Neuromodulation Devices for Migraine

In recent years, neuromodulation has emerged as a promising means of migraine treatment. Essentially, neuromodulation is the use of a device to block or normalize pain signals — much like restarting a computer when it isn’t functioning properly. Exactly how this reset is accomplished is not entirely clear, but it may work by enhancing the body’s own natural pain-reducing response, including the release of anti-pain substances and turning on pathways that inhibit pain.

Neuromodulation can be performed through application of chemical, medicinal, or electrical stimuli. Non-invasive electrical neuromodulation will be the focus of this article.

There are many reasons why non-invasive neuromodulation is an attractive option for the treatment of migraine. It is typically well tolerated with minimal to no side effects. Some patients use it in addition to acute and preventive migraine medication. Others may use it due to a personal preference to avoid or minimize medication use. However, a significant drawback is the current lack of coverage by most insurance plans.

All devices discussed in this article are FDA-approved for the treatment of migraine and require a prescription. Devices are listed in chronological order of FDA approval.

Cefaly Dual

What: External trigeminal nerve stimulation (eTNS) device. The device is applied to the forehead with an adhesive electrode.

FDA approved: In 2014 for the preventive treatment of migraine in adults and in 2017 for the acute treatment of migraine in adults. In 2020 it was approved as an over-the-counter product for both the acute and preventive treatment of migraine in adults.

How it works: The trigeminal nerve is one of the primary nerves that transmits pain sensation from the face and head to the brain. Its dysfunction is thought to play a significant role in the cause of migraine.

• • For acute treatment of migraine, the device is worn for one hour.
  • For prevention, it is used for 20 minutes daily in “prevent” mode.
  • Many patients describe a tingling or a pressure sensation, which may be uncomfortable in patients with cutaneous allodynia, an increased pain sensitivity of the skin.

Clinical trials: Acute treatment resulted in pain relief in about 80% of patients and total pain freedom in about one-third of patients after one hour. Preventive treatment after three months of daily use resulted in a 50% reduction in the number of migraine attacks, and a 75% decrease in the use of acute medications.

Caution: Not recommended for patients with an implanted metallic or electronic device in the head, pain of unknown origin, a cardiac pacemaker or implanted or wearable defibrillator. The safety of use during pregnancy should be discussed with a physician.

Cost: $499. Replacement electrodes, which can each be used daily for about a month, come in a 3-pack for $25.

eNeura sTMS

What: Single-pulse TMS (sTMS) device. This rectangular device is used by placing it behind the back of the head and pressing a button, which delivers the single pulse instantly.

FDA approved: In September 2017 for the acute and preventive treatment of migraine.

How it works: sTMS may work by blocking cortical spreading depression (CSD, a slow moving wave which activates cells on the surface of the brain; and the cause of migraine aura) and thalamocortical signaling (communication between deep pain centers and the surface of the brain).

• • Acute treatment consists of three pulses repeated up to three times for each attack.
  • Preventive treatment consists of four pulses delivered twice daily.
  • Most common side effects in studies were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious side effects.

Clinical trials: Acute treatment of migraine with aura after two hours resulted in higher pain-free response rates (39%) than with sham stimulation, and rates remained higher 48 hours post-treatment. The benefit from acute treatment may be less in patients without aura. Preventive treatment after twice daily use of sTMS for 3 months resulted in a decrease of migraine days per month by 2.75, and about half of the patients experienced a 50% reduction in migraine frequency. Many patients also experienced a reduction in days of acute medication use and decreased disability.

Cost: $250 per month.

gammaCore Sapphire

What: Non-invasive vagal nerve stimulation (nVNS) device. The hand-held device has two metal contacts that are pressed lightly against the neck with use of a gel, in the area of the carotid pulse.

FDA approval: In 2018 for the acute treatment of pain associated with migraine, and in 2020 for the preventive treatment of migraine.

How it works: The vagus nerve originates in the brain stem and carries both motor and sensation signals to and from the body. The vagus nerve is responsible for many of the autonomic (non-voluntary) function of internal organs including the heart, the stomach and intestines, and others. It also serves as a communication system between the body and brain and has a role in regulating pain transmitters and inflammation levels.

• • For acute treatment, stimulation is applied for two minutes and immediately repeated for another two minutes (on same or alternating sides of neck). After 20 minutes, if pain remains, the patient can conduct a second round of treatment. If pain remains after two hours, the patient may repeat a third round.
  • For prevention, one round of treatment is used three times daily, with about 6 hours between rounds.
  • Some patients experience a tingling sensation, which may cause discomfort. This occurs to a less frequent extent compared to Cefaly.

Clinical trials: Almost half of patients had little to no migraine pain within 2 hours after first use, and the majority of patients who were pain-free at 2 hours remained pain-free for 48 hours. Some patients experienced relief as quickly as 30 minutes. Prevention treatment for patients with chronic migraine (more than 15 headache days per month) found that 2 months of daily stimulation resulted in 1.4 fewer headache days per month. Some study patients went on to use the device for an additional 6 months, resulting in 7.9 fewer headache days per month compared to baseline.

Caution: Not indicated in pregnant or pediatric patients, or patients with a variety of medical comorbidities including but not limited to carotid stenosis, cancer, seizures, arrhythmias and other brain and heart disorders. It should not be used in patients with implanted metallic or electrical devices.

Cost: $600 per month.

Nerivio

What: Remote electrical neuromodulation (REN) device. It is applied to the upper arm.

FDA approval: In May 2019, for the acute treatment of episodic migraine (less than 15 headache days per month) with or without aura.

How it works: The electrical signals from the arm communicate with the pain centers in the brain and activate pain control pathways. The Nerivio stimulates the upper arm peripheral nerves to induce conditioned pain modulation.

• • Stimulation is applied for 45 minutes.
  • Mild adverse events in studies, occurring in about 5% of patients, included warmth sensation, temporary arm/hand numbness, redness, itching, tingling, muscle spasm, and pain in the arm, shoulders, or neck.

Clinical trials: Acute treatment with Nerivio was more effective than sham stimulation in achieving pain relief in 67% vs 39%; total resolution of pain in 37% vs 18%; and most bothersome symptom relief (nausea, sensitivity to light or sound) in 46% vs 22% at 2 hours post‐treatment. The higher rates of pain relief and pain freedom was sustained 48 hours post‐treatment.

Caution: Not for people with congestive heart failure, severe cardiac or cerebrovascular disease, or uncontrolled epilepsy; or for anyone with active implantable medical devices (pacemaker, hearing aid implant, etc). It should only be applied on the upper arm over dry, healthy skin with normal physical sensation and without any metallic implants or in proximity to cancerous lesions.

Cost: Each Nerivio device costs $99 and delivers twelve 45-minute treatments.

Patients have different treatment needs, and these differences may determine which device to use. The number and duration of migraine attacks you experience, other medical conditions, and the presence of allodynia or aura may play a role in which device would be best for you. Speak with your physician about which devices may be most appropriate for you.