Treating Cluster Headache: Weighing Current Therapies

Self injection in leg
Self injection in leg
The 2 treatments for cluster headache with Level A recommendations are either not readily accessible via public or private insurance or are not recommended in a large subset of patients with cardiovascular disease.

Of the various identified types of headache, cluster headache (CH) is considered the most severe and the most difficult to treat. In 2016, the American Headache Society (AHS) released new evidence-based guidelines for the treatment of CH.1 Treatments are categorized as acute/abortive, preventative, and transitional. They overlap, with short-term strategies aimed at aborting current attacks by any means possible while using a longer-term approach to reduce the frequency of future attack clusters. Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine and director of the Dartmouth Headache Center in Lebanon, New Hampshire, explained to Neurology Advisor: “In cluster, patients require prevention and they require acute treatment. Cluster is an emergency.”

Abortive Treatment

The 2016 AHS guidelines1 still only include 2 Level A recommendations for acute treatment in CH: high flow oxygen and subcutanteous sumatriptan injections (subQ). Inhaled oxygen is highly (60% to 70%) effective in aborting attacks, although due to a decision by the United States (US) Centers for Medicaid and Medicare Services (CMS) to not to cover it under CMS insurance, it is not readily accessible to many patients.2-4

Sumatriptan subQ remains the gold standard in cluster headache treatment in the United States; however, due to warnings against the use of triptans in patients with cardiovascular risk factors, these drugs are not recommended in many patients with cluster headache.5-7

“How you manage an acute attack depends on a number of small factors, including the number of events you are having per day,” Brian E. McGeeney, MD, MPH, MBA, assistant professor of neurology at Boston University School of Medicine in Massachusetts, told Neurology Advisor. “There are plenty of people who have 1-2 attacks per day in a cycle, and then there are others who have 5-6. You can’t use the injections that frequently, and oxygen becomes much more important then,” he said.

Other acute options include a nasal formulation of zolmitriptan. “That’s probably the next best of the pharmaceutical agents, although that’s still not as good as sumatriptan injectable and has potentially the same side-effect profile,” Dr McGeeney explained, noting also the use of nasal ketamine, a schedule 3 agent, in exceptional circumstances. “It can work quickly for those who know how to use it — but that’s not a first line agent – it’s for [patients] who have failed other agents. There’s also nasal lidocaine, though it’s less common. I don’t believe it works well, but it’s certainly well tolerated and can be given to people with vascular disease.”

In addition, sphenopalatine ganglion stimulation (SGS) was given a Level B recommendation, based on the addition of a single study demonstrating a 67% reduction in acute attack at 15 minutes compared with 7% in a sham group.8 

The newest treatment for acute CH is a vagus nerve stimulator, reported Matthew S. Robbins, MD, FAAN, FAHS, chief of neurology at the Jack D. Weiler Hospital at Montefiore Medical Center and director of inpatient services at the Montefiore Headache Center in New York, New York, who coauthored the 2016 guidelines. “The evidence suggests that it works for people with episodic cluster headache, although it is quite an expensive device to use,” Dr Robbins said. Dr McGeeney was less convinced of its efficacy. “The FDA [US Food and Drug Administration] recently approved a noninvasive handheld vagal stimulator — a neat looking device — and it’s being marketed as an abortive agent for cluster; however, the data is very poor. I’m very disappointed by it,” he said.

Prophylactic and Transitional Treatment

Previously, no Level A prophylactic recommendations existed, despite numerous therapies.1 “The reason for that is that many of the medicines are very old and they don’t have the support from a pharmaceutical company to study and lead to high quality evidence,” Dr Robbins explained. “Guidelines from other countries that don’t just go by level of evidence, and that factor in expert opinions, give high-level recommendations for verapamil and also lithium. Those are the two most successful preventative medicines for cluster headache available right now.”

According to the guidelines, verapamil and lithium (Level C) are considered maintenance therapies. 1 Suboccipital steroid injections were added with Level A recommendations for the transitional prophylactic treatment of cluster headache. “We often use short-term preventative therapies like an occipital nerve injection with a steroid, or a course of an oral steroid to break people out of a cycle. Those are generally pretty successful,” Dr Robbins said. “They’re used because the preventative medicines like verapamil can take a week or longer to kick in, so we use one of these other therapies as a bridge until the other therapies start working.”

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“Everyone is going to be offered prophylactic therapy, although plenty of patients don’t want it because of the high failure rate of prophylactic therapies,” said Dr McGeeney. “There are plenty of patients who have decoupled from the medical community, because while managed medically, they’re in the same amount of pain, plus have gut disturbances from the pharmaceuticals, and they don’t see the benefit. They often use oxygen and that’s it.”

“You really have to try to optimize preventative treatment,” Dr Robbins said. “The vagal nerve stimulator would be a good option for those people who can’t take other therapies, because it seems safe and is generally without very many contraindications, but it is expensive.”

Future Outlook

“I think patients with episodic cluster headache can generally be managed pretty well using our existing medicines,” Dr Robbins said. “We can make a substantial improvement and shorten their cluster headache cycle effectively. The people with chronic cluster headache — which makes up about 10% — are typically less responsive to many of these treatments, although they still respond to oxygen just as well as others.”

He pointed to calcitonin gene-related peptide (CGRP)-based treatments currently be studied for migraine that may have promise in cluster headache. “They’re going to be preventative as well,” he said, “but again, those are going to be expensive therapies.”


  1. Robbins MS, Starling AF, Pringshein TM, Becker WJ, Schwedt TJ. Treatment of cluster headache: The American Headache Society Evidence-Based Guidelines. Headache. 2016;56:1093-1096.
  2. Tepper SJ, Duplin J, Nye B, Tepper DE. Prescribing oxygen for cluster headache: a guide for the provider [published online August 30, 2017]. Headache. doi:10.1111/head.13180
  3. National coverage determination (NCD) for home oxygen use to treat cluster headache (CH) (240.2.2). Centers for Medicare & Medicaid Services website. Updated January 4, 2011. Accessed September 20, 2017.
  4. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache. JAMA. 2009;302:2451-2457.
  5. Leone M, Giustiniani A, Cecchini AP. Cluster headache: present and future therapy. Neurol Sci. 2017;38(1):45-50.
  6. The Sumatriptan Cluster Headache Study Group. Treatment of acute cluster headache with sumatriptan. N Engl J Med. 1991;325:322-326.
  7. Ekbom K, Monstad I, Prusinski A et al. Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose-comparison study. The Sumatriptan Cluster Headache Study Group. Acta Neurol Scand. 1993;88:63-69.
  8. Schoenen J, Jensen RH, Lanteri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: A randomized, sham-controlled study. Cephalalgia. 2013;33:816-830.