Olanzapine Augmentation in OUD Patients on Buprenorphine-Naloxone with Comorbid Symptoms of Serious Mental Illness (SMI): A Prospective Observational 8-week Pilot Study

尽管FDA批准了阿片类药物使用障碍(OUD)的治疗方法，但阿片类药物滥用仍然是一种主要的公共疾病 美国的健康问题，阿片类药物过量增加，特别是在过去一年(1)。 需要创新的治疗方法，特别是对患有严重精神疾病的OUD患者，其 过量服药率高得多(2)。最近，一种新的电子健康记录数据挖掘方法 用于检查21年(1999-2020年8月)收集的FDA批准的协会的数据 共病精神病患者缓解期阿片类药物使用障碍的诊断 疾病，目的是确定在OUD重复使用的候选药物。研究发现，患者 被诊断为精神分裂症和阿片类药物使用障碍的人服用奥氮平的次数接近两次 (调整后的优势比1.9)与以下患者相比，更有可能被诊断为OUD正在缓解 未开奥氮平(3)。尽管相关，但这一发现表明奥氮平可能是一种 阿片类药物使用障碍和严重共病症状患者的有效抗精神病药物治疗 精神疾病(SMI)。如果有益，奥氮平可以帮助降低(否则会升高的)过量服药率。 这是一群极具挑战性的患者。从NIDA治疗部门的数据挖掘研究中获得灵感 和医学后果想要调查奥氮平在临床相关的潜在益处 前瞻性研究，将在位于华盛顿大学的两个NIDA UG1临床实验室内进行 宾夕法尼亚医学院和弗吉尼亚联邦大学弗吉尼亚医学院。 这些UG1实验室的功能是筛选具有临床益处的有前景的候选药物，使用 行政补充机制。考虑到文献的早期阶段，我们建议两个站点，n=48 加州大学宾夕法尼亚分校(UPenn，n=24)奥氮平治疗重症心绞痛患者的观察研究 精神疾病(SMI)，服用稳定剂量的丁丙诺啡-纳洛酮至少两周。指定的 结果(例如，非法阿片类药物使用、其他药物使用、睡眠、垫子依从性、门诊就诊/保留、思想 和情绪障碍症状)的奥氮平将检查变化(改善)在8周 试验(用药诱导期后6周)。注册将在18个月内进行，之前将进行3- 一个月的启动/调节期，然后是3个月的清理、合并和分析数据的时间 在这两个研究地点。

Despite FDA-approved treatments for opioid use disorder (OUD), opioid misuse continues to be a major public health problem in the United States, with opioid overdoses increasing especially over the last year (1). Innovative treatments are needed, especially for OUD patients with comorbid serious mental illness, whose overdose rates are much higher (2). Recently, a novel electronic health record (EHR) data-mining approach was used to examine data collected across 21 years (1999-August 2020) on the associations of FDA-approved medications with the diagnosis of Opioid Use Disorder in Remission among patients with comorbid psychiatric illness, with the goal of identifying candidate medications for re-use in OUD. The study found that patients diagnosed with schizophrenia and Opioid Use Disorder who were prescribed olanzapine were nearly two times (Adjusted Odds Ratio 1.9) more likely to have a diagnosis of OUD in Remission, as compared to patients who were not prescribed olanzapine (3). Though correlational, this finding suggested that olanzapine may be a helpful antipsychotic medication for patients with opioid use disorder and symptoms of comorbid serious mental illness (SMI). If beneficial, olanzapine could help reduce the (otherwise-elevated) rate of overdose in this very challenging patient group. Taking inspiration from the data-mining study, NIDA Division of Therapeutic and Medical Consequences would like to investigate the potential benefit of olanzapine in a clinically relevant prospective study, to be conducted within the two NIDA UG1 Clinical Laboratories, located at the University of Pennsylvania School of Medicine and at the Medical College of Virginia at Virginia Commonwealth University. The function of these UG1 laboratories is to screen promising candidate medications for clinical benefit, using the Administrative Supplement mechanism. Given the early stage of the literature, we propose a two-site, n=48 (UPenn, n=24; VCU, n=24) observational study of olanzapine in OUD patients with symptoms of serious mental illness (SMI), on a stable dose of buprenorphine-naloxone for at least two weeks. The specified outcomes (e.g., illicit opioid use, other drug use, sleep, MAT adherence, clinic attendance/retention, thought and mood disorder symptoms) on olanzapine will be examined for change (improvement) across the 8-week trial (6 weeks after medication induction phase). Enrollment will occur across 18 months, preceded by a 3- month start-up/regulatory period, and followed by a 3-month period for cleaning, combining and analyzing data across the two study sites.