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

患有严重精神疾病 (SMI) 共病症状的 OUD 患者服用丁丙诺啡-纳洛酮时奥氮平强化治疗：一项为期 8 周的前瞻性观察性试点研究

• 批准号: 10395719
• 负责人: ALBERT JOSEPH ARIAS
• 金额: $ 14.73万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395719
• 关键词: Adherence; Administrative Supplement; Agonist; Alcohols; Antipsychotic Agents; Behavioral; Brain imaging; Breathing; Clinic; Clinical; Cocaine; Collaborations; Cues; Data; Data Analyses; Development; Diagnosis; Disease; Disease remission; Dose; Drug usage; Electronic Health Record; Enrollment; FDA approved; Funding; Goals; Grant; Inpatients; Institutes; Laboratories; Literature; Medical; Mental disorders; Mood Disorders; National Institute of Drug Abuse; Observational Study; Odds Ratio; Opioid; Outcome; Overdose; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase II Clinical Trials; Phenotype; Pilot Projects; Pre-Clinical Model; Prospective Studies; Public Health; Research; Resources; Rodent; Schizophrenia; Self Administration; Site; Sleep; Specific qualifier value; Suboxone; Substance Use Disorder; Symptoms; Therapeutic; Time; United States; United States National Institutes of Health; Universities; Virginia; associated symptom; base; clinically relevant; cocaine use; comorbidity; data mining; early phase clinical trial; illicit opioid; imaging study; infrastructure development; innovation; medical schools; novel; olanzapine; opioid misuse; opioid overdose; opioid use; opioid use disorder; parent grant; pre-clinical; prospective; research clinical testing; response; screening; severe mental illness; week trial

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.

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个主要的公众问题。 在美国的健康问题，阿片类药物过量增加，特别是在过去的一年（1）。 需要创新的治疗方法，特别是对于患有严重精神疾病的OUD患者， 服用过量的比例要高得多（2）。最近，一种新的电子健康记录（EHR）数据挖掘方法 用于检查21年（1999年至2020年8月）收集的FDA批准的 阿片类药物使用障碍缓解期共病精神病患者的诊断 疾病，目的是确定候选药物在OUD中重复使用。研究发现， 被诊断为精神分裂症和阿片类药物使用障碍的患者中， （调整后比值比1.9）更有可能在缓解期诊断为OUD， 未开具奥氮平处方（3）。虽然相关，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） 这是一个非常具有挑战性的病人群体。从数据挖掘研究中获得灵感，NIDA治疗部门 和医学后果想要研究奥氮平在临床相关的 前瞻性研究，将在两个NIDA UG 1临床实验室内进行，位于 宾夕法尼亚医学院和弗吉尼亚联邦大学的弗吉尼亚医学院。 这些UG 1实验室的功能是筛选有前景的候选药物， 行政补充机制。鉴于文献的早期阶段，我们提出了一个两个网站，n=48 （UPenn，n=24; VCU，n=24）奥氮平在伴有严重症状的OUD患者中的观察性研究 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、MAT依从性、门诊出勤率/保留率、思维 和心境障碍症状）的变化（改善） 试验（药物诱导期后6周）。入组将在18个月内进行，之前有3- 一个月的启动/监管期，然后是3个月的数据清理、合并和分析期 在两个研究中心。