tVNS® E is currently the only transcutaneous, non-invasive vagus nerve stimulation device approved in Europe under the new Medical Device Regulation (MDR EU 2017/745). tVNS® E is explicitly approved for the indications epilepsy, chronic migraine, depression, and Prader-Willi syndrome.
Reduction in seizure frequency over a 28-day period during the intervention compared with the phase before the intervention by at least 25% after 20 weeks of treatment.
Reduction of the depression-specific HAMD score by at least 2 to 3 points in adult patients when used alongside psycho-pharmacological and psycho-therapeutic treatments after 9 weeks of treatment.
Reduction in the frequency of migraine days by 50% after 12 weeks of treatment.
Reduction in the average number of outbursts per day compared with the average number of outbursts per day in a phase before the intervention by at least 50% after 12 months of treatment.
The tVNS® E is the first and currently the only medical device of its kind on the market that is certified in accordance with the current European Medical Devices Regulation 2017/745 (MDR) and is authorised for the treatment of treatment-resistant depression and epilepsy, chronic migraine and Prader-Willi syndrome in patients aged 18 and over. It is certified as Safety Class IIa and is therefore in the same category as hearing aids, for example. Transcutaneous, auricular vagus nerve stimulation with the tVNS E is a systemic therapy, as it targets the afferent branch of the vagus nerve in the cymba conchae. The vagus nerve is one of the so-called cranial nerves. Unlike the spinal nerves, the twelve cranial nerves originate directly from the brain. From there, they extend to a wide variety of points in the head and neck region or, as in the case of the vagus nerve, even as far as the trunk. Put simply, the vagus nerve is the link between our brain and our internal organs. The vagus nerve is the part of the nervous system responsible for relaxation, calm and recovery. It has been known for many years that electrical stimulation of the vagus nerve is associated with positive effects in many clinical conditions. Numerous research projects are currently underway, and the device is being used ‘off-label’ in conditions such as Parkinson’s disease, atrial fibrillation, anxiety disorders, ME/CFS, chronic inflammatory bowel disease, atrial fibrillation, cognitive impairments, systemic sclerosis, sleep disorders, stroke and tinnitus.
A randomized, double-blind crossover study of 20 seizure-free temporal lobe epilepsy patients found that 4 hours of transcutaneous vagus nerve stimulation (tVNS) dampened the natural cortisol decline and reduced salivary flow rate compared to sham stimulation. This suggests modest short-term effects on stress-related biological systems, though subjective stress and tiredness were unchanged.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A 30-subject EEG study found that transcutaneous auricular vagus nerve stimulation (taVNS) modifies functional brain network properties in ways that differ by epilepsy type. Generalized and focal epilepsy groups showed opposite patterns of network reorganization during and after stimulation, suggesting taVNS effects are not uniform across epilepsy types. Local brain network changes were largely diffuse and non-specific.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A crossover study of 15 patients with drug-resistant epilepsy found that neither acute invasive VNS nor taVNS improved verbal memory performance on a word recognition task. However, memory scores improved significantly after 6 weeks of VNS treatment, suggesting sustained, repetitive stimulation at moderate intensity is needed to meaningfully enhance memory function.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A prospective trial of 14 epilepsy patients found that one hour of taVNS produced measurable, often persistent changes in EEG-derived brain network properties, including increased integration, robustness, and stability. Importantly, these network modifications occurred without any negative impact on cognition or behavior, suggesting taVNS may promote a more resilient epileptic brain network.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A multicenter feasibility trial of taVNS in 37 drug-resistant epilepsy patients was terminated early due to poor recruitment and high dropout. Only 59% completed six months and 16% completed the full 18-month follow-up. The findings highlight that patient adherence and device usability are critical barriers to real-world taVNS adoption, independent of clinical efficacy.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A comprehensive review of 30 years of VNS literature found that invasive VNS achieves 50% seizure reduction in roughly 45 to 65% of drug-resistant epilepsy patients, with efficacy peaking around 6 months and continuing to improve for up to 2 years. Non-invasive taVNS shows promise but remains limited by small study sizes, inconsistent protocols, and lack of long-term data.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A retrospective study of 52 post-stroke epilepsy patients found that 4 weeks of taVNS showed no significant improvement in seizure frequency, seizure duration, or quality of life compared to a waiting-list control group. The authors attributed the null findings to a short treatment duration, low stimulation dose, and small sample size.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A double-blind RCT of 76 drug-resistant epilepsy patients comparing 25 Hz taVNS against 1 Hz active control found no statistically significant superiority for the active treatment group overall. However, patients who completed the full 20-week treatment showed a significant 34% seizure reduction, and adherence was high. The authors concluded that larger, longer trials are warranted.
