By Louise M. Klebanoff, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Klebanoff reports no financial relationships relevant to this field of study.

SYNOPSIS: Trigeminal autonomic cephalgias are notoriously difficult to treat and may be responsive to noninvasive vagus nerve stimulation.

SOURCE: Tso AR, et al. Research letter: Noninvasive vagus nerve stimulation for treatment of indomethacin-sensitive headaches. JAMA Neurol 2017;74:1266-1267.

Trigeminal autonomic cephalgias (TACs) are primary headache disorders characterized by unilateral pain and associated ipsilateral autonomic symptoms, including ptosis, periorbital edema, conjunctival injection, lacrimation, nasal congestion, and rhinorrhea. TACs include cluster headache, paroxysmal hemicrania (PH), hemicrania continua (HC), and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. The duration of individual attacks and the number of attacks that occur daily help distinguish these specific syndromes. PH, with attacks lasting two to 30 minutes and occurring several times a day, and HC, with exacerbations of continuous pain lasting hours or days at a time, also are distinguished by their response to indomethacin. Unfortunately, the high doses of indomethacin sometimes required for pain relief often are tolerated poorly because of gastrointestinal side effects.

Transcutaneous stimulation of the vagus nerve with the gammaCore device has been shown to be effective for the acute treatment of episodic cluster headache. The authors postulated that vagus nerve stimulation also could be useful in PH and HC. Through record review, the authors identified 15 patients with HC (9) and PH (6) who used noninvasive vagus nerve stimulation as either primary treatment (10 patients) or adjuvant treatment (five patients) who continued to take oral indomethacin. GammaCore generates a 120-second electrical impulse of adjustable amplitude that stimulates the vagus nerve when held against the neck. Patients were advised to begin with two 120-second impulses applied ipsilateral to the pain twice daily, titrating up as needed and as tolerated. The doses used ranged from two to four doses twice daily to two or three doses three times a day. The duration of use varied from three months to five years.

Among patients with HC, seven (78%) reported reduced pain severity; two reported reduced frequency of exacerbations; and one reported reduced duration of exacerbations. Among patients with PH, four (67%) reported benefit of treatment; one became attack-free; two reported reduced attack frequency; three reported reduced severity; and one reported shorter duration of attacks. Only one patient needed to reduce the dose of the stimulator because of cutaneous irritation.


This retrospective study of 15 patients with either PH or HC reviewed the potential benefit of noninvasive vagus nerve stimulation for indomethacin-sensitive headaches. Although only one patient became attack-free with treatment, a majority of patients reported benefit in reduction of attack severity, frequency, or duration. Gastrointestinal side effects often limit the usefulness of indomethacin to treat these primary headache syndromes; non-invasive vagus nerve stimulation tends to be well-tolerated, with only one of 15 patients developing cutaneous irritation. As the authors cited, two randomized trials have shown the benefit of vagus nerve stimulation in cluster headache, another type of TAC. This study provides rationale for a prospective, randomized, sham-controlled trial in the use of vagus nerve stimulation in PH and HC.