Improving Treatment Outcomes for Prescription Opioid Dependence

 描述(申请人提供)：阿片类药物依赖是一个严重的公共卫生问题，特别是随着处方阿片类药物(PO)滥用的急剧上升，但长期与美沙酮或丁丙诺啡(BUP)一起维持阿片激动剂可能不是许多PO滥用者的最佳选择。然而，目前的阿片类药物戒毒策略受到高复发率和/或在缓解主观症状方面缺乏有效性的限制。此外，使用纳曲酮(NTX)维持拮抗剂可能是这一人群的最佳长期策略，需要事先阿片类药物戒毒，并与海洛因滥用者相对较差的结果有关。这项应用采用了一种新的、广泛的方法来解决PO依赖的问题，通过确定1)在门诊BUP脱毒期间使用辅助性加巴喷丁(GBP)来改善初始结果，以及2)在脱毒后将PO依赖患者过渡到NTX仓库的可行性，这可能会改善长期结果。GBP是一种低滥用潜能的N型钙通道阻滞剂，可增强阿片类药物的镇痛作用，减少术后吗啡消耗和运动相关疼痛，并逆转对吗啡的抗伤害感受作用。在试点戒毒试验中，GBP在减少渴求和非法阿片类药物使用方面也具有良好的耐受性和有效性。我们建议评估辅助性GBP在BUP辅助戒毒期间的有效性和耐受性，以及随后在PO依赖的参与者中过渡到库NTX治疗的可行性。这项为期8周的随机安慰剂对照临床试验将确定接受门诊BUP戒毒治疗的辅助性GBP I 150 PO依赖者的潜在效用，以及过渡到短期仓库NTX疗法是否可行。我们的三个具体目标是确定(1)GBP在门诊接受BUP戒毒治疗的PO依赖患者中减少阿片类药物渴望和非法使用的有效性和耐受性；(2)TRANTTIN在戒毒后转至NTX库的可接受性和可行性，以及在NTX库的短期维持；以及(3)BUP缩减完成、成功诱导到NTX库的预测指标、症状学和长期结果。目前，FDA批准的唯一治疗阿片戒断的药物是阿片激动剂美沙酮和BUP，这两种药物都有滥用倾向，以及NTX，它可以产生低水平的戒断症状，特别是在治疗的早期。我们的发现，如果阳性，将支持GBP作为一种辅助药物的进一步发展，并为门诊PO依赖治疗提供一种综合、无缝的方法。最终，这项工作可能会通过提供治疗PO依赖的程序性和药理学工具来影响成瘾领域，从而显著改善门诊患者的戒毒结果，并显著增加获得和过渡到NTX治疗的机会。这将改变临床实践，为BUP解毒和建立有效的辅助方案 过渡到NTX治疗的综合方法。对于阿片类药物戒断令人担忧的其他情况，GBP也可能在临床上有用。

 DESCRIPTION (provided by applicant): Opioid dependence is a serious public health problem, particularly with the dramatic rise in prescription opioid (PO) abuse, but long-term opioid agonist maintenance with methadone or buprenorphine (BUP) may not be optimal for many PO abusers. Yet current opioid detoxification strategies are limited by high relapse rates and/or lack of efficacy in relieving subjective symptoms. In addition, antagonist maintenance with naltrexone (NTX), which may be an optimal longer-term strategy for this population, requires prior opioid detoxification and has been associated with relatively poor outcomes in heroin abusers. This application takes a novel, broad approach to address the problem of PO dependence by determining the 1) utility of adjunct gabapentin (GBP) during outpatient BUP detoxification to improve initial outcomes and 2) feasibility of transitioning PO-dependent patients to depot NTX following detoxification, which may improve longer-term outcomes. GBP, an N-type calcium channel blocker with low abuse potential, potentiates opioid analgesia, decreases both postoperative morphine consumption and movement-related pain, and reverses tolerance to the antinociceptive effects of morphine. GBP is also well tolerated and effective in reducing craving and illicit opioid use in pilot detoxification trials. We propose to assess the efficacy and tolerability of adjunct GBP during BUP-assisted detoxification and the feasibility of subsequent transition to depot NTX therapy in PO-dependent participants. This 8-week, randomized, placebo-controlled clinical trial will determine the potential utility of adjunct GBP i 150 PO- dependent individuals undergoing outpatient BUP detoxification and whether transition to short-term depot NTX therapy is feasible. Our three specific aims are to determine (1) the efficacy and tolerability of GBP to reduce craving and illicit use of opioids in PO-dependent individuals undergoing outpatient BUP detoxification; (2) acceptability and feasibility of transitin to, and short-term maintenance on, depot NTX following detoxification; and (3) prognosticators of completion of the BUP taper, successful induction onto depot NTX, symptomatology, and longer-term outcomes. Currently, the only FDA-approved medications for the treatment of opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse liability, and NTX, which can produce low levels of withdrawal-like symptoms, especially early in treatment. Our findings, if positive, will support further development of GBP as an adjunct medication as well as provide an integrated, seamless approach to outpatient PO-dependence treatment. Ultimately, this work could impact the addiction field by providing both procedural and pharmacological tools for treating PO dependence that significantly improve outpatient detoxification outcomes and markedly enhance access and transition to NTX therapy. This would shift clinical practice, establishing an effective adjunct regimen for BUP detoxification and an integrated approach f or transition to NTX therapy. GBP may also be clinically useful for other situations where opioid withdrawal is a concern.