%) of 20 subjects treated with selegiline had stopped smoking for at least seven days, compared with three (15%) of 20 who received placebo (odds ratio [OR], 4.64; 95% confidence interval [CI], 1.02 - 21.00; P < .05). During the last four weeks of the trial, smoking cessation rates were 30% for selegiline and 5% for placebo (OR, 8.14; 95% CI, 0.88 - 75.48; P = .07). At six-month follow-up, seven-day point prevalence smoking cessation rates were reduced compared with the trial endpoint (selegiline, 20%; placebo, 5%; OR, 4.75; 95% CI, 0.48 - 46.91; P = .18).

Smokers with clinically significant depressive symptoms at baseline had worse outcomes for smoking cessation compared with those who did not have significant depression. "This is yet another example of how having comorbid psychiatric symptoms contributes to poorer smoking cessation outcomes," Dr. George says.

Selegiline was well-tolerated, with mild adverse effects including anorexia, gastrointestinal symptoms, and insomnia.

Principal investigator and senior author Stephanie O'Malley, MD, also from Yale School of Medicine, describes this study as "an important contribution to our understanding of the subgroups of people who are not responsive to current treatments."

However, the authors warn that selegiline doses greater than 10 mg/day are associated with increased risk of hypertensive crises, precluding use of this drug in patients with chronic mental illness at high risk for intentional overdose. They recommend larger controlled trials of selegiline and other MAO-B inhibitors for the treatment of nicotine dependence.

Biol Psychiatry. 2003;53:136-143

Reviewed by Gary D. Vogin, MD


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