Nonpharmacologic treatment shows efficacy for episodic migraine

Noninvasive vagus nerve stimulation (nVNS) may be an effective treatment for pain in patients with episodic migraine up to 60 minutes after an acute attack, according to a new study published in Neurology.

“The multiple pharmacologic classes that are effective for the acute treatment of migraine are sometimes limited by lack of availability or risks of drug interactions, medication overuse, and adverse events (AEs),” wrote authors, led by Cristina Tassorelli, MD, PhD, Headache Science Centre, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy. “Practical alternatives, such as noninvasive neuromodulation therapies that are effective, safe, and well-tolerated, are attractive for early, adjunct, or frequent use when standard pharmacologic interventions are largely unavailable or ineffective.”

During pilot studies, nVNS demonstrated efficacy in treating acute migraine and was shown to be convenient, practical, safe, and well tolerated. The device produces a proprietary low-voltage electrical signal (5-kHz sine wave burst) that lasts for 1 millisecond, with bursts repeated every 40 milliseconds.

In the PRESTO study, one of the largest randomized, double-blind, sham-controlled studies of a noninvasive neuromodulation device for the acute treatment of migraine, Dr. Tassorelli and colleagues compared treatment outcomes between nVNS and a sham device treatment in patients with episodic migraine. The researchers also assessed the safety and tolerability of nVNS.

Investigators randomized a total of 248 patients with episodic migraine with/without aura to receive nVNS or sham within 20 minutes from pain onset. Patients were to repeat treatment if pain had not alleviated within 15 minutes of initial treatment. Results were evaluated from 243 patients: nVNS (n=120) and sham (n=123).

The team required that patients taking preventive migraine medications before initiation of the study maintain stable dose and frequency of these drugs within the 2 months before enrollment. Patients were not allowed to start new preventive medications during the study.

The primary outcome for the current study was the fraction of patients who were pain free at 120 minutes following completion of treatment without the need for rescue medications. Secondary outcomes included other pain measures at 30, 60, and 120 minutes. The team defined pain relief according to International Headache Society (IHS) guidelines.

At 30 and 60 minutes after treatment, nVNS outperformed the sham device at aborting the initial migraine attack (12.7% vs 4.2%; P=0.012 and 21.0% vs 10.0%; P=0.023, respectively),but not at 120 minutes (30.4% vs 19.7%, P=0.067). Researchers performed a repeated measures test to gain additional insight into the primary endpoint and found that nVNS outperformed sham device treatment in yielding pain freedom through 30, 60, and 120 minutes.

Notably, the pain-free responder rate of 30.4% at 120 minutes in those receiving nVNS was similar to that seen in previous research assessing the efficacy of oral triptans and potent nonsteroidal anti-inflammatory drugs.

The team did not observe significant results secondary to sham device treatment.

In patients treated with nVNS, the most common adverse events were application site discomfort and nasopharyngitis. No serious adverse events were reported. Only two patients discontinued the study due to adverse events, and both were in the sham control group.

According to the authors, these findings “strongly suggest that nVNS is effective and has benefits consistent with standard drug options but with the added benefit of an extremely benign adverse effect profile and the flexibility to be used for multiple attacks without the risk of medication overuse or drug-related adverse effects.”

One limitation of the current study was the selection of an appropriate sham therapy device. As recommended in the literature, the sham device in the current study had an active signal that could be perceived by the subject, but the signal did not stimulate the vagus nerve.

In accompanying commentary also published in Neurology, outside experts provided perspective on the findings of the PRESTO trial.

“These approaches are particularly useful in patients who prefer nonpharmacologic options, in those with medication overuse, and in those who do not respond to or have side effects from pharmacotherapy,” wrote Richard B. Lipton, MD, professor and vice chair, Department of Neurology, the Edwin S. Lowe Chair in Neurology, Albert Einstein College of Medicine, Bronx, NY, and director, Montefiore Headache Center. “They are often a useful adjunct to pharmacotherapy. At the moment, access to these treatments is limited by reimbursement.”

This study was funded by electroCore, LLC.