Shiner Brian, Forehand Jenna A, Rozema Luke, Kulldorff Martin, Watts Bradley V, Trefethen Marina, Jiang Tammy, Huybrechts Krista F, Schnurr Paula P, Vincenti Matthew, Gui Jiang, Gradus Jaimie L
White River Junction Veterans Affairs Medical Center, White River Junction, Vermont; Veterans Administration National Center for PTSD, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
White River Junction Veterans Affairs Medical Center, White River Junction, Vermont.
Biol Psychiatry. 2022 Apr 1;91(7):647-657. doi: 10.1016/j.biopsych.2021.10.008. Epub 2021 Oct 20.
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.
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.
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.
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.
尽管创伤后应激障碍(PTSD)普遍存在且具有负面影响,但美国食品药品监督管理局(FDA)批准用于治疗的药物却很少,且获批药物的疗效欠佳。我们利用大规模电子健康记录数据来确定可能被重新用作PTSD治疗药物的现有药物。
我们构建了一个所有FDA批准药物的机制树,并使用基于树的扫描统计量,利用美国退伍军人事务部的电子健康记录数据,确定与PTSD症状临床上有意义的改善水平高于预期相关的药物。我们的队列包括被诊断为PTSD的患者,他们在20年期间使用PTSD检查表进行了多次症状测量(N = 168,941)。我们根据服用每种药物或与之机制相关的药物类别的患者计算观察到的数量,并根据整个树状图计算预期数量。
通常用于治疗PTSD的药物,如FDA批准的药物舍曲林,与PTSD症状的改善有关,但效果较小。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与PTSD的改善有很强的关联。该发现对于排除接受过既定PTSD治疗(包括以创伤为重点的心理治疗)同时接受肝炎治疗的患者的敏感性分析具有稳健性。
我们探索性的方法既证实了与已知PTSD药物治疗一致的发现,又发现了一类可能改善PTSD症状的新型药物。