Cervical non-invasive Vagus Nerve Stimulation (nVNS) presents a promising avenue for managing anxiety and depression in individuals unresponsive to traditional treatments. This study evaluates the efficacy and user experience of nVNS therapy in a 30-day trial with 34 participants experiencing stress-related issues. Results indicate significant improvements in mood and well-being over the trial period, with notable increases in reported happiness and overall wellness. Moreover, the majority expressed interest in continuing treatment beyond the trial, suggesting potential long-term benefits. No adverse events were reported. These findings highlight the potential of non-invasive vagus nerve stimulation as a therapeutic option for mood disorders, warranting further research to confirm and explore its full scope.

• nVNS
• Vagus Nerve Stimulation
• Mood Improvement
• Sleep

Grillot JM, Staats PS (2025) An Open-Label Trial of Cervical Non-Invasive Vagus Nerve Stimulation Using a Proprietary Signal for the Man- agement of Sleep and Depressed Mood. JSM Anxiety Depress 6(1): 1029.

Non-invasive Vagus Nerve Stimulation (nVNS) has emerged as a promising therapeutic strategy for managing anxiety and depression, particularly for individuals who have not responded to conventional pharmacological or psychotherapeutic treatments [1,2]. Unlike invasive methods involving implanted devices, nVNS delivers electrical pulses to the vagus nerve transcutaneously, without the need for surgical intervention. These pulses are transmitted to key cortical regions involved in mood regulation, such as the limbic system and prefrontal cortex [3].

By modulating neural activity in these areas, nVNS has demonstrated efficacy in alleviating symptoms of depression and anxiety. The exact mechanisms underlying its therapeutic effects are still being elucidated, but both preclinical and clinical research suggest several potential pathways. nVNS may enhance neuroplasticity, facilitate the release of mood-regulating neurotransmitters including serotonin and norepinephrine, and modulate the activity of neurotransmitter systems crucial for mood regulation [1]. Due to the relationship between inflammatory activation and anxiety, there is reason to suggest that nVNS may be a promising therapy for stress reduction. Non-invasive vagus nerve stimulation has been shown to reduce both central and peripheral inflammatory markers associated with anxiety and depression, such as IL-6.

Moreover, nVNS is believed to influence the autonomic nervous system, promoting a shift from sympathetic dominance, which is associated with stress and anxiety, to parasympathetic dominance, associated with relaxation and well-being [1,4]. This multifaceted approach holds promise for restoring balance to dysregulated neural circuits implicated in mood disorders. Given the robust mechanism of action, cervical VNS has been studied in a range of disorders including opioid addiction, PTSD, primary headache disorders, Parkinson’s, epilepsy, and stroke [5-10].

There have been several studies demonstrating efficacy of an implanted vagus nerve stimulator on mood and depression [11]. However, surgical implantation is associated with risks from paralysis of the vocal cords to hoarseness. Transcutaneous auricular vagus nerve stimulators have been demonstrated to improve mood after effort exertion, but only access less than one percent of the vagal fibers and require 90 minutes of stimulation [12,13]. Given the number of patients with anxiety and difficulty sleeping, having a non-surgical, non-drug, treatment that activates the vagus nerve non-invasively in a two-minute session would be valuable. A non-invasive vagus nerve stimulator wellness device using this proprietary signal has become available (Truvaga.com). There have been no reports of serious complications, such as bradycardia or hoarseness with this device.

Overall, non-invasive cervical vagus nerve stimulation represents an exciting and potentially effective treatment option for individuals grappling with the debilitating effects of poor sleep and depressed mood. Its non-invasive nature and promising therapeutic outcomes offer hope for those who have not found relief through traditional interventions.

On January 13 2023, 34 subjects who must feel stressed when coming in to the study, were enrolled in an open label trial of a cervical non-invasive vagus nerve stimulator using a patented proprietary signal (Truvaga electroCore Basking Ridge NJ) twice daily (one 2-minute session morning and night) for 30 days. 34 participants (85%) met the inclusion and compliance criteria and were asked to evaluate the efficacy of treatment and overall experience on day 7 and day 30 of the study. All participants self-reported that they are currently seeking to enhance their overall wellness, experience moderate to severe stress and sleep-related issues, and have moderate to severe difficulties focusing on daily tasks. Additionally, participants must be parents with at least one child under 18 living in the home. Participants were allowed to maintain their current regimen of stress, sleep and/or anxiety over the counter and prescription medications during the testing period.

