Wiesbeck G A, Weijers H G, Lesch O M, Glaser T, Toennes P J, Boening J
Addiction Research Group, Department of Psychiatry, University of Wuerzburg, Austria.
Alcohol Alcohol. 2001 Jul-Aug;36(4):329-34. doi: 10.1093/alcalc/36.4.329.
Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiology of alcohol dependence. Its pharmacology, together with encouraging results from both animal studies and clinical trials with cocaine users, led us to postulate that flupenthixol would significantly prevent relapse in detoxified alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel groups and appropriate statistical evaluation. Subjects met criteria for moderate to severe alcohol dependence (DSM-III-R), without any concomitant psychiatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m. injection every second week for 6 months on an out-patient basis, followed by 6 months of follow-up. Efficacy was based on absolute abstinence, with relapse being defined as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with more, relapses. Though well tolerated, relapse rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant difference from the medication. Flupenthixol was also inferior to placebo with regard to other secondary criteria of efficacy (cumulative abstinence duration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstinence maintenance in alcohol-dependent individuals.
氟哌噻吨具有广泛的受体作用谱，可与多种多巴胺和血清素结合位点相互作用，这些位点在酒精依赖的神经生物学中起着重要作用。其药理学特性，以及动物研究和针对可卡因使用者的临床试验所取得的令人鼓舞的结果，使我们推测氟哌噻吨能显著预防已戒酒的酒精依赖个体复发。我们进行了一项前瞻性、随机、双盲、安慰剂对照、多中心试验，设有两个平行组并进行了适当的统计学评估。研究对象符合中度至重度酒精依赖（DSM-III-R）标准，且无任何并发精神障碍。在完全戒酒之后，281名男女患者被随机分为两组，一组每两周接受一次10毫克癸酸氟哌噻吨肌肉注射，另一组接受安慰剂注射，为期6个月的门诊治疗，随后进行6个月的随访。疗效基于绝对戒酒情况，复发定义为在纳入研究后饮用任何酒精。与假设相反，氟哌噻吨并未减少复发，反而与更多的复发相关。尽管耐受性良好，但治疗6个月后的复发率分别为85.2%（氟哌噻吨组）和65.5%（安慰剂组），药物组之间存在高度显著差异。在其他次要疗效标准（累积戒酒持续时间、12个月后的复发率）方面，氟哌噻吨也不如安慰剂。这些结果表明，10毫克剂量的癸酸氟哌噻吨对酒精依赖个体的戒酒维持并无有益作用。
