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 万美国成年患者符合重度抑郁症的标准，抑郁症的管理是医疗保健的一项主要挑战。对初始抗抑郁治疗反应不足的情况很常见，超过一半的抑郁症患者需要多个连续治疗步骤才能缓解抑郁症状。尽管疗效不大，但用第二代抗精神病药（SGA）增强抗抑郁药是治疗难治性抑郁症最有力支持和增长最快的药物治疗替代方案。每年大约有 200 万成人抑郁症门诊就诊包括 SGA。然而，在其他临床人群中发现了几种与 SGA 相关的严重不良反应，最引人注目的是老年痴呆症患者的死亡风险增加了 50% 以上，这引发了关于 SGA 治疗抑郁症的安全性的关键问题，因为目前尚不清楚 SGA 是否会产生副作用以及作用是什么。在某种程度上，这些风险普遍存在于因抑郁症而接受 SGA 增强治疗的非老年人中。不幸的是，针对抑郁症的 SGA 随机临床试验的综合经验远远不足以检测出与痴呆症中观察到的死亡风险相当的抑郁症死亡风险。因此，迫切需要观察性研究来评估 SGA 增强治疗成人抑郁症的安全性。 本研究使用最近 10 年近乎国家医疗补助数据（2001-2010 年），对大约 80,000 名患有抑郁症且对抗抑郁单药治疗反应不完全的非老年人进行了本次研究，这是第一项系统性检验 SGA 增强疗法在现实世界中的安全性的研究。拟议的推论分析将通过对抑郁症增强治疗的流行病学的严格检查（目标 1）来提供。所有推理分析都将采用主动比较器初始队列设计并使用经过验证的结果测量。我们将比较开始新一轮 SGA 增强治疗的患者和开始服用抗抑郁药物的患者之间罕见但严重的不良事件（全因死亡、心源性猝死、急性心肌梗塞、中风、2 型糖尿病、肺炎、静脉血栓栓塞）的发生率增强（目标 2a）。在此班级级别评估之后，我们将检查各个 SGA 增强策略的安全性（目标 2b）。最后，为了促进个性化治疗，我们将按年龄组和基线心血管风险检查治疗效果异质性（目标 3）。通过设计（初始队列、活跃比较组、仔细限制研究人群）和分析（使用倾向评分方法调整大量人口、临床和地理特征），可以最大限度地减少偏差。潜在的残留混杂因素将在定量敏感性分析和工具变量分析中进行检查。 结果将有助于为临床、监管和医疗保健提供信息 改善难治性抑郁症管理的政策努力，支持或驳斥大规模前瞻性安全性研究的必要性。

项目成果

Mortality risk of antipsychotic augmentation for adult depression.

成人抑郁症抗精神病药物增强的死亡风险。

• 发表时间: 2020
• 影响因子: 3.7
• 作者: Gerhard, Tobias;Stroup, T Scott;Correll, Christoph U;Setoguchi, Soko;Strom, Brian L;Huang, Cecilia;Tan, Zhiqiang;Crystal, Stephen;Olfson, Mark
• 通讯作者: Olfson, Mark

Antipsychotic Medication Treatment Patterns in Adult Depression.

成人抑郁症的抗精神病药物治疗模式。

• 发表时间: 2018
• 作者: Gerhard, Tobias;Stroup, T Scott;Correll, Christoph U;Huang, Cecilia;Tan, Zhiqiang;Crystal, Stephen;Olfson, Mark
• 通讯作者: Olfson, Mark