Berlin I, Saïd S, Spreux-Varoquaux O, Launay J M, Olivares R, Millet V, Lecrubier Y, Puech A J
Department of Clinical Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.
Clin Pharmacol Ther. 1995 Oct;58(4):444-52. doi: 10.1016/0009-9236(95)90058-6.
To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers. There is a strong association between smoking and depression, especially in dependent smokers. It was hypothesized that smoking is a self-medication to treat depression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non-smokers.
We used a randomized, double-blind, placebo-controlled parallel-group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day during the third month, was given. Main outcome measures were self-reported and biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate. Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a measure of MAO-A activity.
Eighty-eight smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The continuous self-reported abstinence rate was higher with moclobemide than with placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05; until the end of follow-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 Depression Rating Scale, and Hamilton anxiety scores. Cessation of moclobemide had no adverse effect. More subjects reported insomnia with moclobemide (n = 16) than with placebo (n = 3).
In this preliminary study, the reversible, selective MAO inhibitor moclobemide facilitated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MAO inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence.
评估吗氯贝胺对重度、成瘾性吸烟者戒烟及保持戒烟状态的有效性。吸烟与抑郁症之间存在密切关联，尤其是在成瘾性吸烟者中。据推测，吸烟是一种治疗抑郁症的自我疗法。香烟烟雾具有单胺氧化酶（MAO）抑制特性，吸烟者的MAO活性低于非吸烟者。
我们采用了一项随机、双盲、安慰剂对照的平行组研究。给予安慰剂或吗氯贝胺，前2个月每天400毫克，第3个月每天200毫克。主要结局指标为自我报告的及经生化验证（血浆可替宁水平，<20纳克/毫升）的戒烟率。次要结局指标为戒断症状、蒙哥马利-阿斯伯格抑郁评定量表、汉密尔顿焦虑评分、血小板MAO-B活性以及作为MAO-A活性指标的血浆二羟基苯乙二醇。
88名吸烟者被随机分为接受吗氯贝胺组（n = 44）或安慰剂组（n = 44）。吗氯贝胺组持续自我报告的戒烟率高于安慰剂组（意向性分析至终点，6个月：p < 0.05；至随访结束，1年：p = 0.09）。根据血浆可替宁水平得出的戒烟率显示吗氯贝胺有疗效趋势（终点：p = 0.13；随访：p = 0.12）。戒烟后血小板MAO-B活性增加，但无显著差异。安慰剂组血浆二羟基苯乙二醇水平未变化，而吗氯贝胺组呈剂量依赖性降低。戒断症状、蒙哥马利-阿斯伯格抑郁评定量表及汉密尔顿焦虑评分方面无差异。停用吗氯贝胺无不良影响。报告使用吗氯贝胺出现失眠的受试者（n = 16）多于使用安慰剂者（n = 3）。
在这项初步研究中，可逆性、选择性MAO抑制剂吗氯贝胺促进了高度成瘾性吸烟者戒烟。需要对更多吸烟者进行进一步研究，以评估MAO抑制剂在高尼古丁成瘾性吸烟者戒烟及保持戒烟状态中的作用。
