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Clinical Review State of the Art Review

Recent advances in the diagnosis and management of cluster headache

BMJ 2022; 376 doi: (Published 16 March 2022) Cite this as: BMJ 2022;376:e059577
  1. Emmanuelle A D Schindler, assistant professor1 2,
  2. Mark J Burish, assistant professor3
  1. 1Department of Neurology, Yale University School of Medicine, New Haven, CT, USA
  2. 2Veterans Health Administration Headache Center of Excellence, Veterans Affairs Connecticut Healthcare System, West Haven, CT
  3. 3Department of Neurosurgery, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA
  1. Correspondence to: M J Burish mark.j.burish{at}


Cluster headache, a primary headache disorder, consists of short (15-180 minutes), frequent (up to eight a day), unilateral attacks of facial pain with associated ipsilateral autonomic features and restlessness. The attacks are suspected to be one of the most painful human experiences, and the disorder is associated with a high rate of suicidal ideation. Proper diagnosis is key, as some of the most effective treatments, such as high flow oxygen gas, are rarely used in other headache disorders. Yet diagnostic delay is typically years for this disorder, as it is often confused with migraine and trigeminal neuralgia, and secondary causes may be overlooked. This review covers the clinical, pathophysiologic, and therapeutic features of cluster headache. Recent updates in diagnosis include the redefinition of chronic cluster headache (remission periods lasting less than three months instead of the previous one month), and recent advances in management include new treatments for episodic cluster headache (galcanezumab and non-invasive vagus nerve stimulation).


  • Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

  • Contributors: EADS and MJB both did the literature search. Both authors were substantially involved in the conception, initial drafting, and editing of the manuscript. Both authors have given final approval of the manuscript. MJB is the guarantor.

  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: EADS previously received research funding from Clusterbusters for research on oxygen in cluster headache, receives research funding from Ceruvia (previously through Heffter Research Institute) for her clinical trial of psilocybin in cluster headache, receives research funding from the Wallace Research Foundation for work unrelated to cluster headache, anticipates receiving additional research funding from Ceruvia for cluster headache research in the next 12 months, and is an unpaid member of the medical advisory board of Clusterbusters and Ceruvia; MJB was a paid consultant for the American Headache Society in presenting material for its 2020 annual meeting, was an unpaid medical adviser for Praxis Precision Medicines (in lieu of compensation a fee was paid to the University of Texas Health Science Center at Houston), and was an unpaid consultant for Beckley Psytech Ltd (in lieu of compensation a donation was made to the Will Erwin Headache Research Foundation); his roles as adviser and consultant were not related to cluster headache; additionally, he is employed by the University of Texas Health Science Center at Houston, receives research funding from the Will Erwin Headache Research Foundation, is an unpaid member of the medical advisory board of Clusterbusters, and is a site investigator for a clinical trial in cluster headache funded by Lundbeck.

  • Patient involvement: The video of a patient with a cluster headache attack was made specifically for this article.

  • Provenance and peer review: Commissioned; externally peer reviewed.

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