ARTICLE IN BRIEF
Migraine experts assess the clinical utility of a newly approved Food and Drug Administration device for migraine, which applies transcutaneous electrical nerve stimulation to the trigeminal nerve.
The US Food and Drug Administration (FDA) approved the marketing of Cefaly, a transcutaneous electrical nerve stimulation (TENS) device for prevention of migraine on March 11. But while migraine experts told Neurology Today the approval is a generally welcome advance that may be helpful to some patients, they said evidence is far from conclusive, noting that the “performance bar” for medical devices is much lower than it is for pharmaceuticals and that patients should not expect a panacea.
The small, portable, battery-powered, TENS device resembles a plastic headband worn across the forehead and atop the ears, using a self-adhesive electrode. The device, which can cost about $350, applies an electric current to the skin and underlying body tissues to stimulate branches of the trigeminal nerve, which has been associated with migraine headaches. The user may feel a tingling or massaging sensation where the electrode is applied. The device is indicated for patients 18 years of age and older and should only be used once per day for 20 minutes, according to FDA.
The approval was based on a relatively small Belgian study that found the device to be safe and well-tolerated and a larger survey of patients who used the device for 40 days.
In the smaller study, published first online last February as a supplement of the Journal of Headache and Pain, researchers from the Centre Hospitalier Regional de la Citadelle in Liege, Belgium, assessed satisfaction with the device in 67 patients who experienced more than two migraines per month, and who had not taken medications to prevent migraines for three months before using the device. They also reviewed data from a patient-satisfaction study of 2,313 migraine patients in Belgium and France — published Dec. 1, 2013 in the Journal of Headache and Pain — who rented it for a 40-day trial period via the Internet.
Subjects using specific anti-migraine drugs were included in the survey. Adverse events and willingness to continue using the device were monitored via phone interviews after the trial period. Built-in software also allowed for monitoring the total duration of use and compliance in subjects who returned the device to the manufacturer after the trial period.
According to the FDA, the 67-person study showed that those who used the TENS device had significantly fewer days with migraines per month and used less migraine medication than those who used a placebo device. The device did not completely prevent migraines and did not reduce the intensity of migraines that did occur.
In the larger patient-satisfaction study, after a testing period of 58.2 days on average, 46.6 percent of the 2,313 renters were not satisfied and returned the device, but a compliance check showed that they used it only for 48.6 percent of the recommended time. The remaining 54.4 percent of subjects reported being satisfied with the treatment and were willing to purchase the device. Ninety-nine subjects out of the 2,313 reported one or more adverse events, but none were serious; the most frequent were local pain/intolerance to paresthesia (47 subjects), arousal changes (mostly sleepiness/fatigue, sometimes insomnia), and headache after the stimulation. A transient local skin allergy was seen in two subjects.
In a statement accompanying the FDA's approval of the device, Christy Foreman, director of the Office of Device Evaluation at the FDA's Center for Devices and Radiological Health, said the TENS device provides an alternative to medication for migraine prevention. “This may help patients who cannot tolerate current migraine medications for preventing migraines or treating attacks,” she said.
The FDA reviewed the for the device through the de novo premarket review pathway, a regulatory pathway for generally low- to moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.
WHAT EXPERTS THINK
Stephen Silberstein, MD, FAAN, a professor of neurology and director of the Headache Clinic at the Jefferson University School of Medicine, said the evidence for effectiveness was not overwhelmingly convincing. Because it appears to be completely safe, it may be worthwhile to offer to patients who are reluctant to take medication, or as an adjunct to medication.
In his own practice, Dr. Silberstein said he has offered the device to a few patients with modest reports of effectiveness. And he said even such limited effectiveness may be short-lived.
Morris Levin, MD, FAAN, a professor of neurology and psychiatry at the Geisel School of Medicine at Dartmouth, said he believes the evidence for the usefulness of the device is not sufficient because of the difficulty in designing a study in which both subjects and researchers are blinded. “It seems to be nothing more than a TENS unit and I think a number of people will seem to improve with it initially, similar to what has been seen in the past with TENS, but this will mostly be placebo effect,” he told Neurology Today. “On the positive side, it seems to be very easy to learn how to use and will probably do no damage.”
Deborah I. Friedman, MD, FAAN, a professor of neurology, neurotherapeutics, and ophthalmology at the University of Texas Southwestern Medical Center, noted that the Belgian study was well done, that the device is certainly safe, and that there are some patients who are likely to benefit. But, she added, she and colleagues in the field were surprised by the amount of publicity that accompanied the approval.
“I think we need a bigger study and more experience using these devices for a longer period of time,” she said. “Many of these devices appear to work in the beginning but effectiveness is not prolonged.”
Todd Schwedt, MD, an associate professor of neurology at the Mayo Clinic in Phoenix, was slightly more optimistic. “Since transcutaneous supraorbital nerve stimulation is a non-invasive and relatively safe therapy with a mechanism of action that differs from typically used migraine prophylactic treatments, I anticipate that there will be interest in adding this new modality to the migraine treatment armamentarium,” he told Neurology Today.
“Larger clinical trials would give a better estimate of the responder rate and might allow for identification of baseline patient characteristics that increase the likelihood for therapeutic response,” Dr. Schwedt added.
Dr. Silberstein agreed that the device, whatever its limitations, represents a small advance in a field of transcutaneous nerve stimulation for migraine that is likely to continue to grow. “This is the beginning of the story, not the end,” he said.
•. Schoenen J, Vandersmissen B, Jeangette S, et al. Prevention of migraine by supraorbital transcutaneous neurostimulation using the Cefaly® device (PREMICE): A multi-centre, randomized, sham-controlled trial. J Headache Pain. 2013;14:(Suppl 1): P184; E-pub 2013 Feb. 21.
•. Magis D, Sava S, d'Elia TS, et al. Safety and patients' satisfaction of transcutaneous supraorbital neurostimulation (tSNS) with the Cefaly® device in headache treatment: A survey of 2,313 headache sufferers in the general population. J Headache Pain. 2013; 14:95.
•. Silberstein SD, Hollad S, Freitag F, et al. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012; 78: 1337–1346.