Cluster headache is one of the most severe types of headache known. Patients describe the pain as the worst they have ever experienced. It is rare, affecting about one in a thousand people in the population. The mean age at onset is 30. It is more common in men than in women. Older studies reported a male-to-female ratio of four to one, while recent studies have found it to be two to one. One reason for this is that the diagnosis is missed more often in women.
The pain is one-sided. It is located around the eye, above the eyebrow, or in the temple. An attack lasts 15 to 180 minutes and can recur up to eight times a day. Most patients have two attacks a day. Attacks often begin at night, waking the patient from sleep, and at about the same time every day. Autonomic symptoms accompany the pain on the affected side. These are tearing or redness of the eye (90 percent of patients), nasal congestion or discharge (84 percent), swelling of the eyelid, drooping of the eyelid, and constriction of the pupil. A patient with migraine lies still in a dark room. A patient with cluster headache cannot stay still. They pace, or rock back and forth.
Attacks come in cluster periods. In the episodic form, a cluster period lasts 7 days to 1 year and is separated by pain-free periods of at least three months. Between 85 and 90 percent of patients are in this group. In the chronic form, there is no pain-free period, or it is shorter than three months. Patients usually have one or two periods a year. These periods most often begin in spring and autumn. During a period, alcohol triggers attacks. Nitroglycerin, hot weather, high altitude, stress, and changes in sleep pattern can also be triggers. Most patients smoke. Quitting smoking has not been shown to reduce the number of attacks, but it is still recommended.
The cause of the disease is not fully known. The circadian and seasonal pattern of the attacks has suggested that the hypothalamus plays a role. PET studies have detected activation in the hypothalamus during an attack. Patients have low melatonin levels. The trigeminovascular system and the trigeminal autonomic reflex are responsible for the pain. During an attack, the levels of neuropeptides such as CGRP and PACAP-38 rise. There is also a genetic predisposition. The risk of the disease is high in first-degree relatives. Genome-wide studies have identified four gene regions that increase the risk.
The diagnosis is made clinically. At least five attacks are required, and the attacks are expected to have the features described above. The average diagnostic delay is five years. The disease is often diagnosed as sinusitis or migraine, and ineffective treatments such as nasal decongestants may be given. Brain MRI may be needed to rule out structural causes.
The most effective treatment during an attack is 100 percent oxygen. It is given at 7 to 12 liters per minute through a non-rebreathing face mask and continued for 15 to 30 minutes. At least two thirds of patients respond. The effect often begins in less than 10 minutes. Oxygen has no serious side effects. Subcutaneous sumatriptan 6 mg is the second choice, with a maximum of 12 mg in 24 hours. In patients who cannot tolerate injections, sumatriptan or zolmitriptan nasal spray can be tried. Oral triptans are not recommended for attack treatment because their effect begins late. Non-invasive vagus nerve stimulation is also one of the options for attack treatment in the episodic form.
Preventive drugs take a few weeks to start working. During this time, corticosteroids can be used as transitional treatment. Prednisone is given as 100 mg once daily for five days, and the dose is then reduced by 20 mg every three days. An injection of a corticosteroid and a local anesthetic into the greater occipital nerve is also used for the same purpose. Its effect lasts weeks to months.
Verapamil is the first choice for preventive treatment. It is started at 80 mg three times a day, and the dose can be increased gradually up to 960 mg per day. Fifty to 80 percent of patients respond. At high doses, PR prolongation, heart block, and bradycardia can occur. If verapamil is insufficient or not tolerated, lithium, topiramate, and melatonin can be used. Lithium has a narrow therapeutic range, and its blood level must be monitored.
Galcanezumab, a monoclonal antibody against CGRP, has been found effective in episodic cluster headache. Studies in the chronic form have not shown benefit. According to reviews from 2025, galcanezumab is approved only in the United States, and only for episodic cluster headache.
Some patients with chronic cluster headache do not respond to medication. In these patients, occipital nerve stimulation, sphenopalatine ganglion stimulation, and deep brain stimulation directed at the hypothalamus can be tried.
References
Kandel SA, Mandiga P. Cluster Headache. StatPearls. 2023.
Lansbergen CS, et al. Cluster Headache. Pain Pract. 2025;25:e70050.
de Freitas Dias B, et al. Current and Novel Therapies for Cluster Headache: A Narrative Review. Pain Ther. 2025;14:1-19.
Goadsby PJ, et al. Trial of Galcanezumab in Prevention of Episodic Cluster Headache. N Engl J Med. 2019;381:132-141.
