External trigeminal nerve stimulation system
Treatment of attention deficit hyperactivity disorder (ADHD)
Approved in the US, Canada, Europe, and Australia
NeuroSigma’s Monarch® external trigeminal nerve stimulation (eTNS®) system is a monotherapy approved for the treatment of paediatric attention deficit hyperactivity disorder (ADHD).
It is a prescription-only device and the company’s first non-drug treatment for ADHD patients. It is designed for at-home use under the supervision of physicians.
The Monarch eTNS system was first approved in Canada in May 2013 as a Class II medical device for drug-resistant epilepsy (DRE), major depressive disorder and treatment-resistant depression.
The Australian Therapeutic Goods Administration (TGA) approved the device in April 2014 as a supplementary treatment for DRE in patients aged nine years and older. The device received Humanitarian Use Device (HUD) designation from the US Food and Drug Administration (FDA) for the treatment of Lennox-Gastaut Syndrome (LGS) symptoms in January 2015.
In addition, the Monarch eTNS system received the European CE Mark in November 2015 and FDA clearance in April 2019 for the treatment of ADHD patients. The FDA approved the device via the de novo pathway under the classification name Transcutaneous Nerve Stimulator for ADHD.
Monarch eTNS system features
The Monarch eTNS system is a mild nerve-stimulating device. It comprises a portable pulse generator connected to a single-use electric patch, which is placed on the patient’s forehead.
Low-level electric signals are transmitted to the electrode patches, which stimulate trigeminal nerve fibres and send therapeutic signals to the areas of the brain known to be involved with ADHD.
Monarch eTNS mechanism of action
The trigeminal nerve is the fifth and the largest cranial nerve. It is directly connected to the brain and controls facial sensation. The nerve either directly or indirectly enters the regions of the brain associated with ADHD and other disorders.
TNS provides a mild electrical pulse to various branches of the trigeminal nerve and tends to increase the activity in the regions of the brain associated with regulating attention and behaviour.
Clinical trials on Monarch eTNS system
The FDA’s approval of the device was based on a pivotal, double-blind, randomised controlled trial conducted at the University of California, Los Angeles (UCLA). A total of 62 children with moderate-to-severe ADHD were enrolled in the trial.
The device was compared with placebo and used on patients for four weeks. The primary endpoint of the trial was improvement in ADHD-Rating Scale IV (ADHD-RS-IV) score, which is used to measure the severity of ADHD symptoms. A higher score on the scale indicates worsening symptoms.
At week four, children treated with the device demonstrated a decrease in ADHD-RS-IV score from 34.1 points to 23.4 points compared to a decrease from 33.7 points to 27.5 points in the placebo group. The safety profile of the device was also favourable.
Significant improvement in the clinical global impression improvement (CGI-I) scale was also observed in patients treated with the device compared to the placebo group.
Common side effects reported during the study were trouble sleeping, improved appetite, headache and teeth clenching.
Market commentary on NeuroSigma
Based in the US, NeuroSigma is a life sciences company involved in the development and marketing of bioelectronic technologies including eTNS.
The company’s TNS neuromodulation therapies are developed on the intellectual property exclusively licensed from the University of California, Los Angeles. The therapies cover a broad range of disorders such as ADHD, epilepsy and post-traumatic stress disorder.