TMS Device May Offer Nondrug Option for Migraine Prevention

Damian McNamara

April 12, 2018

A US Food and Drug Administration (FDA)–approved device that delivers single-pulse transcranial magnetic stimulation (sTMS)  to the brains of people with frequent migraines reduced the number of headache days by almost one third, new research shows.

Results of the multicenter, prospective, open-label study showed 3 months of daily treatment with the SpringTMS device (eNeura Inc) was also associated with improvements in several secondary measures.

The 50% responder rate, days of acute medication use, headache impact scores on the Headache Impact Test-6 (HIT-6) and reduction in days with a headache of any intensity each surpassed a performance goal. Participants also used the device for acute migraine treatment as needed.

"It's important to make sure patients have both a plan for prevention of attacks as well as a plan to treat a migraine that is ongoing," lead author, Amaal J. Starling, MD, from the Mayo Clinic in Phoenix, Arizona, told Medscape Medical News. "And single-pulse transcranial magnetic stimulation is another clinically available option we have now, one that has data for both acute attacks and prevention of attacks."

"There are so many people with migraines, and there are so many different treatment options, and this is one. It's important to have a variety of options. Each individual treatment may or may not be effective for each individual patient," she added.

The study was published online March 4 in Cephalalgia.

New Indication

The FDA initially cleared the portable device for treatment of acute migraine in May 2014. When the manufacturer sought to expand the indication to include migraine prevention, the agency considered the current eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) study, as well as a randomized controlled trial (Lancet Neurol. 2010;9:373-380) and pilot results of a UK postmarketing program (J Headache Pain. 2015;16:535).

The FDA granted the prevention indication in September 2017.

The study included adults who experienced migraine on at least 4 days per month and lasted for 4 hours or more. All were recruited from headache subspecialty clinics.

A total of 263 patients were enrolled between December 2014 and March 2016. After exclusions, a full analysis set (FAS) included 132 participants who served as the intent-to-treat cohort.

A completed cases (CC) group of 117 patients consisted of those who did not withdraw or who were not lost to follow-up.  A per protocol group of 95 people used the device as instructed for the entire 3 months.

About 90% of the FAS group had episodic migraines, and the remainder experienced chronic migraine.

Participants completed a 28-day paper diary of headache frequency and intensity before starting the 3-month protocol. Treatment was four pulses twice per day for prophylaxis.

Self-administered Treatment

Patients placed the device on their occiput and pressed a button to deliver sTMS. The 0.9-T pulse has a rise time of 180 microseconds and a total pulse length shorter than 1 millisecond.

The acute treatment protocol was three consecutive pulses. Patients could repeat acute treatment twice if they felt no relief after 15 minutes, and researchers allowed rescue medications after 30 minutes, if needed.

Mayo Clinic posted a 1-minute video with Starling demonstrating use of the device.

Repeated TMS may prevent migraine attacks by reducing cortical hyperexcitability, Starling said. sTMS may be effective for acute relief of migraine through inhibition of cortical spreading depression.

The 132 patients in the FAS group reported a mean 9.06 headache days per month at baseline. After treatment, this dropped by 2.75 days, a significant decrease compared to  the statistical performance goal of a 0.63-day fewer migraines (P < .0001).

Almost half, 46%, of 117 participants in the CC cohort experienced at least a 50% decrease in the number of headache days. The performance goal on this outcome was 20%. The reduction in the number of days with acute headache medication use decreased by a mean of 2.93 from baseline in the same group. Both these findings were statistically significant (P < .0001). 

The HIT-6 scores dropped by a mean of 3.10 in the CC group after treatment, an outcome significantly greater than zero (P < .0001).

The total number of days with a headache of any reported intensity dropped by 3.16 days compared to a performance goal of a 0.63-day decrease (P < .0001).

"It seems to be effective in people who have migraine with aura as well as patients without aura," Starling said.

Extensive Safety Data

The investigators also assessed safety.

"What is important to emphasize both to clinicians who are prescribing this, as well as to patients, is that this involves a magnetic pulse, a technology that has been available for years," she said.  "It's been used in both neurology and psychiatry both diagnostically and therapeutically, so there is a lot of safety data on this."

No serious adverse events were reported in the current research. Nine patients withdrew from the study because of adverse events. Of the total 62 adverse events recorded, investigators determined 16 were unrelated to treatment, 30 were possibly related, and 12 were thought probably or definitely related. The most common adverse events reported included lightheadedness, tingling, and tinnitus.

Oral migraine medications also cause side effects in some patients, Starling said.

"The single-pulse transcranial magnetic stimulation device is a great option for patients who don't tolerate oral medications. It's really safe; it's well tolerated. This may also be an option for people for whom other treatments have been ineffective, both to treat individual attacks and to prevent attacks from occurring in the first place."

The device is contraindicated in patients with a history of seizures and those with metal implants in their head, neck, or upper body, including a pacemaker or defibrillator.

"One of my areas of interest is trauma — concussion and post-traumatic headaches specifically," Starling said. "I would really like to explore the utility of this technology in post-traumatic headache."

With limited evidence for effective treatment in this patient population, the TMS device may be an effective option to address these headaches and symptoms of concussion, she added.

Also Good for Chronic Headache?

Commenting on the findings for Medscape Medical News, Huma Sheikh, MD, assistant professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City, described the study as "interesting" in that it shows sTMS is a potential alternative to oral preventive medications and that it met all four of its primary endpoints.

"However," she noted, "there were about 30 patients who did not complete the 3-month treatment either altogether or per protocol," she said. "This may speak to the ease of use for the device, which would determine rates of compliance in real-world use."

"The pros of this type of treatment include the fact that it works by targeting one of the major known mechanisms for the development of migraine, mainly cortical spreading depression. It is also a different type of treatment modality that would be very unlikely to interact with a patient's other medications," she added.  

Most of the patients in the study were diagnosed with episodic migraine than with chronic migraine.

"Therefore, it would be interesting to see if these results would also hold true for more severe patients with frequent or chronic daily headache," she said.

She also pointed to lack of a sham device comparison in the study, which the researchers acknowledge is a potential limitation, adding that it would be difficult to create a convincing sham device.

eNeura Inc supported the study. Starling is a member of the eNeura Advisory Board. Sheik has disclosed no relevant financial relationships.

Cephalalgia. Published online March 4, 2018. Full text

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