Definition

International Classification of Headache Disorders (ICHD-3) diagnostic criteria for cluster headache:

A. At least five attacks fulfilling criteria B-D

B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes (when untreated)1

C. Either or both of the following:

  1. at least one of the following symptoms or signs, ipsilateral to the headache:
    • conjunctival injection and/or lacrimation
    • nasal congestion and/or rhinorrhoea
    • eyelid oedema
    • forehead and facial sweating
    • miosis and/or ptosis
  2. a sense of restlessness or agitation

D. Occurring with a frequency between one every other day and 8 per day2

E. Not better accounted for by another ICHD-3 diagnosis.


1 During part, but less than half of the active time course of cluster headache, attacks may be less severe and/or of shorter or longer duration. 2 During part, but less than half of the active time course of cluster headache, attacks may be less frequent.

ICHD-3 diagnostic criteria for episodic cluster headache:

A. Attacks fulfilling criteria cluster headache and occurring in bouts (cluster periods)

B. At least two cluster periods lasting from 7 days to 1 year (when untreated) and separated by pain-free remission periods of ≥3 months.


Cluster periods usually last between 2 weeks and 3 months.

ICHD-3 diagnostic criteria for chronic cluster headache:

A. Attacks fulfilling criteria for cluster headache

B. Occurring without a remission period, or with remissions lasting <3 months, for at least 1 year.


Chronic cluster headache may arise de novo (previously referred to as primary chronic cluster headache), or evolve from episodic cluster headache (previously referred to as secondary chronic cluster headache). In some patients change occurs from chronic cluster headache to episodic cluster headache.

Cluster headache characteristics

  • About 85-90% of patients have episodic cluster headache. Attacks occur in clusters lasting for weeks or months separated by remission periods lasting months or years.
  • About 10-15% of patients have chronic cluster headache, without such remission periods.
  • During a cluster period and at any time in chronic cluster headache, attacks occur regularly and may be precipitated by alcohol, histamine, nitroglycerine, stress, glare and sexual activity.
  • Age at onset is usually 20-40 years and men are affected three times more often than women.
  • Some patients have both cluster headache and trigeminal neuralgia, sometimes referred to as cluster-tic syndrome. Both must be treated for the patient to become headache-free.
  • The attacks usually last between 15 minutes to 3 hours. They may occur up to 8 times per day, most commonly twice, usually at night.
  • Photophobia and phonophobia, if present, are usually ipsilateral, contrary to migraine where they are always bilateral.
  • Up to one third of patients may experience general allodynia, more commonly women, patients with recent attacks, and patients with young age at onset.
  • Suicidal ideation associated with the attacks is not uncommon but the risk of suicide is low.

Evaluation

The diagnosis is clinical. It is essential to rule-out secondary causes of headache (see Red flags in headache diagnosis). Neuroimaging, prefferably with MRI should be considered to rule out structural abnormalities (vascular malformations, tumors including pituitary adenomas and inflammatory lesions have all been described as causes for cluster headache). Atypical features, abnormal neurologic status and late age at onset should always heighten the suspicion for a secondary cause.


Treatment

A. Acute (abortive) treatment.

Aims to terminate an ongoing bout of headache.


  1. 100% oxygen 12-15L via nonrebreather mask will terminate an attack in about 60% of patients, usually within 10 minutes
  2. Triptans
    • Sumatriptan 3, 4 or 6 mg SC
    • Sumatriptan 20 mg IN
    • Zolmitriptan 5-10 mg IN
  3. Lidocaine
    • 4% administered IN ipsilateral to the pain
  4. Nasal ketamine
    • May be helpful in aborting an attack but data is very limited

B. Transitional treatment

Used as a bridge to reduce cluster headache attack frequency while patients wait for preventive regimens to take effect.


  1. Prednisone 100 mg p.o. tapering by 20 mg every 2-3 days

C. Preventive treatment

Used to reduce the frequency of cluster headache attack.


  1. Verapamil
    • Start at 80 mg three times daily, titrate by 80 mg every 2 weeks to effect
    • Do not exceed 960 mg total daily dose
    • Caution for PR prolongation and AV block
  2. Lithium 600 and 1500 mg daily p.o.
  3. Antiepileptics
    • Topiramate 100-150 mg p.o.
    • Gabapentin 1000-1800 mg p.o.
    • Valproate 600-2000 mg p.o. (weak evidence of efficacy)
  4. Galcanezumab 120 mg SC monthly (for episodic cluster headache)
  5. Melatonin 10 mg p.o.
  6. Occipital nerve blockade with corticosteroids ± local anesthesia
  7. Vagus nerve stimulation
  8. Deep brain stimulation

References

  • Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211
  • Cluster headache: A review of clinical presentation, evaluation, and management JAAPA. 2022 Aug 1;35(8):15-19. doi: 10.1097/01.JAA.0000840484.33065.21
  • Cluster headache due to structural lesions: A systematic review of published cases. World J Clin Cases. 2021 May 16;9(14):3294-3307 doi: 10.12998/wjcc.v9.i14.3294
  • Drug Treatment of Cluster Headache Drugs. 2021 Dec 17;82(1):33–42. doi: 10.1007/s40265-021-01658-z
  • Treatment of Cluster Headache: The American Headache Society Evidence-Based Guidelines Headache. 2016 Jul;56(7):1093-106 doi: 10.1111/head.12866
  • Preventive treatment of refractory chronic cluster headache: systematic review and meta-analysis J Neurol . 2023 Feb;270(2):689-710. doi: 10.1007/s00415-022-11436-w
  • DBS for chronic cluster headache: meta‐analysis of individual patient data. Annals of Neurology. doi: 10.1002/ana.25887
  • EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias Eur J Neurol . 2006 Oct;13(10):1066-77. doi: 10.1111/j.1468-1331.2006.01566.x