After a 20 week treatment period, active tVNS® patients recorded an average 34.2% reduction of seizure frequency.
A case report of a 17-year-old with longstanding treatment-resistant depression found that 7.5 months of daily home-based taVNS, adjunct to escitalopram, was feasible and well-tolerated, with modest improvements in self-reported and clinician-rated depression scores. The authors note that existing protocols are not yet optimized for adolescents and call for dedicated pediatric research.
tVNS® led to a reduction of depression-specific HAMD score of a minimum of 2-3 points in adult patients when used in parallel with psychopharmacological and psychotherapy treatments after a period of 9 weeks.
A crossover study of 30 MDD patients and 29 healthy controls found that taVNS boosted effort invigoration during the first session in both groups, with gains persisting into a second session rather than requiring repeated acute stimulation. Patients with MDD showed trial-by-trial increases in both invigoration and reward wanting during taVNS, suggesting the stimulation may facilitate motivational learning that could complement existing depression treatments.
tVNS® led to a reduction of depression-specific HAMD score of a minimum of 2-3 points in adult patients when used in parallel with psychopharmacological and psychotherapy treatments after a period of 9 weeks.
A single-arm feasibility study of 20 treatment-resistant depression patients found that 80% achieved the compliance threshold of 4 hours of daily taVNS over 4 weeks. Side effects were mild and mostly local. Significant reductions in depression severity and improvements in cognitive speed were observed, supporting the case for larger randomized trials in this difficult-to-treat population.
tVNS® led to a reduction of depression-specific HAMD score of a minimum of 2-3 points in adult patients when used in parallel with psychopharmacological and psychotherapy treatments after a period of 9 weeks.
A randomized crossover trial of 33 depressed and 30 non-depressed adolescents found that acute taVNS did not improve general emotion recognition accuracy but did alter response inhibition on an emotional Go/NoGo task. Notably, taVNS reduced responses to sad stimuli in depressed adolescents while improving overall recognition in controls, suggesting the stimulation may specifically modulate negative-valence processing in adolescent depression.
tVNS® led to a reduction of depression-specific HAMD score of a minimum of 2-3 points in adult patients when used in parallel with psychopharmacological and psychotherapy treatments after a period of 9 weeks.
A non-blind case series of five adults with Prader-Willi Syndrome found that four hours of daily taVNS over 12 months produced significant reductions in temper outbursts in four of five participants, with improvements emerging around month nine. Halving the stimulation time to two hours reversed gains in most participants, suggesting sustained high-dose stimulation is necessary to maintain therapeutic effects.
Treatment with tVNS® led to a reduction of 50% of the frequency of days with chronic migraines after a treatment period of 12 weeks.
A systematic review and meta-analysis of 14 studies covering 995 patients found that preventive transcutaneous nerve stimulation reduced headache frequency by roughly 3 days per month in both episodic and chronic migraine, with episodic migraine patients also experiencing meaningful reductions in pain severity. The authors concluded that transcutaneous stimulation represents a clinically significant non-pharmacologic migraine prevention option.
Treatment with tVNS® led to a reduction of 50% of the frequency of days with chronic migraines after a treatment period of 12 weeks.
A 12-month case series of five Prader-Willi Syndrome patients found that daily taVNS significantly increased heart rate variability and reduced resting heart rate, both indicating enhanced vagal activity. Higher HRV levels predicted fewer emotional outbursts, suggesting taVNS may improve behavioral regulation by targeting autonomic nervous system dysfunction in this population.
After a treatment period of 12 months, 80% of tVNS® patients recorded a reduction of the mean number of outbursts per day of 50%, compared to the mean number of outbursts per day before treatment.
An ongoing randomized controlled trial (currently recruiting) based at Maastricht University Medical Center testing 8 weeks of taVNS against sham in irritable bowel syndrome patients. Primary outcomes include symptom reduction, quality of life, anxiety, and depression. The study also aims to determine whether a pre-treatment autonomic and brain imaging “neurosignature” can predict who will respond to taVNS.
After a treatment period of 12 months, 80% of tVNS® patients recorded a reduction of the mean number of outbursts per day of 50%, compared to the mean number of outbursts per day before treatment.
A non-blind case series of five adults with Prader-Willi Syndrome found that four hours of daily taVNS over 12 months produced significant reductions in temper outbursts in four of five participants, with improvements emerging around month nine. Halving the stimulation time to two hours reversed gains in most participants, suggesting sustained high-dose stimulation is necessary to maintain therapeutic effects.
