Safety of Second Generation Antipsychotics for Adult Depression

第二代抗精神病药治疗成人抑郁症的安全性

• 批准号: 8875778
• 负责人: Tobias Gerhard
• 金额: $ 19.38万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8875778
• 关键词: Acute myocardial infarction; Address; Adjuvant; Adult; Adverse effects; Affect; Age; American; Antidepressive Agents; Antipsychotic Agents; Area; Cardiovascular Diseases; Cessation of life; Characteristics; Clinical; Data; Data Files; Dementia; Diagnosis; Disease remission; Dose; Economics; Elderly; Emotional; Epidemiology; FDA approved; Generations; Health; Health Policy; Healthcare; Heterogeneity; Incidence; Individual; Major Depressive Disorder; Medicaid; Mental Depression; Non-Insulin-Dependent Diabetes Mellitus; Observational Study; Office Visits; Outcome Measure; Outpatients; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacological Treatment; Physicians; Pneumonia; Population; Population Study; Premature Mortality; Prevalence; Public Health; Randomized Clinical Trials; Randomized Controlled Trials; Registries; Residual state; Resources; Risk; Safety; Sample Size; Scoring Method; Sequential Treatment; Serious Adverse Event; Severities; Severity of illness; Stroke; Subgroup; Thromboembolism; Treatment Step; Venous; Visit; active comparator; age group; alternative treatment; base; cardiovascular risk factor; cohort; comparative; depressed patient; depressive symptoms; design; experience; falls; follow-up; improved; inclusion criteria; indexing; instrument; meetings; mortality; non-psychotic depression; older patient; personalized medicine; preference; prospective; psychotic depression; response; safety study; sudden cardiac death; treatment effect; treatment-resistant depression

DESCRIPTION (provided by applicant): With more than 15 million adult Americans meeting criteria for major depressive disorder each year, the management of depression is a central health care challenge. Inadequate response to initial antidepressant treatment is common and more than half of depressed patients require multiple sequential treatment steps to achieve remission of depressive symptoms. Despite modest efficacy, augmentation of antidepressants with second-generation antipsychotics (SGAs) is the most strongly supported and fastest growing pharmacological treatment alternative for treatment-resistant depression. Each year approximately 2 million outpatient visits for adult depression include a SGA. Yet the discovery of several serious SGA-associated adverse effects in other clinical populations, most strikingly a >50% increase in mortality risk in elderly dementia patients, raises critical questions about the safety of SGAs in depression as it is not known whether and to what extent these risks generalize to non-elderly adults who receive SGA augmentation for depression. Unfortunately, the combined experience of randomized clinical trials of SGAs for depression falls far short of sufficient power to detect a mortality risk in depression comparable to that observed in dementia. As a result, there is an urgent need for observational research to assess the safety of SGA augmentation in the treatment of adult depression. Using the most recent available 10 years of near national Medicaid data (2001-2010), the present study in approximately 80,000 non-elderly adults with depression and incomplete response to antidepressant monotherapy is the first to systematically examine the real-world safety of SGA augmentation. The proposed inferential analyses will be informed by a rigorous examination of the epidemiology of augmentation treatments in depression (Aim 1). All inferential analyses will employ an active comparator inception cohort design and use validated outcome measures. We will compare the incidence of rare, but serious, adverse events (all-cause mortality, sudden cardiac death, acute myocardial infarction, stroke, type 2 diabetes, pneumonia, venous thromboembolism) between patients initiating new episodes of SGA augmentation and those initiating antidepressant augmentation (Aim 2a). Following this class-level assessment, we will examine the safety of individual SGA augmentation strategies (Aim 2b). Finally, to facilitate personalized treatment, we will examine treatment effect heterogeneity by age group and baseline cardiovascular risk (Aim 3). Bias will be minimized by design (inception cohort, active comparator groups, careful restriction of the study population) and in the analysis (adjustment for a large number of demographic, clinical, and geographic characteristics using propensity score methods). Potential residual confounding will be examined in quantitative sensitivity analysis and instrumental variable analysis. The results will help inform clinical, regulatory, and health care policy efforts to improve the management of treatment-resistant depression and support or refute the need for large-scale prospective safety studies.

描述（由申请人提供）：每年有超过1500万的成年美国人符合重度抑郁症的标准，抑郁症的管理是一个中央医疗保健挑战。对初始抗抑郁药治疗的反应不足是常见的，超过一半的抑郁症患者需要多个顺序治疗步骤以缓解抑郁症状。尽管有适度的功效，但第二代抗精神病药（SGA）的抗抑郁药增强是最受支持，增长最快的药理学治疗方法，可用于治疗耐药性抑郁症。每年大约有200万个成人抑郁症的门诊就诊包括SGA。然而，在其他临床人群中发现了几种严重的SGA相关的不良反应，最令人惊讶的是，老年痴呆症患者的死亡风险增加了50％，对SGA在抑郁症中的安全性提出了关键的问题，因为尚不知道这些风险是否以及这些风险在何种程度上概括为抑郁症的非老年人。不幸的是，SGA抑郁症的随机临床试验的综合经验远远没有足够的能力来检测可与痴呆症中观察到的抑郁症的死亡率风险相当。结果，迫切需要观察性研究来评估SGA增强在治疗成人抑郁症中的安全性。 使用最新的10年近国家医疗补助数据（2001-2010），目前对大约80,000名非抑郁症的非较大成年人的研究，对抗抑郁药单药治疗的反应不完全，是第一个系统地检查SGA增强的现实安全性。拟议的推论分析将通过对抑郁症增强治疗的流行病学进行严格的检查来告知（AIM 1）。所有推论分析将采用主动比较人群组合设计并使用经过验证的结果指标。我们将比较罕见但严重的不良事件（全因死亡率，突然死亡率，急性心肌梗塞，中风，2型糖尿病，肺炎，肺炎，静脉血栓栓塞）的发生率之间发起了新的SGA增强事件和发起抗抑郁药增强的新事件（AIG 2A）。在此类级别的评估之后，我们将研究单个SGA增强策略的安全性（AIM 2B）。最后，为了促进个性化治疗，我们将根据年龄组和基线心血管风险检查治疗效应异质性（AIM 3）。偏见将通过设计（成立队列，主动比较组，仔细限制研究人群）和分析（使用倾向分数方法调整大量人口统计学，临床和地理特征）。潜在的残留混淆将在定量灵敏度分析和仪器变量分析中检查。 结果将有助于告知临床，监管和医疗保健 改善对治疗抑郁症的管理的政策努力，并支持或驳斥对大规模前瞻性安全研究的需求。

项目成果

Mortality risk of antipsychotic augmentation for adult depression.

• DOI: 10.1371/journal.pone.0239206
• 发表时间: 2020
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gerhard T;Stroup TS;Correll CU;Setoguchi S;Strom BL;Huang C;Tan Z;Crystal S;Olfson M
• 通讯作者: Olfson M