Which Treatments Are Effective Against Intractable Cluster Headache?

Preventive Treatment Is Essential

“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.

Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.

Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.

Other Treatments May Be Effective

The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.

Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.

Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.

Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.

—Erik Greb

Suggested Reading

Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.

Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.

Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.

Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.

Schoenen J, Jensen RH, Lantéri-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(10):816-830.