Injectable, sustained-release naltrexone for the treatment of opioid dependence - A randomized, placebo-controlled trial
Injectable, sustained-release naltrexone for the treatment of opioid dependence - A randomized, placebo-controlled trial
复制标题
DOI：
10.1001/archpsyc.63.2.210
复制
发表时间：
2006-02-01
影响因子：
--
通讯作者：
O'Brien, CP
中科院分区：
文献类型：
--
作者：
Comer, SD;Sullivan, MA;O'Brien, CP
背景：口服纳洛酮可完全拮抗阿片受体激动剂的作用。然而，纳洛酮依从性差一直是有效治疗阿片类药物依赖的主要障碍。目的：评价纳洛酮缓释贮库制剂治疗阿片类药物依赖的安全性和有效性。设计和设置：随机、双盲、安慰剂对照、8周试验，在2个医学中心进行。参与者：60名海洛因依赖成人。干预措施：参与者按性别和海洛因使用年数（>= 5 vs <5）分层，然后随机接受安慰剂或192或384 mg贮库型纳洛酮。在第1周和第5周开始时给药。所有参与者每周接受两次复发预防治疗，提供观察的尿液样本，并在每次访视时完成其他评估。主要结果测量：治疗保留率和阿片类药物阴性尿液样本的百分比。治疗中的保留与剂量相关，安慰剂组、192 mg纳洛酮组和384 mg纳洛酮组分别有39%、60%和68%的患者，在2个月结束时继续治疗。剂量对脱落时间有显著的主效应，安慰剂组、192 mg纳洛酮组和384 mg纳洛酮组的平均脱落时间分别为27、36和48天。阿片类药物、美沙酮、可卡因、苯二氮卓类药物和苯丙胺阴性尿样的百分比随剂量变化显著。当在不假设缺失尿样为阳性的情况下重新计算数据时，除可卡因外，未发现任何测试药物的组主效应，安慰剂组可卡因阴性尿样的百分比较低。不良事件极少，一般为轻度。这种配方的纳洛酮耐受性良好，并产生了强大的，剂量相关的增加治疗retention.Conclusion：这些数据提供了新的证据的可行性，疗效和耐受性的持久的拮抗剂治疗阿片类药物依赖。
Context: Oral naltrexone can completely antagonize the effects produced by opioid agonists. However, poor compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence.Objective: To evaluate the safety and efficacy of a sustained release depot formulation of naltrexone in treating opioid dependence.Design and Setting: Randomized, double-blind, placebo-controlled, 8-week trial conducted at 2 medical centers.Participants: Sixty heroin-dependent adults.Interventions: Participants were stratified by sex and years of heroin use (>= 5 vs < 5) and then were randomized to receive placebo or 192 or 384 mg of depot naltrexone. Doses were administered at the beginning of weeks 1 and 5. All participants received twice-weekly relapse prevention therapy, provided observed urine samples, and completed other assessments at each visit.Main Outcome Measures: Retention in treatment and percentage of opioid-negative urine samples.Results: Retention in treatment was dose related, with 39%, 60%, and 68% of patients in the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively, remaining in treatment at the end of 2 months. Time to dropout had a significant main effect of dose, with mean time to dropout of 27, 36, and 48 days for the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively. The percentage of urine samples negative for opioids, methadone, cocaine, benzodiazepines, and amphetamine varied significantly as a function of dose. When the data were recalculated without the assumption that missing urine samples were positive, a main effect of group was not found for any drugs tested except cocaine, where the percentage of cocaine-negative urine samples was lower in the placebo group. Adverse events were minimal and generally mild. This formulation of naltrexone was well tolerated and produced a robust, dose-related increase in treatment retention.Conclusion: These data provide new evidence of the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence.