Improving Clinical Outcomes in Treating Heroin Dependence Randomized, Controlled Trial of Oral or Implant Naltrexone
Improving Clinical Outcomes in Treating Heroin Dependence Randomized, Controlled Trial of Oral or Implant Naltrexone
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DOI：
10.1001/archgenpsychiatry.2009.130
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发表时间：
2009-10-01
影响因子：
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通讯作者：
Tait, Robert J.
中科院分区：
文献类型：
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作者：
Hulse, Gary K.;Morris, Noella;Tait, Robert J.
背景：口服盐酸纳曲酮能有效拮抗海洛因，但由于患者不遵医嘱，其效用受到限制。缓释制剂可以克服这一限制。目的：比较单次纳曲酮缓释植入与每日口服纳曲酮的安全性和有效性。设计：70名海洛因依赖志愿者参加了一项随机、双盲、双安慰剂对照试验，随访期为6个月。患者：入选标准为DSM-IV阿片样物质（海洛因）依赖；18岁或以上；随机化的意愿；居住在西澳大利亚州珀斯市区；完成临床前筛选和书面同意。总共确定了129名符合条件的参与者，其中70名（54%）提供了知情同意，并根据研究设计随机分组。干预：参与者接受口服纳曲酮，50mg /d，为期6个月（加上安慰剂植入物）或单剂量2.3 g纳曲酮植入物（加上安慰剂片）。主要观察指标：(1)纳曲酮治疗水平维持在2 ng/mL以上；(2)恢复正常海洛因使用（>= 4 d/周）；（三）其他海洛因使用和戒毒的；(4)使用非法非阿片类药物；(5)阿片类药物过量需要住院治疗的人数；(6)与治疗相关的意外和预期不良事件；(7)活性纳曲酮植入物接受者的血液纳曲酮水平（即药代动力学特征）。结果：口服组和种植组在第1个月和第2个月血液纳曲酮水平低于2 ng/mL （P < 0.001）和2个月（P = 0.01）；此外，更多的口服组参与者在6个月后恢复正常海洛因使用（P = 0.003），并且在早期阶段（中位数[SE]， 115[12.0]天对158[9.4]天）。有10个与试验相关的意外不良事件。一个严重的不良事件，伤口血肿，与手术植入有关。男性纳曲酮血药浓度分别维持在1和2 ng/mL以上101天（95%可信区间83-119）和56天（39-73），女性纳曲酮血药浓度分别维持在124天（88-175）和43天（16-79）。结论：与口服纳曲酮相比，纳曲酮种植体可有效减少常规海洛因使用的复发，且与主要不良事件无关。
Context: Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation.Objective: To compare the safety and efficacy of a single-treatment sustained-release naltrexone implant with daily oral naltrexone treatment.Design: Seventy heroin-dependent volunteers entered a randomized, double-blind, double-placebo controlled trial with a 6-month follow-up period.Patients: Eligibility criteria were DSM-IV opioid (heroin) dependence; age 18 years or older; willingness to be randomized; residing in the Perth, Western Australia, metropolitan area; and completion of preclinical screening and written consent. A total of 129 eligible participants were identified, and 70 (54%) provided informed consent and were randomized as per the study design.Intervention: Participants received oral naltrexone, 50 mg/d, for 6 months (plus placebo implants) or a single dose of 2.3 g of naltrexone implant (plus placebo tablets).Main Outcome Measures: (1) Maintaining therapeutic naltrexone levels above 2 ng/mL; (2) return to regular heroin use (>= 4 d/wk); (3) other heroin use and abstinence; (4) use of illicit nonopioid drugs; (5) number of opiate overdoses requiring hospitalization; (6) treatment-related unexpected and expected adverse events; and (7) blood naltrexone levels (ie, pharmacokinetic profile) for recipients of active naltrexone implants.Results: More participants in the oral vs the implant group had blood naltrexone levels below 2 ng/mL in months 1 (P < .001) and 2 (P = .01); in addition, more oral group participants had returned to regular heroin use by 6 months (P = .003) and at an earlier stage (median [SE], 115 [12.0] days vs 158 [9.4] days). There were 10 trial-related, unexpected adverse events. One serious adverse event, a wound hematoma, was associated with surgical implantation. Naltrexone blood levels in implant recipients were maintained above 1 and 2 ng/mL for 101 (95% confidence interval, 83-119) and 56 (39-73) days, respectively, among men and 124 (88-175) and 43 (16-79) days among women.Conclusions: The naltrexone implant effectively reduced relapse to regular heroin use compared with oral naltrexone and was not associated with major adverse events.