SAN FRANCISCO—The rapidly growing bank of data about devices for neuromodulation may soon change the way neurologists manage patients with headache, according to an overview presented at the Eighth Annual Winter Conference of the Headache Cooperative of the Pacific. When the devices become broadly available, neurologists could first consider treatment with the least invasive devices that have the fewest adverse events before trying medications or progressively more invasive methods, said Stewart J. Tepper, MD, Professor of Medicine (Neurology) at the Cleveland Clinic Lerner College of Medicine. “The future is going to be real soon,” he added.
Transcutaneous Supraorbital Neurostimulation
The first noninvasive device to receive FDA approval was Cefaly, a transcutaneous supraorbital neurostimulator (tSNS), which is indicated for preventive treatment of migraines. The device was approved in March 2013, after it had already been approved in Europe and Canada. In 2013, Schoenen et al randomized 67 patients with episodic migraine with or without aura to sham stimulation or tSNS at five tertiary centers. After they recorded baseline measurements, patients were instructed to wear the device for 20 minutes per day for three months. The researchers did not observe a significant change in monthly migraine days at three months, which was one of the two primary outcome measures. Approximately 38% of patients, however, had a reduction in migraine days per month of at least 50%, which was the other primary end point. The investigators saw a significant change in the number of headache days per month among treated patients, and the therapeutic gain increased with the duration of treatment.
Elements of the study may raise concerns about the device. Although the patients had no adverse events, according to the researchers, they had strong paresthesias. Adherence in the study was low; patients completed an average of 55 of 90 treatment sessions.
An open-label follow-up study examined 2,313 participants who rented the tSNS device for a 40-day trial period. Approximately 53% of participants were willing to buy the device, and 47% were dissatisfied and returned it. Users of the returned devices had turned them on for about half of the required time. The approximate level of evidence for the device is B, probably effective, said Dr. Tepper. The tSNS device is available for patient purchase with a doctor’s prescription in the United States.
Transcranial Magnetic Stimulation
Transcranial magnetic stimulation (TMS) is another noninvasive technique that researchers have studied as a headache treatment in several trials. Results generally have been positive, but the studies’ methodologic heterogeneity makes it difficult to draw conclusions from them. By 2014, three randomized controlled trials had examined the efficacy of repetitive TMS at preventing migraine. Three of the studes were positive, and one was negative, so conclusions are uncertain.
In May 2014, the FDA approved a single-pulse TMS (sTMS) device for the acute treatment of pain associated with migraine with aura (Spring TMS). The device is approved in the United Kingdom. The level of evidence for TMS in this indication is B, probably effective, said Dr. Tepper, based on a positive randomized controlled trial in which the patient activated the device with two pulses within one hour of the onset of aura. Several American centers, currently the only places that patients can access these FDA-approved devices, are conducting postmarketing studies of the sTMS device. Evidence for sTMS for the acute treatment of migraine with aura is level B, probably effective. Evidence for TMS in migraine prevention is level U because the data are conflicting. Future randomized, controlled trials of TMS should determine the proper dose, study the technique’s efficacy in migraine without aura and in prevention, and analyze the safety of long-term treatment, said Dr. Tepper.
Vagal Nerve Stimulation
In a randomized controlled trial in 2014, Gaul et al compared the standard of care for cluster headache plus a noninvasive, handheld vagal nerve stimulation (VNS) device (gammaCore) with standard of care alone. VNS plus standard of care reduced the number of cluster headache attacks per week and decreased patients’ use of rescue medications and oxygen. Longer treatment duration was associated with better efficacy. VNS is probably effective for acute and preventive treatment of cluster headache, said Dr. Tepper.
Also in 2014, Silberstein et al conducted a sham-controlled study of VNS in patients with chronic migraine. The treatment did not meet the primary end point, but the treatment group had a clinically meaningful decrease in headache days during an open-label extension. Adverse events were minor and included neck discomfort and twitching. Data for VNS in migraine are inadequate or conflicting, said Dr. Tepper, but if one in four patients with cluster headache responds to VNS, “why wouldn’t we use that before we give them injectable sumatriptan or oxygen?” The noninvasive VNS device is currently approved in Europe and Canada.