PRIME Care (PRecision medicine In MEntal health Care)

背景：在过去的几年里，商业药物遗传学（PGx）测试精神病 药物作为实施“精准医疗”的一种手段已经变得普遍，一些保险公司 选择支付测试费用。这些事态发展给退伍军人带来了越来越大的压力 健康管理局实施一个以心理健康为重点的PGxs计划，特别是治疗抑郁症， 但是没有足够的科学研究来支持临床应用的效用。 目的：我们提出了一个研究计划，以评估PGx检测在治疗主要 抑郁症 方法：多中心、随机临床试验（n=2000）。患者/提供者配对将被随机分配至 随机化后立即（即干预组）或6个月后接受PGx电池检查结果 常规治疗（即延迟结果组）。本研究将检验以下假设： 1.患有MDD的退伍军人，其护理由PGx电池的结果指导， 通过患者健康问卷-9测量， （PHQ-9）评分<5。 2.接收PGx组合的结果的提供者/患者对（即，干预组）将使用 在延迟结果组中，试验禁忌的药物比二对儿少。 将使用以下受试者入选和排除标准： 入选标准。a）年龄18至80岁，包括18岁和80岁; B）PHQ-9评分>10和推定诊断 根据PHQ 9标准，MDD的风险; c）至少一次MDD既往治疗暴露（心理治疗或 抗抑郁药）; d）打算开始用抗抑郁药治疗MDD，以及e）愿意提供 签署了参与研究的知情同意书。 排除标准。a）目前严重的合并精神疾病（即，双相精神分裂症 障碍、精神病性重性抑郁症、边缘性或反社会人格障碍、进食障碍; B）当前 DSM-5诊断为中度或重度酒精使用障碍; c）当前DSM-5诊断为药物使用障碍 （尼古丁或大麻除外）; d）PTSD检查表（PCL-5）评分> 39; e）目前使用抗精神病药物 药物; f）增强治疗，例如，当时一种或多种抗抑郁药的现有处方 随机化，不包括本研究处方的索引抗抑郁药;剂量为 低于150 mg/天将不被认为是增加;和f）住院治疗时， 同意. 对退伍军人医疗保健的预期影响：尽管有如此紧迫的流行病学需要， 抑郁症的治疗往往是不够的。正如现在的几项研究所显示的，要从 对于抑郁症，患者和提供者必须坚持不懈，尝试多种治疗方法，直到他们找到一种两者兼而有之的治疗方法。 宽容和有效。然而，每一轮治疗，都有更大的治疗损耗。 复制迄今为止进行的有限PGx实施研究的结果， 开创了MDD治疗的新时代，并为早期诊断和治疗提供了动力， 更快更高的缓解率。

Background: In the last several years, commercial pharmacogenetic (PGx) testing for psychotropic medications has become widespread as a means of implementing “precision medicine”, with some insurers electing to cover the cost of testing. These developments have put increasing pressure on the Veterans Health Administration to implement a mental health focused PGxs program, especially for treating depression, but without sufficient scientific study to support the utility of clinical application. Objectives: We propose a program of research to evaluate the utility of PGx testing in treating Major Depressive Disorder. Methods: Multi-site, randomized clinical trial (n=2000). Patient/provider dyads will be randomly assigned to receive the results of PGx battery either right after randomization (i.e. intervention group) or after 6 months of treatment as usual (i.e. delayed results group). The study will test the following hypotheses: 1. Veterans with MDD whose care is guided by the results of the PGx battery will have a higher rate of remission than those in the delayed results group, as measured by a Patient Health Questionnaire–9 (PHQ-9) score <5. 2. Provider/patient dyads that receive the results of the PGx battery (i.e., the intervention group) will use fewer medications contraindicated by the testing than dyads in the delayed results group. The following subject inclusion and exclusion criteria will be used: Inclusion Criteria. a) age 18 to 80 years, inclusive; b) PHQ-9 score of >10 and a presumptive diagnosis of MDD per PHQ9 criteria; c) at least one prior treatment exposure for MDD (psychotherapy or antidepressant); d) intent to start treatment of the MDD with an antidepressant, and e) willing to provide signed, informed consent to participate in the study. Exclusion Criteria. a) current serious co-occurring psychiatric illness (i.e., schizophrenia, bipolar disorder, psychotic major depression, borderline or antisocial personality disorder, eating disorder; b) current DSM-5 diagnosis of moderate or severe alcohol use disorder; c) current DSM-5 diagnosis of drug use disorder (other than nicotine or cannabis); d) PTSD checklist (PCL-5) score > 39; e) current use of an antipsychotic medication; f) augmentation therapy, e.g., an existing prescription of one or more antidepressants at the time of randomization, exclusive of the index antidepressant prescribed for the current study; trazadone at a dosage of less than 150 mg/day will not be considered augmentation; and f) inpatient hospitalization at the time of consent. Anticipated Impact on Veteran's Healthcare: Despite such a compelling epidemiological imperative, the treatment of depression is often inadequate. As shown now in several studies, to achieve remission from depression, patients and providers must be persistent and try multiple treatments until they find one that is both tolerable and effective. However, with each round of treatment, there is greater attrition from treatment. Replication of the results from the limited PGx implementation studies that have been conducted to date could usher in a new era in the treatment of MDD and provide an impetus for early diagnosis and treatment, resulting in more rapid and higher rates of remission.