Powers Mark B, Hays Seth A, Rosenfield David, Porter Amy L, Gallaway Holle, Chauvette Greg, Smits Jasper A J, Warren Anne Marie, Douglas Megan, Naftalis Richard, Wigginton Jane G, Foreman M, Kilgard Michael P, Rennaker Robert L
Baylor Scott & White Research Institute, Dallas, TX 75246, USA.
Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science, University of Texas at Dallas, Richardson, TX 75080, USA; Texas Biomedical Device Center, University of Texas at Dallas, Richardson, TX 75080, USA.
Brain Stimul. 2025 May-Jun;18(3):665-675. doi: 10.1016/j.brs.2025.03.007. Epub 2025 Mar 15.
Posttraumatic stress disorder (PTSD) is common and debilitating, and many individuals do not respond to existing therapies. We developed a fundamentally novel neuromodulation-based therapy for treatment-resistant PTSD. This approach is premised on coupling prolonged exposure therapy, a first-line evidence-based cognitive behavioral therapy that directs changes within fear networks, with concurrent delivery of short bursts of vagus nerve stimulation (VNS), which enhance synaptic plasticity.
We performed a first-in-human prospective open-label early feasibility study (EFS) using a next-generation miniaturized system to deliver VNS therapy in nine individuals with moderate to severe treatment-resistant PTSD. All individuals received a standard 12-session course of prolonged exposure therapy combined with VNS. Assessments were performed before, 1 week after, and 1, 3, and 6 months after the completion of therapy.
gov registration: NCT04064762.
VNS therapy resulted in significant, clinically-meaningful improvements in multiple metrics of PTSD symptoms and severity compared to baseline (CAPS-5, PCL-5, and HADS all p < 0.001 after therapy). These benefits persisted at 6 months after the cessation of therapy, suggesting lasting improvements. All participants showed loss of PTSD diagnosis after completing treatment. No serious or unexpected device-related adverse events were observed.
These findings provide a demonstration of the safety and feasibility of VNS therapy for PTSD and highlight the potential of this approach. Collectively, these support the validation of VNS therapy for PTSD in a rigorous randomized controlled trial.
创伤后应激障碍（PTSD）很常见且使人衰弱，许多患者对现有治疗方法无反应。我们开发了一种全新的基于神经调节的疗法来治疗难治性PTSD。这种方法的前提是将延长暴露疗法（一种基于证据的一线认知行为疗法，可引导恐惧网络发生变化）与同时进行的短脉冲迷走神经刺激（VNS）相结合，后者可增强突触可塑性。
我们进行了一项首次人体前瞻性开放标签早期可行性研究（EFS），使用下一代小型系统为9名中度至重度难治性PTSD患者提供VNS治疗。所有患者均接受了标准的12节延长暴露疗法课程并结合VNS。在治疗前、治疗后1周以及治疗完成后1、3和6个月进行评估。
美国国立医学图书馆临床试验注册库登记号：NCT04064762。
与基线相比，VNS治疗在PTSD症状和严重程度的多个指标上产生了显著的、具有临床意义的改善（治疗后CAPS-5、PCL-5和HADS的p值均<0.001）。这些益处治疗停止后6个月仍持续存在，表明有持久的改善。所有参与者在完成治疗后均不再被诊断为PTSD。未观察到严重或意外的与设备相关的不良事件。
这些发现证明了VNS治疗PTSD的安全性和可行性，并突出了这种方法的潜力。总体而言，这些结果支持在严格的随机对照试验中验证VNS治疗PTSD的有效性。
