Cluster headache

Last updated: November 20, 2023

Summarytoggle arrow icon

Cluster headache (CH) is a type of primary headache that mostly affects adult men. Patients present with recurrent attacks of agonizing, strictly unilateral headaches in the periorbital and forehead region (areas innervated by the trigeminal nerve) that last from fifteen minutes up to three hours. These attacks are associated with ipsilateral symptoms of increased cranial autonomic activity, e.g., lacrimation, conjunctival injection, rhinorrhea, or partial Horner syndrome. Cluster headaches tend to occur in episodic patterns (called cluster periods or cluster bouts) followed by months of remission; they are considered chronic if remission between bouts lasts less than three months. Diagnosis is based on the patient's history, in particular on the exact description and timing of the headaches. In patients with red flag symptoms for headache, secondary headache should be ruled out using an MRI. Acute episodes are treated with 100% oxygen and/or triptans, and verapamil is most commonly used as prophylaxis.

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

The etiology of cluster headache is not entirely understood but is thought to involve a genetic component.

Clinical featurestoggle arrow icon

  • Headache characteristics
    • Agonizing pain
    • Strictly unilateral, periorbital, and/or temporal
    • Quickly developing (within minutes), short, recurring attacks; that usually occur in a cyclical pattern (“cluster periods”)
      • May become chronic (less common), with interruptions of less than three months between cluster bouts [2]
      • Attacks often wake patients up during sleep.
  • Ipsilateral autonomic symptoms
  • Restlessness and agitation

While patients with migraine headaches tend to rest motionlessly in a quiet, dark room, individuals with cluster headache pace around restlessly in excruciating pain!


Diagnosticstoggle arrow icon

Approach [1][9]

In patients with high-risk headaches, obtain further diagnostics to rule out life-threatening secondary headaches (e.g., SAH, meningitis).

Diagnostic criteria [2]

Diagnostic criteria for cluster headache

A diagnosis of cluster headache can be established in the presence of ≥ 5 attacks that fulfill criteria 1–4.

  1. Severe unilateral, orbital, supraorbital, and/or temporal pain for a duration of 15–180 minutes (if untreated)
  2. At least one of the following:
  3. Frequency: from 1 every other day to 8 per day
  4. Not better explained by another diagnosis


  • Episodic cluster headache
    • ≥ 2 cluster periods lasting 7 days to 1 year
    • Remission periods (i.e., pain-free periods) of ≥ 3 months
  • Chronic cluster headache
    • Cluster periods for ≥ 1 year
    • Remission periods of < 3 months, or no remission

Differential diagnosestoggle arrow icon

See the article on “Headache for more information regarding differential diagnoses.

Paroxysmal hemicrania

Short-lasting unilateral neuralgiform headache attacks

References: [2][12][13][14][15]

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

Approach [9][16]

Acute treatment [1][16][17]

Standard analgesics (e.g., acetaminophen, NSAIDs, opioids) are not recommended because they are ineffective and may lead to medication overuse headache if used frequently. [19]

To improve absorption, apply nasal sprays in the nostril unaffected by congestion.

Prophylactic treatment [9][16][20][21]

Transitional therapy with shorter onset latencies may be necessary until prophylactic treatment takes effect.

Neuromodulation [1][9][16]

Neuromodulation is usually reserved for cluster headache refractory to multiple medical treatments.

  • Noninvasive neurostimulation: noninvasive vagus nerve stimulation [9]
  • Invasive neurostimulation: e.g., sphenopalatine ganglion stimulation and occipital nerve stimulation [1][16]
    • Disadvantages: uncertain benefits, potential for serious adverse effects
    • Advantages: possible acute and prophylactic effects

