Transcutaneous Cervical Vagal Nerve Stimulation in Patients with Posttraumatic Stress Disorder (PTSD): A Pilot Study of Effects on PTSD Symptoms and Interleukin-6 Response to Stress

Abstract

Background: Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory and sympathetic function, responsible for maintenance of symptoms. Treatment options including medications and psychotherapies have limitations. We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of this study was to assess the effects of tcVNS on PTSD symptoms and inflammatory responses to stress. Methods: Twenty patients with PTSD were randomized to double blind active tcVNS (N=9) or sham (N=11) stimulation in conjunction with exposure to personalized traumatic scripts immediately followed by active or sham tcVNS and measurement of IL-6 and other biomarkers of inflammation. Patients then self administered active or sham tcVNS twice daily for three months. PTSD symptoms were measured with the PTSD Checklist (PCL) and the Clinician Administered PTSD Scale (CAPS), clinical improvement with the Clinical Global Index (CGI) and anxiety with the Hamilton Anxiety Scale (Ham-A) at baseline and one-month intervals followed by a repeat of measurement of biomarkers with traumatic scripts. After three months patients self treated with twice daily open label active tcVNS for another three months followed by assessment with the CGI. Results: Traumatic scripts increased IL-6 in PTSD patients, an effect that was blocked by tcVNS (p<.05). Active tcVNS treatment for three months resulted in a 31% greater reduction in PTSD symptoms compared to sham treatment as measured by the PCL (p=0.013) as well as hyperarousal symptoms and somatic anxiety measured with the Ham-A p<0.05). IL-6 increased from baseline in sham but not tcVNS. Open label tcVNS resulted in improvements measured with the CGI compared to the sham treatment period p<0.05). Conclusions: These preliminary results suggest that tcVNS reduces inflammatory responses to stress, which may in part underlie beneficial effects on PTSD symptoms.

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients

“…Functional magnetic resonance imaging has shown that gammaCore specifically modulates various brain structures, including the locus coeruleus (LC) and the NTS, and that these activation patters are similar between invasive VNS, non-invasive cervical VNS, and transcutaneous auricular VNS (described further below) ( 80 – 82 ). In off-label studies, gammaCore reduced expression of interleukin [IL]-1β, IL-6, IL-8, tumor necrosis factor [TNF]), macrophage inflammatory protein [MIP]-1α, and monocyte chemoattractant protein [MCP]-1, and increased cardiac vagal tone ( 83 – 88 ). gammaCore also improved lung function in treatment-refractory emergent asthma ( 69 ).…”

“…However, less invasive neuromodulation techniques, either percutaneous or transcutaneous, may be utilized (Tables 1-4). These methods may be technically suitable for acute use, but their clinical feasibility and efficacy in COVID- (83)(84)(85)(86)(87)(88). gammaCore also improved lung function in treatment-refractory emergent asthma (69).…”

Involvement of the brain–heart axis in the link between PTSD and cardiovascular disease

“…In a single‐visit pilot study, Lamb et al (2017) found that Veterans randomized to VNS (vs. sham) demonstrated increased HRV and reduced skin conductance response to auditory startle. Using a randomized controlled/sham‐controlled design, VNS has also been shown to improve PTSD symptoms, reduce HR, improve vascular function, increase anterior cingulate and hippocampus activity, reduce limbic activity, and reduce inflammatory reactivity during a trauma script (Bremner et al, 2020, 2021; Gurel et al, 2020; Wittbrodt et al, 2020, 2021). VNS may, therefore, be a highly promising treatment for PTSD and related autonomic deficits, and new devices are currently being developed (e.g., https://www.evrenvns.com/provenresults).…”