Improved Strategies for Outpatient Opioid Detoxification

描述(申请人提供)：从事阿片依赖治疗的临床医生和临床研究人员面临着明显的临床迫切需要改进戒毒策略，以避免早期复发和反复需要戒毒的模式，这是该领域目前治疗努力的特点。虽然用美沙酮或丁丙诺啡维持激动剂是确保长期治疗保留的最有效战略，但阿片类药物替代疗法对许多阿片成瘾者来说是不可接受的，特别是那些最近确诊的阿片成瘾者或越来越多的处方阿片滥用者，他们往往不愿承诺多年的阿片类药物维持。在7天或28天内逐步减少丁丙诺啡剂量的努力迄今收效甚微。在丁丙诺啡停药后加入阿片受体拮抗剂纳曲酮是提高阿片类药物脱毒成功率的一种新策略。在目前的临床实践中，要求住院患者戒毒才能接受纳曲酮诱导，这构成了阿片类拮抗剂治疗的一个重大障碍，因为患者无法接受，以及住院治疗的保险限制不断增加。研究人员使用以拮抗剂为基础的阿片依赖治疗的丰富经验支持了实施门诊纳曲酮诱导程序的可行性。最近推出的纳曲酮长效注射制剂，目前正在寻求FDA批准其治疗阿片类药物依赖，这使得这一应用特别及时。在丁丙诺啡逐渐减少阿片类药物戒毒方法后，需要明确的指导方针才能有效地诱导纳曲酮的使用。拟议的研究将寻求1)通过添加纳曲酮来改善丁丙诺啡逐渐戒毒方法的长期结果，以及2)开发一种使用丁丙诺啡和低剂量纳曲酮开始治疗的程序，以允许门诊患者诱导使用长效纳曲酮。本项目中提出的纳曲酮诱导方案是基于该研究小组在过去12年中对300多名患者进行的广泛研究，证明了口服诱导策略在住院环境中的安全性和耐受性。此外，当前供资周期的试点数据表明，研究人员有能力成功地进行门诊纳曲酮诱导，导致长期保留治疗和持续戒断。寻求阿片类药物戒毒的参与者将被随机分为1)丁丙诺啡逐步诱导和逐渐减少，或2)丁丙诺啡口服纳曲酮诱导后7天，然后单次注射维维他汀。主要结果将是在第5周戒毒。次要结果将包括成功完成为期7天的戒毒程序，戒烟和参与治疗至第24周，情绪评估，以及其他药物使用结果。

DESCRIPTION (provided by applicant): Clinicians and clinical researchers engaged in opioid dependence treatment face a clear clinical imperative to improve detoxification strategies in order to avoid the pattern of early relapse and recurrent need for detoxification that characterizes present treatment efforts in this field. While agonist maintenance with methadone or buprenorphine represents the most effective strategy for ensuring long-term treatment retention, opioid replacement therapy is unacceptable to many opioid addicts, particularly those recently diagnosed or the growing proportion of prescription opioid abusers often unwilling to commit to years of opioid maintenance. Efforts to employ a gradual dose reduction of buprenorphine, in a seven- or twenty-eight-day taper, have met with very limited success to date. The addition of naltrexone, a mu opioid receptor antagonist, following buprenorphine taper represents a novel strategy for improving success of the opioid detoxification. In current clinical practice, the requirement for an inpatient detoxification in order to undergo naltrexone induction has constituted a significant barrier to opioid antagonist therapy, because of both patient unacceptability and rising insurance limitations on inpatient treatment. The investigators' extensive experience using antagonist-based treatment of opioid dependence supports the feasibility of implementing an outpatient naltrexone induction procedure. The recently available long-acting injectable formulation of naltrexone, for which FDA approval for opioid dependence is currently being sought, makes this application especially timely. Clear guidelines are needed for the effective induction onto naltrexone following the buprenorphine taper method of opioid detoxification. The proposed investigation will seek to 1) improve long-term outcomes for the buprenorphine taper method of detoxification by adding naltrexone and 2) develop a procedure using buprenorphine and low-dose naltrexone treatment initiation to permit outpatient induction onto long-acting naltrexone. The naltrexone induction regimen proposed in this project is based on previous extensive research conducted in more than 300 patients over the past 12 years by this group of investigators, demonstrating the safety and tolerability of the oral induction strategy in an inpatient setting. In addition, pilot data from the current funding cycle demonstrates the investigators' ability successfully to carry out outpatient naltrexone inductions, leading to long-term retention in treatment and sustained abstinence. Participants seeking opioid detoxification will be randomized to 1) gradual seven-day buprenorphine induction and taper or 2) seven-day buprenorphine with oral naltrexone induction followed by single Vivitrol injection. The primary outcome will be abstinence at Week 5. Secondary outcomes will include successful completion of the seven-day detoxification procedure, abstinence and engagement in treatment through Week 24, mood assessments, and other substance use outcomes.