Journal Articles

External Trigeminal Nerve Stimulation for Drug Resistant Epilepsy: A Randomized Controlled Trial

This publication details results from a randomized trial of external Trigeminal Nerve Stimulation (eTNS) in 40 patients with frontal or temporal drug resistant epilepsy that were not candidates for surgery. Patients were randomized 1:1 to receive adjunctive eTNS or usual medical treatment and evaluated at 3, 6, and 12 months. At 12 months there was a 50% responder rate among patients receiving eTNS as compared to 0% in the control group. eTNS was well tolerated with no serious adverse events observed.

Double-Blind, Sham-Controlled, Pilot Study of Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder.

Published in the Journal of the American Academy of Child and Adolescent Psychiatry. This presents results from the first double-blind randomized controlled trial of external Trigeminal Nerve Stimulation (eTNS) for treating pediatric ADHD. The trial achieved statistical significance on its primary endpoint, the ADHD-RS scale. The trial also found significant changes in EEG recordings among subjects enrolled in the treatment group as compared to those in the sham group.

J Am Acad Child Adolesc Psychiatry, 2019.

Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder.

This paper reports the first open pilot study of eTNS as an adjunctive therapy for adults with PTSD and co-occuring major depression. 12 adults with moderate-to-severe symptoms that had not responded to medication treatment received eTNS nightly for 8 weeks. Significant reductions in severity were found for both PTSD and depression symptoms, and the treatment was generally well tolerated. Quality of life measures also improved significantly.

Neuromodulation, 2016.

An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder.

The first pediatric trial of eTNS examined its use in children with ADHD as a single primary treatment (monotherapy) rather than adjunctive therapy. 24 children, ages 7-14, used eTNS nightly for 8 weeks. Significant improvements were found in the symptoms of ADHD and also in computerized measures of cognitive function. The investigators reported that TNS was well accepted by patients and families, treatment compliance was high, and there were no clinically meaningful side effects.

Brain Stimulation, 2015.

The potential use of trigeminal nerve stimulation in the treatment of epilepsy.

This summary paper describes some of the unmet medical need that has driven innovation with eTNS for epilepsy.

Therapeutic delivery, 2015.

Effects of Adjunctive Trigeminal Nerve Stimulation in Major Depressive Disorder in a Dose Ranging Trial.

This poster shows results from a double-blind dose ranging trial of eTNS for Major Depressive Disorder. Data from the initial 6-week phase of the 12-week cross over protocol are presented. Active eTNS was associated with a significantly greater symptom reduction than sham, and similar benefits across a wide range of stimulation frequencies.

First International Brain Stimulation Conference, Singapore, 2015

Neuromodulation for Depression Invasive and Noninvasive (Deep Brain Stimulation, Transcranial Magnetic Stimulation, Trigeminal Nerve Stimulation).

This review paper describes several neuromodulation therapies for use in depression, including eTNS, and provides key references to the scientific literature.

Neurosurgery Clinics of North America, 2014.

External Trigeminal Nerve Stimulation (eTNS) for Epilepsy: Early Clinical Experience.

A poster presented by a Slaght et al. from the Department of Neurology at King’s College, London. Their early clinical experience with eTNS for epilepsy shows a median reduction in seizure frequency of 38% after 12 weeks of treatment, along with a 38% responder rate at that time. Improvements in mood and quality of life were also observed. These findings confirm results from earlier studies of eTNS for epilepsy.

European Congress on Epileptology, Stockholm, 2014

Efficacy and safety of Trigeminal Nerve Stimulation: An experience in 8 patients with drug-resistant epilepsy

A poster presented by a Sierra-Marcos et al. from the Epilepsy Unit of the Neurology Service at Fundación Jiménez Díaz University Hospital, Madrid, Spain. Their poster presents their preliminary experience with 8 patients, and shows a responder rate of 43% among patients who used the device for 24 weeks.

European Congress on Epileptology, Stockholm, 2014

Neuromodulation for depression: invasive and noninvasive (deep brain stimulation, transcranial magnetic stimulation, trigeminal nerve stimulation)

A review of several neuromodulation therapies used for the treatment of depression and other neuropsychiatric disorders, including trigeminal nerve stimulation.

