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Cluster headache

Cluster headache is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s).[1] There is often accompanying eye watering, nasal congestion, or swelling around the eye on the affected side.[1] These symptoms typically last 15 minutes to 3 hours.[2] Attacks often occur in clusters which typically last for weeks or months and occasionally more than a year.[2]

Cluster headache

Recurrent, severe headaches on one side of the head, eye watering, stuffy nose[1]

20 to 40 years old[2]

15 min to 3 hrs[2]

Episodic, chronic[2]

Unknown[2]

Tobacco smoke, family history[2]

Based on symptoms[2]

~0.1% at some point in time[5]

The cause is unknown,[2] but is most likely related to dysfunction of the posterior hypothalamus.[6] Risk factors include a history of exposure to tobacco smoke and a family history of the condition.[2] Exposures which may trigger attacks include alcohol, nitroglycerin, and histamine.[2] They are a primary headache disorder of the trigeminal autonomic cephalalgias type.[2] Diagnosis is based on symptoms.[2]


Recommended management includes lifestyle adaptations such as avoiding potential triggers.[2] Treatments for acute attacks include oxygen or a fast-acting triptan.[2][4] Measures recommended to decrease the frequency of attacks include steroid injections, galcanezumab, civamide, verapamil, or oral glucocorticoids such as prednisone.[6][4][7] Nerve stimulation or surgery may occasionally be used if other measures are not effective.[2][6]


The condition affects about 0.1% of the general population at some point in their life and 0.05% in any given year.[5] The condition usually first occurs between 20 and 40 years of age.[2] Men are affected about four times more often than women.[5] Cluster headaches are named for the occurrence of groups of headache attacks (clusters).[1] They have also been referred to as "suicide headaches".[2]

is a unilateral headache condition, without the male predominance usually seen in cluster headaches. Paroxysmal hemicrania may also be episodic but the episodes of pain seen in chronic paroxysmal hemicrania are usually shorter than those seen with cluster headaches. Chronic paroxysmal hemicrania typically responds "absolutely" to treatment with the anti-inflammatory drug indomethacin[21] where in most cases cluster headaches typically show no indomethacin response, making "indomethacin response" an important diagnostic tool for specialist practitioners seeking correct differential diagnosis between the conditions.[43][44]

Chronic paroxysmal hemicrania

[45]

Hemicrania continua

is a headache syndrome belonging to the group of TACs.[21][46]

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)

is a unilateral headache syndrome,[40] or "cluster-like" headache.[47]

Trigeminal neuralgia

Epidemiology[edit]

Cluster headache affects about 0.1% of the general population at some point in their life.[5] Males are affected about four times more often than females.[5] The condition usually starts between the ages of 20 and 50 years, although it can occur at any age.[1] About one in five of adults reports the onset of cluster headache between 10 and 19 years.[67]

Society and culture[edit]

Robert Shapiro, a professor of neurology, says that while cluster headaches are about as common as multiple sclerosis with a similar disability level, as of 2013, the US National Institutes of Health had spent $1.872 billion on research into multiple sclerosis in one decade, but less than $2 million on cluster headache research in 25 years.[74]

Research directions[edit]

Some case reports suggest that ingesting tryptamines such as LSD, psilocybin (as found in hallucinogenic mushrooms), or DMT can abort attacks and interrupt cluster headache cycles.[75][76] The hallucinogen DMT has a chemical structure that is similar to the triptan sumatriptan, indicating a possible shared mechanism in preventing or stopping migraine and TACs.[51] In a 2006 survey of 53 individuals, 18 of 19 psilocybin users reported extended remission periods. The survey was not a blinded or a controlled study, and was "limited by recall and selection bias".[75] The safety and efficacy of psilocybin is currently being studied in cluster headache, with the extension phase of one randomized controlled trial demonstrating reduced cluster attack burden after a 3-dose pulse of psilocybin.[77][78][79]


Fremanezumab, a humanized monoclonal antibody directed against calcitonin gene-related peptides alpha and beta, was in phase 3 clinical trials for cluster headaches, but the studies were stopped early due to a futility analysis demonstrating that a successful outcome was unlikely.[80][81]