Monday, April 22, 2019

External trigeminal nerve stimulation for attention-deficit/hyperactivity disorder


The US Food and Drug Administration (FDA) has granted marketing authorization to NeuroSigma for its Monarch external trigeminal nerve stimulation (eTNS) system. It is the first device to treat attention-deficit/hyperactivity disorder (ADHD), the agency announced.

The eTNS system will be available by prescription only and is indicated for children aged 7 to 12 years who have not already been prescribed an ADHD medication.

"This new device offers a safe, non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind," Carlos Peña, PhD, director of the Division of Neurological and Physical Medicine Devices in the Center for Devices and Radiological Health at the FDA, said in a news release.

The agency noted that the cell phone–sized stimulation system is intended to be used in the home under the supervision of a caregiver while the patient sleeps. A small patch adheres to the forehead above the eyebrows and is connected via wire to the system, which gives off a low-level electrical pulse.

This resulting pulse "should feel like a tingling sensation on the skin," the FDA said. They added that the pulse stimulates parts of the trigeminal nerve and signals parts of the brain associated with ADHD.
Mechanisms of action for the system are still unknown, but previous neuroimaging studies "have shown that eTNS increases activity in the brain regions that are known to be important in regulating attention, emotion, and behavior," the agency noted.

Trials have suggested that evidence of a response could take up to 4 weeks.


In one study involving 62 children with moderate to severe ADHD, those who were randomly assigned to receive treatment with the eTNS device showed significant improvement in symptoms on a clinician-administered ADHD rating scale compared with their peers who received matching placebo (10.7-point decrease from baseline vs 6.2-point decrease). This outcome met the trial's primary endpoint.
Drowsiness, sleep difficulties, increased appetite, headache, fatigue, and teeth clenching are the most common side effects that have been observed with the system. However, no serious adverse events have been associated with the device, the FDA said.

As reported by Medscape Medical News, eTNS has been previously associated with positive outcomes for other conditions, including episodic and chronic migraine, major depression, and epilepsy.

In its statement, the FDA cautioned that the system should not be used in patients younger than 7 years or in anyone who has an active implantable pacemaker, an active implantable neurostimulator, or a wearable device, such as an insulin pump. It should also not be used near an MRI machine, cell phones, or other entities with radiofrequency energy.

"Today's action reflects our deep commitment to working with device manufacturers to advance the development of pediatric medical devices so that children have access to innovative, safe, and effective medical devices that meet their unique needs," Peña said.

According to the manufacturer's website, a starter kit for the device costs about $1000 and is not currently covered by insurance.


The Monarch eTNS System’s efficacy in treating ADHD was shown in a clinical trial that compared eTNS as the sole treatment, or monotherapy, to a placebo device. A total of 62 children with moderate to severe ADHD were enrolled in the trial and used either the eTNS therapy each night or a placebo device at home for four weeks. The trial's primary endpoint was improvement on a clinician-administered ADHD Rating Scale, ADHD-RS.  ADHD-RS scales are used to monitor severity and frequency of ADHD symptoms. A higher score is indicative of worsening symptoms. The ADHD-RS uses questions about the patient’s behavior, such as whether they have difficulty paying attention or regularly interrupt others. The trial showed that subjects using the eTNS device had statistically significant improvement in their ADHD symptoms compared with the placebo group. At the end of week four, the average ADHD-RS score in the active group decreased from 34.1 points at baseline to 23.4 points, versus a decrease from 33.7 to 27.5 points in the placebo group…

The Monarch eTNS System should not be used in children under seven years of age. It should not be used in patients with an active implantable pacemaker or with active implantable neurostimulators. Patients with body-worn devices such as insulin pumps should not use this device. The eTNS System should not be used in the presence of radio frequency energy such as magnetic resonance imaging (MRI), because it has not been tested in an MRI machine, or cell phones, because the phone’s low levels of electromagnetic energy may interrupt the therapy.

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