After a treatment period of 12 months, 80% of tVNS® patients recorded a reduction of the mean number of outbursts per day of 50%, compared to the mean number of outbursts per day before treatment.
The tVNS® E is currently the only transcutaneous vagus nerve stimulation device approved in Europe according to the new Medical Device Regulation (MDR EU 2017/745). The tVNS® E is explicitly approved for the following indications:
Among patients who completed the 20-week trial, the 25-Hz group showed a significant 34.2% reduction in seizures compared with the control group; treatment adherence was high.
Those who responded to tVNS were able to reduce their seizure frequency by 60% after one year of tVNS treatment.
tVNS can reduce the frequency of epileptic seizures when used as an adjunctive treatment.
Ten studies involving 350 participants reported average reductions in seizure frequency of 30–65%. Some studies found improvements in quality of life and seizure severity.
Five prospective studies involving 118 patients with drug-resistant epilepsy and three randomised controlled trials involving 280 patients with drug-resistant epilepsy showed that tVNS can reduce seizure frequency by up to 64 per cent. In 65% of participants, seizure frequency improved by more than 50%.
The severity of depression decreased to a statistically significant extent. 80% achieved the predefined treatment goals.
Acute tVNS could have a beneficial effect on the processing of negative emotional stimuli in adolescents with depression.
tVNS was well tolerated in the treatment of depression in an adolescent patient and was associated with a clinically significant improvement in depression.
After two weeks of using tVNS, an improvement in self-reported symptoms was observed, and after four weeks, improvements were noted in both self-reported and clinician-assessed symptoms.
A 1 Hz tVNS reduced the number of headache days per month by 7, compared with a reduction of 3.3 days achieved with 25 Hz stimulation. 29.4% (1 Hz) versus 13.6% (25 Hz) achieved at least a 50% reduction in the number of headache days.
Low-frequency tVNS can reduce the number of migraine days and the severity of pain in migraine sufferers.
Among the study participants, a statistically significant reduction in the frequency and severity of outbursts of anger was observed after approximately nine months of daily four-hour tVNS treatment. A reduction in the daily treatment duration during the second part of the study resulted in a return to baseline levels.Among the study participants, a statistically significant reduction in the frequency and severity of outbursts of anger was observed after approximately nine months of daily four-hour tVNS treatment. A reduction in the daily treatment duration during the second part of the study resulted in a return to baseline levels.
tVNS could stabilise the autonomic balance in Prader-Willi syndrome and thereby reduce emotional outbursts.
We are proud that tVNS® is currently being investigated worldwide in various clinical and scientific contexts by high-profile research institutions. But where is the journey heading? Future developments aim to further improve application safety, personalisation, and integration into existing care concepts. The perspectives described below represent research and development directions and are not to be understood as clinical recommendations or approved applications.
Further development towards individualised neuromodulation. Current tVNS® applications mostly use predefined stimulation parameters. Future research approaches are examining whether an individual adaptation of frequency, intensity, and stimulation patterns is possible and meaningful.
Among other things, the following measurement methods are being evaluated:
The goal is better alignment of stimulation with individual neurophysiological differences, subject to corresponding clinical evidence and regulatory assessment.
Current tVNS® systems generally operate in an open-loop mode with fixed stimulation programmes. Research is investigating closed-loop approaches in which physiological signals could be used to dynamically adjust stimulation.
Possible control variables include:
These systems are still experimental and require comprehensive safety, clinical, and regulatory evaluation before any potential medical use.
Each year, more than 15 million people worldwide suffer a stroke. Many are left with weakness in the arm afterwards, making everyday tasks such as eating, dressing, or writing more difficult. Although rehabilitation therapy is a central component of stroke treatment, functional improvements are often limited. New approaches are therefore being investigated to specifically enhance the effects of rehabilitation.
Earlier studies have shown that stimulation of the vagus nerve during targeted movements can improve recovery of arm function after stroke. However, these studies used invasive vagus nerve stimulation (iVNS), in which a stimulator had to be surgically implanted. Stimulation could only be triggered in the clinical setting. The TRICEPS study is the first large-scale study to investigate whether this effect can also be achieved using a non-invasive method.
The main objective of the TRICEPS study is to examine whether tVNS® in combination with rehabilitation therapy can improve arm function after stroke more than rehabilitation alone.
In addition, it will assess:
In an accompanying sub-study, selected participants will undergo:
This will investigate whether tVNS® triggers neuroplastic changes in the brain that are associated with functional improvements in arm movement.
The TRICEPS study is one of the largest clinical trials of non-invasive vagus nerve stimulation in stroke rehabilitation.
It may provide important insights into:
