Sustained-Release Naltrexone for Opioid Dependence: Longitudinal Study in Humans

描述（由申请人提供）：除了持续存在的海洛因滥用问题外，处方类阿片滥用已成为一个严重的公共卫生问题。虽然目前存在几种治疗阿片类药物依赖的药物，但与使用相关的各种问题使得寻找替代形式的药物治疗变得重要。纳曲酮是一种阿片类拮抗剂，目前可口服，已被批准用于治疗阿片类药物依赖。然而，不遵医嘱一直是有效治疗的主要障碍。在我们之前的研究中，我们证明了一种可注射的纳曲酮储存库制剂可以有效地对抗海洛因3-5周，这取决于剂量。随后的一项随机、安慰剂对照临床试验进一步表明，该药的治疗保留率以剂量相关的方式增加，安慰剂组39%的患者，192毫克纳曲酮组60%的患者，384毫克纳曲酮组68%的患者在2个月的研究期结束时仍在接受治疗。这些结果支持这种治疗阿片类药物依赖的策略的安全性和有效性。当前应用中描述的研究旨在评估更持久的纳曲酮植入式制剂的效果。纳曲酮植入物在减少海洛因的镇痛、呼吸、主观和性能影响方面的安全性、有效性和作用持续时间将在人体中进行测量。重要的是，在当前的应用中，可能伴随阿片受体长期阻断的心理和行为变化也将被测量。具体地说，冲动行为将在纳曲酮植入之前和之后反复测量。这种纳曲酮制剂的可用性为我们提供了一个独特的机会，可以在纵向研究中前瞻性地确定阿片受体本身的阻断是否与冲动行为的减少有关，以及阻断的丧失是否与冲动恢复到基线水平有关。

DESCRIPTION (provided by applicant): In addition to the ongoing problem of heroin abuse, prescription opioid abuse has been emerging as a serious public health concern. Although several medications currently exist for treating opioid dependence, various problems associated with their use make the search for alternative forms of pharmacotherapy important. Naltrexone, an opioid antagonist that is currently available in oral form, is approved for the treatment of opioid dependence. However, medication non-compliance has been a major obstacle to effective treatment. In our previous research, we demonstrated that an injectable depot formulation of naltrexone was effective in antagonizing heroin for 3-5 weeks, depending on dose. A subsequent randomized, placebo-controlled clinical trial of this medication further showed that treatment retention increased in a dose-related fashion, with 39% of patients in the placebo group, 60% of patients in the 192 mg naltrexone group, and 68% of patients in the 384 mg naltrexone group remaining in treatment at the end of the 2-month study period. These results support the safety and effectiveness of this strategy for the treatment of opioid dependence. The study described in the current application is designed to evaluate the effects of an even longer-lasting implantable formulation of naltrexone. The safety, effectiveness, and duration of action of the naltrexone implant in reducing the analgesic, respiratory, subjective, and performance effects of heroin will be measured in humans. Importantly, the psychological and behavioral changes that may accompany long-term blockade of opioid receptors will also be measured in the current application. Specifically, impulsive behavior will be measured before and repeatedly after administration of the naltrexone implant. The availability of this formulation of naltrexone provides us with the unique opportunity to determine prospectively in a longitudinal study whether blockade of opioid receptors per se is associated with reductions in impulsive behavior and whether loss of blockade is associated with a return to baseline levels of impulsivity.