Neurosurgery Clinics of North America, 2014

Trigeminal nerve stimulation in major depressive disorder: Acute outcomes in an open pilot study.

A comprehensive description of the first open pilot investigation of eTNS as adjunctive therapy for major depression. 11 adults with treatment resistant depression received eTNS nightly for 8 weeks. At the end of the trial there were significant reductions in symptom severity on both clinician and patient rating scales. The average decrease in symptom severity was 51%, and 4 of 11 patients achieved remission. There were no serious adverse events during the trial.

Epilepsy and Behavior, 2013

Randomised controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy.

This paper details results from the first ever double-blind, randomised controlled trial of eTNS for treatment of drug resistant epilepsy. The study found that after 18 weeks of eTNS 40.5% of patients in the treatment group reduced their seizure frequency by 50% or more, versus only 15.6% of patients in the control group. Patients in the treatment group also demonstrated significant improvements in mood that were independent of their change in seizure frequency.

Neurology, 2013

Central mechanisms of cranial nerve stimulation for epilepsy.

An in-depth review of cranial nerve stimulation techniques for the treatment of epilepsy that discusses mechanisms of action for how these treatments produce their anti-seizure effects and identifies areas for future investigation.

Surgical Neurology International, 2012

Benefits of trigeminal nerve stimulation.

An editorial written by Dr. Robert Fisher of Stanford University. Dr. Fisher is a pioneer in the field of neuromodulation approaches for treating epilepsy. In this editorial, Dr. Fisher discusses the benefits of trigeminal nerve stimulation and the exciting data that has been produced to date.

Epilepsy & Behavior, 2012

Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy.

A publication examining the short- and long-term safety data associated with use of eTNS. Notably, there have been no significant adverse events associated with the use of eTNS therapy to date.

Epilepsy & Behavior, 2011

Trigeminal nerve stimulation: seminal animal and human studies for epilepsy and depression.

An overview of the pre-clinical animal work and early clinical studies. The work first demonstrated the anti-seizure effects of TNS as well as the first clinical studies of non-invasive eTNS therapy for drug resistant epilepsy.

Neurosurgery Clinics of North America, 2011

Trigeminal nerve stimulation in major depressive disorder: first proof of concept in an open pilot trial.

This manuscript details interim results from the first-ever trial of eTNS as adjunctive therapy for major depressive disorder. Patients were resistant to medication and used eTNS nightly for 8 weeks. At the end of the trial, patients demonstrated a mean decrease in symptom severity of 52%, indicating a robust anti-depressant effect of eTNS in this preliminary study.

Epilepsy & Behavior, 2011

Trigeminal nerve stimulation for epilepsy: long-term feasibility and efficacy.

Results from the Phase I study of eTNS for drug resistant epilepsy. Thirteen subjects with severe drug resistant epilepsy (an average of 2.1 seizures/day) were enrolled to receive eTNS for 12 weeks. Twelve of 13 subjects completed the study. Average seizure frequency decreased from 2.1 seizures/day to 0.71 seizures/day. Importantly, these results were sustained in long-term follow-up at 6 and 12 months.

Neurology, 2009

Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial.

Results from seven subjects treated with eTNS for their drug resistant epilepsy. Four of seven subjects (57%) had a greater than 50% reduction in seizure frequency.

Epilepsia, 2006

Trigeminal nerve stimulation for epilepsy.

The first publication to provide clinical results on the use of eTNS for treatment of drug resistant epilepsy. This case/series details the experience of the first two patients treated with eTNS.

Neurology, 2003

Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation.

Details of the pre-clinical animal work demonstrating that TNS has an anti-seizure effect. A series of studies using a rat seizure model showed that high-frequency, bilateral stimulation of the trigeminal nerve results in dramatic reductions in seizure activity. The Monarch eTNS system employs a similar strategy of bilateral, high-frequency stimulation, which may improve efficacy as compared to other cranial nerve stimulation therapies.

Journal of Neuroscience, 2000

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