Naranjo C A, Poulos C X, Bremner K E, Lanctot K L
Psychopharmacology Research Program, Sunnybrook Health Science Centre, University of Toronto, Canada.
Int Clin Psychopharmacol. 1994 Sep;9(3):163-72. doi: 10.1097/00004850-199409000-00004.
Several serotonin uptake inhibitors, including the long-acting fluoxetine, have been found to decrease alcohol intake in moderately dependent alcoholics. While the mechanism of their effect is not fully elucidated, a previous study with citalopram indicated that decreased desire to drink may be an important factor. Therefore, we tested fluoxetine effects on alcohol intake and desire to drink in a placebo-controlled study. Subjects, recruited by advertisement, were mildly/moderately dependent alcoholics (12 male, four female, aged 19-59 years, healthy, non-depressed) who did not believe they had a drinking problem and were not requesting treatment. After a 1 week baseline they received, single-blind, 2 weeks placebo followed by 2 weeks fluoxetine 60 mg/day. As out-patients, subjects recorded daily standard drinks (13.6 g ethanol) and rated interest, desire, craving and liking for alcohol biweekly. Each out-patient period was immediately followed by a double-blind experimental drinking session. Out-patient daily drinks slightly decreased during fluoxetine to 6.6 +/- 0.9 (mean +/- S.E.M.) compared with during placebo (7.16 +/- 0.95, p = 0.07, N.S.) and baseline (7.18 +/- 1.0, p > 0.1, N.S.). Desire, interest and craving for alcohol decreased during fluoxetine vs placebo baseline (p < 0.05), but not vs placebo. Appetite loss and decrease in food intake (p < 0.01, fluoxetine vs placebo) correlated with each other (r = 0.91, p < 0.01) but neither correlated with decrease in alcohol intake (appetite: r = 0.26, N.S.; food intake: r = 0.22, N.S.). Weight loss occurred during fluoxetine (p < 0.05 vs placebo) but did not correlate with decrease in alcohol intake (r = 0.1, N.S.). In the experimental drinking sessions after placebo and fluoxetine treatments subjects rated their desire for each of 18 mini-drinks (each one-third of a standard drink) offered at 5 min intervals. Fluoxetine decreased desire to drink throughout the sessions; both mean and maximum desire ratings were lower after fluoxetine than after placebo (ANOVA, p < 0.05). Therefore, fluoxetine seems to have a robust effect on decreasing desire for alcohol. We propose that in the absence of intention by subjects to reduce drinking, their habitual drinking patterns mitigated against reduced consumption in the out-patient phase. However, fluoxetine could be a useful adjunct for patients in a treatment context who are motivated to reduce their drinking.
包括长效氟西汀在内的几种血清素摄取抑制剂已被发现可减少中度酒精依赖者的酒精摄入量。虽然其作用机制尚未完全阐明，但先前一项关于西酞普兰的研究表明，饮酒欲望降低可能是一个重要因素。因此，我们在一项安慰剂对照研究中测试了氟西汀对酒精摄入量和饮酒欲望的影响。通过广告招募的受试者为轻度/中度酒精依赖者（12名男性，4名女性，年龄19 - 59岁，健康，无抑郁），他们不认为自己有饮酒问题且未寻求治疗。经过1周的基线期后，他们接受单盲治疗，先服用2周安慰剂，然后服用2周氟西汀，剂量为每日60毫克。作为门诊患者，受试者记录每日标准饮酒量（13.6克乙醇），并每两周对饮酒的兴趣、欲望、渴望和喜好进行评分。每个门诊期之后紧接着是一个双盲实验饮酒环节。与服用安慰剂期间（7.16±0.95，p = 0.07，无统计学意义）和基线期（7.18±1.0，p＞0.1，无统计学意义）相比，服用氟西汀期间门诊患者的每日饮酒量略有下降，降至6.6±0.9（平均值±标准误）。与安慰剂基线期相比，服用氟西汀期间对酒精的欲望、兴趣和渴望降低（p＜0.05），但与安慰剂相比无此差异。食欲减退和食物摄入量减少（氟西汀组与安慰剂组相比，p＜0.01）相互关联（r = 0.91，p＜0.01），但两者均与酒精摄入量的减少无关（食欲：r = 0.26，无统计学意义；食物摄入量：r = 0.22，无统计学意义）。服用氟西汀期间出现体重减轻（与安慰剂相比，p＜0.05），但与酒精摄入量的减少无关（r = 0.1，无统计学意义）。在安慰剂和氟西汀治疗后的实验饮酒环节中，受试者对每隔5分钟提供的18小份酒（每份为标准饮酒量的三分之一）的欲望进行评分。氟西汀在整个环节中降低了饮酒欲望；氟西汀治疗后的平均和最大欲望评分均低于安慰剂治疗后（方差分析，p＜0.05）。因此，氟西汀似乎对降低饮酒欲望有显著作用。我们认为，在受试者无意减少饮酒的情况下，他们的习惯性饮酒模式不利于门诊阶段饮酒量的减少。然而，对于有动机减少饮酒量的治疗中的患者，氟西汀可能是一种有用的辅助药物。
