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Mining Clinical Data for Novel Posttraumatic Stress Disorder Medications
Biological Psychiatry ( IF 9.6 ) Pub Date : 2021-10-20 , DOI: 10.1016/j.biopsych.2021.10.008
Brian Shiner 1 , Jenna A Forehand 2 , Luke Rozema 2 , Martin Kulldorff 3 , Bradley V Watts 4 , Marina Trefethen 2 , Tammy Jiang 5 , Krista F Huybrechts 6 , Paula P Schnurr 7 , Matthew Vincenti 4 , Jiang Gui 8 , Jaimie L Gradus 5
Affiliation  

Background

Despite the prevalence and negative impact of posttraumatic stress disorder (PTSD), there are few medications approved by the U.S. Food and Drug Administration 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.

Methods

We constructed a mechanistic tree of all Food and Drug Administration–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 U.S. 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.

Results

Medications typically used to treat PTSD, such as the Food and Drug Administration–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 hepatitis treatment.

Conclusions

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.



中文翻译:

挖掘新型创伤后应激障碍药物的临床数据

背景

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批准用于治疗的药物很少,而且批准的药物效果不佳。我们利用大规模电子健康记录数据来识别可重新用作 PTSD 治疗的现有药物。

方法

我们构建了所有食品和药物管理局批准的药物的机制树,并使用基于树的扫描统计数据使用来自美国退伍军人事务部的电子健康记录数据来识别与 PTSD 症状的临床有意义改善高于预期水平相关的药物. 我们的队列包括诊断为 PTSD 的患者,他们在 20 年期间使用 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药物类别的患者计算观察到的数量,并根据整个树计算预期数量。

结果

通常用于治疗 PTSD 的药物,例如食品和药物管理局批准的药物舍曲林,与 PTSD 症状的改善有关,但效果很小。几种(但不是全部)用于治疗丙型肝炎病毒的直接作用抗病毒药物证明与 PTSD 改善密切相关。这一发现对于排除接受既定 PTSD 治疗(包括以创伤为中心的心理治疗,同时接受肝炎治疗)的患者的敏感性分析是稳健的。

结论

我们的探索性方法既证明了与已知的 PTSD 药物疗法一致的发现,又发现了一类可以改善 PTSD 症状的新型药物。

更新日期:2021-10-20
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