Patricia Spangler, PhD, Department of Psychiatry, Uniformed Services University, 4301 Jones Bridge Rd, Bethesda, MD 20816.
Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University, Bethesda, Maryland, USA.
J Clin Psychiatry. 2020 Oct 27;81(6):20m13233. doi: 10.4088/JCP.20m13233.
Current pharmacologic treatments for posttraumatic stress disorder (PTSD) have shown limited efficacy, prompting a call to investigate new classes of medications. The current study investigated the efficacy of glutamate modulation with riluzole augmentation for combat-related PTSD symptoms resistant to treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).
A randomized, double-blind, placebo-controlled, parallel trial was conducted at Walter Reed National Military Medical Center and Syracuse VA Medical Center between December 2013 and November 2017. Veterans and active duty service members with combat-related PTSD (per the Clinician Administered PTSD Scale [CAPS]) who were not responsive to SSRI or SNRI pharmacotherapy were randomized to 8-week augmentation with a starting dose of 100 mg/d of riluzole (n = 36) or placebo (n = 38) and assessed weekly for PTSD symptoms, anxiety, depression, disability, and side effects.
Intent-to-treat analyses (N = 74) of the primary outcome (CAPS for DSM-IV) showed no significant between-group difference in change in overall PTSD symptoms (F = 0.64, P = .422), with a small effect size (d = 0.25). There was clinically significant within-group improvement in overall PTSD symptoms in both groups, with a greater mean (SD) decrease in CAPS score in the riluzole group (-21.1 [18.9]) than in the placebo group (-16.7 [17.2]). Exploratory analyses of PTSD symptom clusters showed significantly greater improvement on hyperarousal symptoms in the riluzole group as measured by the PTSD Checklist-Specific-Subscale D (d = 0.48) and near-significant findings on the CAPS Subscale D. Riluzole augmentation was not superior to placebo on change in depression, anxiety, or disability severity.
Although preliminary, the exploratory findings of this study offer some evidence that riluzole augmentation of an SSRI or SNRI may selectively improve PTSD hyperarousal symptoms without changes in overall PTSD symptoms, depression, anxiety, or disability. Additional investigation of the mechanism of the efficacy of riluzole for hyperarousal symptoms is warranted.
ClinicalTrials.gov identifier: NCT02155829.
目前针对创伤后应激障碍（PTSD）的药物治疗效果有限，因此需要研究新的药物类别。本研究旨在探究在使用选择性 5-羟色胺再摄取抑制剂（SSRIs）或 5-羟色胺去甲肾上腺素再摄取抑制剂（SNRIs）治疗无效的情况下，使用利鲁唑增强谷氨酸能调节对与战斗相关的 PTSD 症状的疗效。
这是一项于 2013 年 12 月至 2017 年 11 月在沃尔特·里德国家军事医学中心和锡拉丘兹退伍军人事务医疗中心进行的随机、双盲、安慰剂对照、平行试验。本研究纳入了对 SSRI 或 SNRI 药物治疗无反应的与战斗相关 PTSD（根据临床医生管理 PTSD 量表[CAPS]）的退伍军人和现役军人，他们随机接受 8 周的利鲁唑起始剂量 100mg/d 的增效治疗（n=36）或安慰剂（n=38），每周评估 PTSD 症状、焦虑、抑郁、残疾和副作用。
对主要结局（DSM-IV 的 CAPS）进行意向治疗分析（N=74）显示，两组 PTSD 症状的总体变化无显著差异（F=0.64，P=0.422），效应量较小（d=0.25）。两组的 PTSD 症状均有显著的临床改善，利鲁唑组 CAPS 评分的平均（SD）降幅（-21.1[18.9]）大于安慰剂组（-16.7[17.2]）。对 PTSD 症状群的探索性分析显示，利鲁唑组在 PTSD 清单特异性子量表 D（d=0.48）上的过度唤醒症状有显著改善，CAPS 子量表 D 上的结果接近显著。与安慰剂相比，利鲁唑增效治疗在抑郁、焦虑或残疾严重程度上没有优势。
尽管初步研究，但本研究的探索性发现提供了一些证据，表明利鲁唑增强 SSRI 或 SNRIs 的疗效可能选择性地改善 PTSD 过度唤醒症状，而不改变 PTSD 症状的总体严重程度、抑郁、焦虑或残疾。需要进一步研究利鲁唑治疗过度唤醒症状的疗效机制。
ClinicalTrials.gov 标识符：NCT02155829。
