Mining Clinical Data for Novel Posttraumatic Stress Disorder Medications.
Mining Clinical Data for Novel Posttraumatic Stress Disorder Medications.
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DOI：
10.1016/j.biopsych.2021.10.008
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发表时间：
2022-04-01
影响因子：
10.6
通讯作者：
Gradus JL
中科院分区：
文献类型：
--
作者：
Shiner B;Forehand JA;Rozema L;Kulldorff M;Watts BV;Trefethen M;Jiang T;Huybrechts KF;Schnurr PP;Vincenti M;Gui J;Gradus JL
尽管创伤后应激障碍（PTSD）普遍存在并产生负面影响，但美国食品和药物管理局（FDA）批准用于治疗的药物很少，而且批准的药物效果不够好。我们利用大规模电子健康记录数据来识别可以重新用于治疗创伤后应激障碍（PTSD）的现有药物。我们构建了所有 FDA 批准的药物的机制树，并使用基于树的扫描统计数据，利用美国退伍军人事务部的电子健康记录数据，识别出与 PTSD 症状的临床意义改善水平高于预期水平相关的药物。我们的队列包括被诊断为 PTSD 的患者，他们在 20 年的时间里使用 PTSD 检查表重复进行症状测量 (N=168,941)。我们根据服用每种药物或机械相关类别药物的患者计算了观察到的数字，并根据整个树计算了预期数字。通常用于治疗 PTSD 的药物，例如 FDA 批准的药物舍曲林，与 PTSD 症状的改善相关，但效果很小。用于治疗丙型肝炎病毒的几种（但不是全部）直接作用抗病毒药物被证明与创伤后应激障碍（PTSD）改善有很强的相关性。这一发现对于敏感性分析来说是稳健的，排除了接受既定 PTSD 治疗的患者，包括与肝炎治疗同时进行的以创伤为中心的心理治疗。我们的探索性方法既证明了与 PTSD 药物治疗已知的结果一致的结果，又发现了一类可以改善 PTSD 症状的新型药物。
Despite the prevalence and negative impact of posttraumatic stress disorder (PTSD), there are few medications approved by the United States Food and Drug Administration (FDA) for treatment, and approved medications do not work well enough. We leveraged large-scale electronic health record data to identify existing medications that may be repurposed as PTSD treatments. We constructed a mechanistic tree of all FDA-approved medications and used the tree-based scan statistic to identify medications associated with greater than expected levels of clinically meaningful improvement in PTSD symptoms using electronic health record data from the US Department of Veterans Affairs. Our cohort included patients with a diagnosis of PTSD who had repeated symptom measurements using the PTSD Checklist over a 20-year period (N=168,941). We calculated observed numbers based on patients taking each drug or mechanistically related class of drugs and the expected numbers based on the tree as a whole. Medications typically used to treat PTSD, such as the FDA-approved agent sertraline, were associated with improvement in PTSD symptoms, but the effects were small. Several, but not all, direct-acting antivirals used in the treatment of hepatitis C virus demonstrated a strong association with PTSD improvement. The finding was robust to a sensitivity analysis excluding patients who received established PTSD treatments including trauma-focused psychotherapy concurrent with their hepatitis treatment. Our exploratory approach both demonstrated findings that are consistent with what is known about pharmacotherapy for PTSD and uncovered a novel class of medications that may improve PTSD symptoms.
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影响因子：
5.9
作者：
JACOBSON, NS;TRUAX, P
通讯作者：
TRUAX, P
影响因子：
2.6
作者：
Kulldorff, Martin;Dashevsky, Inna;Brown, Jeffrey S.
通讯作者：
Brown, Jeffrey S.
影响因子：
1.9
作者：
Kulldorff, M;Fang, ZX;Walsh, SJ
通讯作者：
Walsh, SJ
影响因子：
14.9
作者：
Bento AP;Gaulton A;Hersey A;Bellis LJ;Chambers J;Davies M;Krüger FA;Light Y;Mak L;McGlinchey S;Nowotka M;Papadatos G;Santos R;Overington JP
通讯作者：
Overington JP
影响因子：
10.6
作者：
Fonzo GA;Goodkind MS;Oathes DJ;Zaiko YV;Harvey M;Peng KK;Weiss ME;Thompson AL;Zack SE;Lindley SE;Arnow BA;Jo B;Rothbaum BO;Etkin A
通讯作者：
Etkin A