A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence
A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence
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DOI：
10.1016/j.drugalcdep.2006.02.011
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发表时间：
2006-10-01
影响因子：
4.2
通讯作者：
Bloch, Daniel A.
中科院分区：
文献类型：
--
作者：
Johnson, Bankole A.;Roache, John D.;Bloch, Daniel A.
先前的研究已经证明多巴胺受体拮抗剂治疗可卡因依赖无效。另一种方法是研究皮质-中脑边缘多巴胺释放的间接抑制剂（如5-HT 3受体拮抗剂昂丹司琼）降低可卡因强化作用的能力。我们假设昂丹司琼可能比安慰剂更有效地减少可卡因摄入量和促进可卡因依赖者的戒断。在一项为期10周的随机双盲对照试验中，63名寻求治疗的可卡因依赖男性和女性接受了昂丹司琼（0.25 mg，1.0 mg或4.0 mg，每日两次）或安慰剂。每周最多三次，对参与者进行可卡因使用的几项措施评估，包括尿苯甲酰爱贡宁。认知行为疗法每周进行一次。恩丹西酮耐受性良好，未引起严重不良事件。在所有治疗组中，昂丹司琼4.0 mg组的脱落率最低，与安慰剂组相比，无可卡因周参与者的百分比改善率更高（p = 0.02），而昂丹司琼1.0 mg组每周平均未使用天数的百分比改善率低于安慰剂组（p = 0.04）。这些结果表明可能存在非线性剂量-反应函数，有证据支持4.0 mg组的疗效。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
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-HT3 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 (0.25mg, 1.0mg, or 4.0mg 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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.