JAMA Psychiatry：氨己烯酸治可卡因依赖或疗效差

　　近期，美国一项评估氨己烯酸治疗可卡因依赖安全性和有效性的研究并未发现氨己烯酸组与安慰剂组之间存在取决于治疗方案（protocol-defined）的疗效差异，其原因或许是受试者对治疗的依从性差或氨己烯酸疗效较差。该项研究论文4月10日在线发表于《美国医学会杂志•精神病学》（JAMA Psychiatry）。

　　可卡因依赖是一个值得关注的健康问题，但目前还没有经过验证的药物治疗方案，墨西哥一项单中心双盲研究曾证明了氨己烯酸的有效性。该研究的目的是在一个美国样本中评估氨己烯酸治疗可卡因依赖的安全性和有效性。

　　该研究为多中心、随机、双盲、安慰剂对照临床试验，在美国11个地区进行，为期12周，在13、16、20和24周进行随访。研究共纳入186名受试者，均为寻求治疗的可卡因依赖者（平均年龄45岁），约67%为男性，约60%是非裔美国人。受试者接受每日两次的氨己烯酸（总剂量，3.0g/日）或安慰剂治疗，另加每周计算机认知行为治疗、双周个别咨询。通过权变管理（Contingency management）激励受试者提供尿样。研究中主要终点指标为，以自我报告和药物定量尿检方法评估的在过去两周内可卡因戒断的患者比例。每周可卡因使用天数以及1～13周内尿样无药物的次数为次要终点指标。

　　研究结果表明，主要终点指标（P=0.67）、次要终点指标（P＞ 0.99）以及其他终点指标在氨己烯酸组与安慰剂组之间无显著差异。然而，尽管超过66%的受试者（＞63%的氨己烯酸组受试者）服用了超过70%的药物，但之后的尿液氨己烯酸浓度水平显示大约40%～60%的患者对于服用氨己烯酸没有依从性，这种依从性的缺乏可能会掩盖氨己烯酸的疗效。研究未发现受试者出现视力下降和视野异常。

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A Multisite, Double-blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Vigabatrin for Treating Cocaine Dependence.
IMPORTANCE
Cocaine dependence is a significant public health problem, yet no validated pharmacological treatment exists. The potent γ-aminobutyric acid (GABA)ergic medication vigabatrin has previously been shown to be effective in a double-blind single-site study conducted in Mexico. OBJECTIVE To evaluate the safety and efficacy of vigabatrin for the treatment of cocaine dependence in a US sample.
DESIGN AND SETTING
Multisite, randomized, double-blind, placebo-controlled, 12-week clinical trial with follow-up visits at weeks 13, 16, 20, and 24 in 11 US sites. PARTICIPANTS In total, 186 treatment-seeking participants with cocaine dependence (mean age, 45 years). Approximately 67% were male, and about 60% were of African American race/ethnicity.
INTERVENTIONS
Participants received twice-daily doses of vigabatrin (total dosage, 3.0 g/d) or matched placebo, plus weekly computerized cognitive behavioral therapy and biweekly individual counseling for 13 weeks. Contingency management encouraged the provision of urine samples.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was the proportion of participants with cocaine abstinence during the last 2 weeks of the 12-week treatment phase as assessed by self-reports and quantitative urine drug screens. The weekly fraction of cocaine use days and the number of drug-free urine samples during weeks 1 through 13 were key secondary measures. RESULTS No significant differences were observed between the vigabatrin group and the placebo group on the primary outcome measure (P = .67), key secondary measures (P > .99), or other outcome measures. However, while pill counts and self-reports indicated that more than 66% of all participants (and >63% of the vigabatrin group) took more than 70% of their medication, post hoc vigabatrin urine concentration levels suggested that approximately 40% to 60% of patients taking vigabatrin may not have been adherent. This lack of adherence may have obscured any evidence of vigabatrin efficacy. No visual acuity or visual field deterioration occurred in any of the participants.
CONCLUSIONS AND RELEVANCE
No protocol-defined differences in efficacy between vigabatrin treatment and placebo were detected for any outcome variable. This may have been due to medication nonadherence or, alternatively, due to the weak efficacy of vigabatrin. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00611130.