Johnson Bankole A, Roache John D, Ait-Daoud Nassima, Javors Martin A, Harrison Joseph M, Elkashef Ahmed, Mojsiak Jurij, Li Shou-Hua, Bloch Daniel A
Department of Psychiatric Medicine, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623, USA.
Drug Alcohol Depend. 2006 Oct 1;84(3):256-63. doi: 10.1016/j.drugalcdep.2006.02.011. Epub 2006 May 2.
Prior studies have demonstrated inefficacy among dopamine receptor antagonists for treating cocaine dependence. An alternative approach would be to investigate the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such as the 5-HT(3) receptor antagonist ondansetron, to reduce cocaine's reinforcing effects. We hypothesized that ondansetron might be more efficacious than placebo at reducing cocaine intake and promoting abstinence in cocaine-dependent individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63 treatment-seeking, cocaine-dependent men and women received ondansetron (0.25 mg, 1.0 mg, or 4.0 mg twice daily) or placebo. Up to three times per week, participants were assessed on several measures of cocaine use, including urine benzoylecgonine. Cognitive behavioral therapy was administered weekly. Ondansetron was well tolerated, causing no serious adverse events. The ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups and a greater rate of improvement in percentage of participants with a cocaine-free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0 mg group had a lower rate of improvement in percentage of weekly mean non-use days than did placebo recipients (p = 0.04). These results suggest the possibility of a non-linear dose-response function, with evidence supporting efficacy for the 4.0 mg group.
先前的研究已证明多巴胺受体拮抗剂在治疗可卡因依赖方面无效。另一种方法是研究间接抑制皮质-中脑边缘多巴胺释放的药物的作用，比如5-羟色胺(3)受体拮抗剂昂丹司琼，看其是否能降低可卡因的强化作用。我们假设昂丹司琼在减少可卡因依赖个体的可卡因摄入量和促进戒断方面可能比安慰剂更有效。在一项为期10周的随机、双盲、对照试验试点中，63名寻求治疗的可卡因依赖男性和女性接受了昂丹司琼（每日两次，剂量分别为0.25毫克、1.0毫克或4.0毫克）或安慰剂治疗。参与者每周接受多达三次的可卡因使用情况评估，包括尿液中苯甲酰爱康宁的检测。每周进行认知行为疗法治疗。昂丹司琼耐受性良好，未引起严重不良事件。在所有治疗组中，4.0毫克剂量的昂丹司琼组脱落率最低，与安慰剂组相比，可卡因戒断周数的参与者改善率更高（p = 0.02），而1.0毫克剂量的昂丹司琼组每周平均不使用天数的改善率低于安慰剂组（p = 0.04）。这些结果表明存在非线性剂量反应函数的可能性，有证据支持4.0毫克剂量组的疗效。