Acute management checklisttoggle arrow icon

Referencestoggle arrow icon

  1. May A, Schwedt TJ, Magis D, Pozo-Rosich P, Evers S, Wang S-J. Cluster headache. Nat Rev Dis Primers. 2018; 4 (1).doi: 10.1038/nrdp.2018.6 . | Open in Read by QxMD
  2. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38 (1): p.1-211.doi: 10.1177/0333102417738202 . | Open in Read by QxMD
  3. Ferrari A, Zappaterra M, Righi F, et al. Impact of continuing or quitting smoking on episodic cluster headache: a pilot survey. J Headache Pain. 2013; 14 (1).doi: 10.1186/1129-2377-14-48 . | Open in Read by QxMD
  4. Costa A, Antonaci F, Ramusino M, Nappi G. The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias. Curr Neuropharmacol. 2015; 13 (3): p.304-323.doi: 10.2174/1570159x13666150309233556 . | Open in Read by QxMD
  5. Clinical Reasoning: Partial Horner syndrome and upper right limb symptoms following chiropractic manipulation. Updated: May 26, 2015. Accessed: April 2, 2017.
  6. Matharu M. Cluster Headache. BMJ Clin Evid. 2010; 2010 (1212).
  7. Mendizabal JE, Umaña E, Zweifler RM. Cluster headache: Horton's cephalalgia revisited. South Med J. 1998; 91 (7): p.606-617.
  8. Weintraub JR. Cluster headaches and sleep disorders. Curr Pain Headache Rep. 2003; 7 (2): p.150-156.
  9. Cittadini E, Matharu MS, Goadsby PJ. Paroxysmal hemicrania: a prospective clinical study of 31 cases. Brain. 2008; 131 (4): p.1142-1155.doi: 10.1093/brain/awn010 . | Open in Read by QxMD
  10. Alternatives in drug treatment of chronic paroxysmal hemicrania. Updated: July 1, 1996. Accessed: April 2, 2017.
  11. Short-Lasting Unilateral Neuralgiform Headache With Conjunctival Injection and Tearing (SUNCT). Updated: April 1, 2020. Accessed: May 12, 2020.
  12. Pareja JA, Álvarez M, Montojo T. SUNCT and SUNA: Recognition and Treatment. Curr Treat Options Neurol. 2012; 15 (1): p.28-39.doi: 10.1007/s11940-012-0211-8 . | Open in Read by QxMD
  13. International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013; 33 (9): p.629-808.doi: 10.1177/0333102413485658 . | Open in Read by QxMD
  14. Robbins MS, Starling AJ, Pringsheim TM, Becker WJ, Schwedt TJ. Treatment of Cluster Headache: The American Headache Society Evidence-Based Guidelines. Headache. 2016; 56 (7): p.1093-1106.doi: 10.1111/head.12866 . | Open in Read by QxMD
  15. Malu OO, Bailey J, Hawks MK. Cluster Headache: Rapid Evidence Review. Am Fam Physician. 2022; 105 (1): p.24-32.
  16. Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharmacologic treatment of cluster headache. Neurology. 2010; 75 (5): p.463-473.doi: 10.1212/wnl.0b013e3181eb58c8 . | Open in Read by QxMD
  17. Weaver-Agostoni J. Cluster headache.. Am Fam Physician. 2013; 88 (2): p.122-8.
  18. Paemeleire K, Evers S, Goadsby PJ. Medication-overuse headache in patients with cluster headache. Curr Pain Headache Rep. 2008; 12 (2): p.122-127.doi: 10.1007/s11916-008-0023-4 . | Open in Read by QxMD
  19. Brandt RB, Doesborg PGG, Haan J, Ferrari MD, Fronczek R. Pharmacotherapy for Cluster Headache. CNS Drugs. 2020; 34 (2): p.171-184.doi: 10.1007/s40263-019-00696-2 . | Open in Read by QxMD
  20. May A, Leone M, Áfra J, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol. 2006; 13 (10): p.1066-1077.doi: 10.1111/j.1468-1331.2006.01566.x . | Open in Read by QxMD
  21. Whitehead MT, Cardenas AM, Corey AS, et al. American College of Radiology ACR Appropriateness Criteria® Headache. J Am Coll Radiol. 2019.doi: 10.1016/j.jacr.2019.05.030 . | Open in Read by QxMD
  22. Mazzoni P, Pearson T, Rowland LP. Merritt's Neurology Handbook. Lippincott Williams & Wilkins ; 2006
  23. Cluster Headache. Updated: January 1, 2017. Accessed: April 2, 2017.
  24. Blanda M. Cluster Headache: Treatment & Management. Cluster Headache: Treatment & Management. New York, NY: WebMD. Updated: January 12, 2017. Accessed: April 2, 2017.
  25. Goadsby PJ. Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol. 2002; 1 (4): p.251-257.
  26. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
  27. Matharu MS, Levy MJ, Meeran K, Goadsby PJ. Subcutaneous octreotide in cluster headache: Randomized placebo-controlled double-blind crossover study. Ann Neurol. 2004; 56 (4): p.488-494.doi: 10.1002/ana.20210 . | Open in Read by QxMD
  28. Ferri FF. Ferri's Clinical Advisor 2015 E-Book. Elsevier Health Sciences ; 2014
  29. Levine H. Headache in Otolaryngology: Rhinogenic and Beyond, An Issue of Otolaryngologic Clinics of North America,. Elsevier Health Sciences ; 2014
  30. Goadsby PJ, Dodick DW, Leone M, et al. Trial of Galcanezumab in Prevention of Episodic Cluster Headache. N Engl J Med. 2019; 381 (2): p.132-141.doi: 10.1056/nejmoa1813440 . | Open in Read by QxMD

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