However, they were instructed not to introduce any new over the counter or prescription medications or therapies for the duration of the test. Participants who work in, or have a household member employed in cosmetics, skincare, medical device, or pharmaceutical industries were excluded from the study. Additionally, individuals who are pregnant, lactating, or intended to become pregnant within 12 weeks, as well as those with implantable medical devices like pacemakers or hearing aids, were not eligible. Presence of metallic devices near or implanted in the neck, or recent participation in a testing panel within the past 6 months, also disqualified potential participants from the study.

Self-reported  questionnaire  results  demonstrated that participants had an overall positive experience with cervical nVNS using a proprietary signal (electroCore Rockaway NJ) in terms of efficacy across multiple domains. Patient experience continued to improve over the 30-day trial period (Figure 1,2).

Figure 1: Percentage of patients reporting improvement on a variety of domains following use of cervical non-invasive vagus nerve stimulation at one week and at thirty days of use.

Figure 2: At the conclusion of the study, subjects were asked on a scale from 1 to 10, how effective was the therapy at improving the following symptoms: focus, energy, mood, anxiety, sleep, and stress?

The use of bioelectric medicine has recently received increased attention in multiple medical and lifestyle domains. Vagus nerve stimulation has recently been used in disorders from headaches to rheumatologic disorders with promising results. It is important to understand the broad benefits of vagus nerve stimulation across multiple domains. The various strategies that have been employed for stimulating the vagus nerve do not all activate the vagus nerve equally. Although auricular stimulation provides easy access to a very small branch of the vagus nerve, it carries less than one percent of vagal fibers. The signal used by the interventional device is a proprietary 5000 hertz sine wave that bursts at a rate of 25 hertz. This signal has been demonstrated in multiple studies to safely activate the vagus nerve in the neck. Other signals that have not been fully tested may not provide the same level of safety or efficacy.

In conclusion, the findings of this open-label trial of cervical non-invasive vagus nerve stimulation using a proprietary signal had a broad range of wellness benefits. Through a 30-day In-Home Use Test (IHUT) involving 34 participants, the efficacy and overall experience of noninvasive cervical vagus nerve stimulation were evaluated. By day 30 subjects experienced a 62-94% improvement in a variety of domains listed above.

Results indicate a significant improvement in the domains related to mood and well-being over the course of the trial. There appears to be a significant improvement from day one to day seven, and a subsequent significant improvement day 7 to day 30 of the trial. Furthermore, most participants expressed a desire to continue treatment with cervical nVNS therapy beyond the trial period, highlighting the potential long-term benefits of noninvasive cervical vagus nerve stimulation for managing sleep and anxiety [14-18]. One limitation of this study is that it does not include a sham control group. The potential biases in this single-arm study can be mitigated in future work by adding a sham group with which to compare and further isolate the effects of nVNS. Similar studies have found it difficult to identify a sham device that is not only safe for participants but ethically sound, as these devices will elicit no benefit but may cause harm [18]. In future studies, the inclusion of a sham control group may add validity to the benefits of nVNS demonstrated in this study.

No adverse events were reported during the 30- day study period. This same frequency has been used commercially for headaches in Europe and in the United States since 2011 and 2017 respectively. The device has an excellent safety profile and has not been shown to have any cardiac effects. These findings underscore the promising nature of noninvasive vagus nerve stimulation as a therapeutic approach for individuals seeking relief from the debilitating effects of anxiety and depression. Further research and larger-scale studies are warranted to confirm these initial findings and explore the full potential of cervical vagus nerve stimulation in improving overall well-being and quality of life for individuals with mood disorders.

Dr. Staats is a founder and Chief Medical officer of electroCore, and Chairman of the Vagus Nerve Society, Ms. Salek is an employee of electroCore.

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