Naranjo C A, Poulos C X, Bremner K E, Lanctôt K L
Clinical Pharmacology Program and Sociobehavioral Research, University of Toronto, Ontario, Canada.
Clin Pharmacol Ther. 1992 Jun;51(6):729-39. doi: 10.1038/clpt.1992.85.
In previous studies serotonin uptake inhibitors such as citalopram decreased alcohol consumption in alcoholics. The mechanism of the effect is not fully understood. This study tested the hypothesis that it is mediated by changes in desire to drink and alcohol effects. After a 1-week baseline period, subjects (13 men and three women; aged 26 to 69 years; healthy, nondepressed, alcohol-dependent drinkers [mean, 6.6 drinks per day]) were randomized in a double-blind fashion to receive 40 mg/day citalopram and placebo for 1 week each, separated by a 1-week washout period. Daily standard alcoholic drinks (13.6 gm ethanol), nonalcoholic drinks, and tobacco use were recorded; evening urine samples were taken; and interest, desire, craving, and liking for alcohol were rated. Medical status, depression, and anxiety were assessed weekly, but no other treatment or advice was given. Daily alcoholic drinks significantly decreased during citalopram treatment (mean +/- SEM = 4.6 +/- 0.6) compared with placebo (5.7 +/- 0.8; p = 0.01), and the average decrease was 17.5%. Percentage of days abstinent increased during citalopram administration (27.7% +/- 5.7%) compared with placebo (15.5% +/- 3.7%; p less than 0.01). Citalopram decreased interest, desire, craving, and liking for alcohol (all p less than 0.05). There was clear internal validation of these measures in that variations in each correlated with alcohol consumption (all r greater than 0.5, p less than 0.05). Nonalcoholic drinks, self-reports of cigarettes smoked (daily smokers), and body weight did not change significantly. In experimental bar sessions, after the citalopram and placebo periods, subjects were required to consume as many of 18 minidrinks as possible (equivalent to six standard drinks) at 5-minute intervals. Subjects rated their desire for alcohol, intoxication, and mood. Citalopram had no significant effects on the desirability of alcohol or subjective feelings of intoxication. The findings indicate that serotonin uptake inhibitors may act by decreasing the urge to drink and the reinforcing effects of alcohol. Also, a naturalistic outpatient trial is a sensitive, simple, and economic procedure for detecting these drug effects.
在以往的研究中,诸如西酞普兰之类的血清素摄取抑制剂可减少酗酒者的酒精摄入量。其作用机制尚未完全明确。本研究检验了一种假说,即该作用是由饮酒欲望和酒精效应的变化介导的。在为期1周的基线期之后,受试者(13名男性和3名女性;年龄在26至69岁之间;健康、无抑郁、酒精依赖饮酒者[平均每天6.6杯酒])以双盲方式随机分组,分别接受40毫克/天的西酞普兰和安慰剂治疗,各为期1周,中间间隔1周的洗脱期。记录每日标准酒精饮料(13.6克乙醇)、非酒精饮料的摄入量以及烟草使用情况;采集夜间尿液样本;并对饮酒的兴趣、欲望、渴望和喜好程度进行评分。每周评估医学状况、抑郁和焦虑情况,但不给予其他治疗或建议。与安慰剂组(5.7±0.8)相比,西酞普兰治疗期间每日酒精饮料摄入量显著减少(均值±标准误=4.6±0.6;p=0.01),平均减少了17.5%。与安慰剂组(15.5%±3.7%;p<0.01)相比,西酞普兰给药期间戒酒天数的百分比增加(27.7%±5.7%)。西酞普兰降低了对酒精的兴趣、欲望、渴望和喜好程度(所有p<0.05)。这些测量方法有明确的内部验证,因为各项测量值的变化均与酒精摄入量相关(所有r>0.5,p<0.05)。非酒精饮料的摄入量、吸烟情况(每日吸烟者的自我报告)和体重没有显著变化。在实验酒吧环节中,在西酞普兰和安慰剂治疗期之后,要求受试者每隔5分钟尽可能多地饮用18小杯饮料(相当于6标准杯酒)。受试者对饮酒欲望、醉酒程度和情绪进行评分。西酞普兰对饮酒欲望或主观醉酒感受没有显著影响。研究结果表明,血清素摄取抑制剂可能通过降低饮酒冲动和酒精的强化作用来发挥作用。此外,自然主义的门诊试验是检测这些药物效应的一种敏感、简单且经济的方法。