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探索真实世界证据,以发现未知的药物益处,并为抑郁和双相情感障碍的新治疗靶点的发现提供支持。

Exploring real-world evidence to uncover unknown drug benefits and support the discovery of new treatment targets for depressive and bipolar disorders.

机构信息

Janssen Research & Development, LLC., Epidemiology, Titusville, NJ, USA.

Janssen Research & Development, LLC., Epidemiology, Titusville, NJ, USA.

出版信息

J Affect Disord. 2021 Jul 1;290:324-333. doi: 10.1016/j.jad.2021.04.096. Epub 2021 May 2.

DOI:10.1016/j.jad.2021.04.096
PMID:34020207
Abstract

BACKGROUND

Major depressive and bipolar disorders are associated with impaired quality of life and high economic burden. Although progress has been made in our understanding of the underlying pathophysiology and the development of novel pharmacological treatments, a large unmet need remains for finding effective treatment options. The purpose of this study was to identify potential new mechanisms of actions or treatment targets that could inform future research and development opportunities for major depressive and bipolar disorders.

METHODS

A self-controlled cohort study was conducted to examine associations between 1933 medications and incidence of major depressive and bipolar disorders across four US insurance claims databases. Presence of incident depressive or bipolar disorders were captured for each patient prior to or after drug exposure and incident rate ratios were calculated. Medications that demonstrated ≥50% reduction in risk for both depressive and bipolar disorders within two or more databases were evaluated as potential treatment targets.

RESULTS

Eight medications met our inclusion criteria, which fell into three treatment groups: drugs used in substance use disorders; drugs that affect the cholinergic system; and drugs used for the management of cardiovascular-related conditions.

LIMITATIONS

This study was not designed to confirm a causal association nor inform current clinical practice. Instead, this research and the methods employed intended to be hypothesis generating and help uncover potential treatment pathways that could warrant further investigation.

CONCLUSIONS

Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified.

摘要

背景

重度抑郁和双相情感障碍会导致生活质量受损和经济负担加重。尽管我们在理解潜在病理生理学和开发新型药物治疗方面取得了进展,但仍有大量未满足的需求需要找到有效的治疗选择。本研究旨在确定新的潜在作用机制或治疗靶点,为未来重度抑郁和双相情感障碍的研究和开发提供信息。

方法

本研究采用自我对照队列研究,在美国四个保险理赔数据库中,研究了 1933 种药物与重度抑郁和双相情感障碍发病的关联。在药物暴露之前或之后,每位患者的抑郁或双相障碍发病情况都被记录下来,并计算发病风险比。在两个或更多数据库中,对能降低重度抑郁和双相障碍风险 50%以上的药物进行评估,将其视为潜在的治疗靶点。

结果

有 8 种药物符合纳入标准,分为三组:用于治疗物质使用障碍的药物;影响胆碱能系统的药物;以及用于治疗心血管相关疾病的药物。

局限性

本研究的目的不是为了确认因果关系,也不是为了指导当前的临床实践。相反,这项研究和所采用的方法旨在产生假说,并帮助揭示可能值得进一步研究的潜在治疗途径。

结论

本研究确定了一些可能有助于进一步研究和发现新型重度抑郁和双相情感障碍治疗方法的潜在药物靶点。

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