A REVERSIBLE MONOAMINE-OXIDASE-A INHIBITOR (MOCLOBEMIDE) FACILITATES SMOKING CESSATION AND ABSTINENCE IN HEAVY, DEPENDENT SMOKERS

Objective: To assess the effectiveness of moclobemide on smoking cessa tion and abstinence in heavy, dependent smokers. There is a strong ass ociation between smoking and depression, especially in dependent smoke rs. It was hypothesized that smoking is a self-medication to treat dep ression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory proper ties, and smokers have lon er MAO activity than nonsmokers. Methods: W e used a randomized, double-blind, placebo-controlled parallel-group s tudy. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day d uring the third month, was given. Main outcome measures were self-repo rted and biochemically verified (plasma cotinine levels, <20 ng/ml) ab stinence rate. Secondary outcome measures were withdrawal symptoms, Mo ntgomery-Asberg Depression Rating Scale, Hamilton anxiety rating score s, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a meas ure of MAO-A activity. Results: Eighty-eight smokers were randomized t o receive moclobemide (n = 44) or placebo (n = 44). The continuous sel f-reported abstinence rate was higher with moclobemide than with place bo (intention-to-treat analysis until the end point, 6 months: p < 0.0 5; until the end of fellow-up, 1 year: p = 0.09). The abstinence rate according to plasma cotinine levels showed a trend to effectiveness of moclobemide (end point: p = 0.13; follow-up: p = 0.12). Platelet MAO- B activity increased after smoking cessation but without a significant difference. Plasma dihydroxyphenylglycol levels did not change in the placebo group but decreased dose dependently in the moclobemide group . No difference occurred for withdrawal symptoms, Montgomery-Asberg De pression Rating Scale, and Hamilton anxiety scores. Cessation of moclo bemide had no adverse effect. More subjects reported insomnia with moc lobemide (n = 16) than with placebo (n = 3). Conclusion: In this preli minary study, the reversible, selective MAO inhibitor moclobemide faci litated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MA O inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence.