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Cluster Headache


Stephen D. Silberstein

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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Cluster headaches cause excruciating, unilateral periorbital or temporal pain, with ipsilateral autonomic symptoms (ptosis, lacrimation, rhinorrhea, nasal congestion). Diagnosis is clinical. Acute treatment is with parenteral triptans, dihydroergotamine, or oxygen. Prevention is with verapamil, lithium, topiramate, divalproex, galcanezumab (a monoclonal antibody), or a combination.

Cluster headache affects primarily men, typically beginning at age 20 to 40; prevalence in the US is 0.4%. Usually, cluster headache is episodic; for 1 to 3 months, patients experience 1 attack/day, followed by remission for months to years. Some patients have cluster headaches without remission.

Pathophysiology is unknown, but the periodicity suggests hypothalamic dysfunction.

Alcohol intake triggers cluster headache during the attack period but not during remission.

Symptoms and Signs of Cluster Headache

Symptoms of cluster headache are distinctive. Attacks, often multiple, frequently occur at the same time each day, often awakening patients from sleep.

When attacks occur, pain is always unilateral and occurs on the same side of the head in an orbitotemporal distribution. It is excruciating, peaking within minutes; it usually subsides spontaneously within 30 minutes to 1 hour. Patients are agitated, restlessly pacing the floor, unlike migraine patients who prefer to lie quietly in a darkened room. The restlessness can be so severe that it leads to bizarre behavior (eg, banging the head on a wall).

Autonomic features, including nasal congestion, rhinorrhea, lacrimation, facial flushing, and Horner syndrome, are prominent and occur on the same side as the headache.

Diagnosis of Cluster Headache

  • Clinical evaluation

Diagnosis of cluster headache is based on the distinctive symptom pattern and exclusion of intracranial abnormalities.

Other unilateral primary headache syndromes with autonomic symptoms, which are sometimes grouped together with cluster headache as trigeminal autonomic cephalgias, should be excluded:

  • SUNCT (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing): Attacks are very brief (5 to 250 seconds) and occur at high frequency (up to 200 attacks/day).

  • Chronic paroxysmal hemicrania: Attacks are more frequent (> 5/day) and much briefer (usually just minutes) than in cluster headache.

  • Hemicrania continua: Moderately severe continuous unilateral head pain occurs with superimposed brief episodes of more intense pain.

Chronic paroxysmal hemicrania and hemicrania continua, unlike SUNCT and cluster headache (and migraine), respond dramatically to indomethacin, but not to other nonsteroidal anti-inflammatory drugs (NSAIDs).

Treatment of Cluster Headache

  • For aborting attacks, parenteral triptans, dihydroergotamine, or 100% oxygen

  • For long-term prophylaxis, verapamil, lithium, topiramate, divalproex, or a combination or galcanezumab (a monoclonal antibody) for episodic cluster

Acute attacks of cluster headache can be aborted with either a parenteral triptan or dihydroergotamine (see table Drugs for Migraine and Cluster Headaches) and/or 100% oxygen given by nonrebreathing face mask. Also, evidence suggests that acute attacks of episodic cluster headache can be treated with a handheld device that delivers noninvasive vagus nerve stimulation (1, 2).

All patients require preventive drugs because cluster headache is frequent, severe, and incapacitating. Prednisone (eg, 60 mg orally once a day) or a greater occipital nerve block (with a local anesthetic and a corticosteroid) can provide prompt temporary prevention while preventive drugs with slower onset of action (eg, verapamil, lithium, topiramate, divalproex) are initiated.

Noninvasive transcutaneous supraorbital nerve stimulation delivered using a device applied to the forehead can reduce the frequency of cluster headaches, as can noninvasive vagus nerve stimulation (3).


Drugs for Cluster Headaches*






Regular-release: 250–500 mg orally 2 times a day

Extended-release: 500–1000 mg orally once a day

Can cause alopecia, gastrointestinal upset, hepatic dysfunction, thrombocytopenia, tremor, and weight gain

Contradicted in pregnant women as prevention of migraines (risk of fetal malformation clearly outweighs any possible benefit)


300 mg orally 2 to 4 times a day

May cause weakness, thirst, tremor, and polyuria

Periodic checking of drug levels required


50–200 mg orally usually once a day

Can cause weight loss and central nervous system adverse effects (eg, confusion, depression)


240 mg once to 3 times a day

Can cause hypotension and constipation


300 mg subcutaneously once a month

Usually used when other treatments for episodic cluster headaches are ineffective



0.5–1 mg subcutaneously or IV

4 mg/mL nasal spray

Can cause nausea

Contraindicated in patients with hypertension or coronary artery disease

Cannot be used concurrently with triptans

Pulmonary-inhaled formulation under development


Almotriptan 12.5 mg orally

Eletriptan 20–40 mg orally

Frovatriptan 2.5 mg orally

Naratriptan 2.5 mg orally

Rizatriptan 10 mg orally

Sumatriptan 50–100 mg orally, 5–20 mg nasal spray, 6 mg subcutaneously, or one 6.5-mg transdermal patch, followed, if needed, by a 2nd patch after 2 hours (not to exceed 2 patches in 24 hours)

Zolmitriptan 2.5–5 mg orally or 5 mg nasal spray

Can cause flushing, paresthesias, and sense of pressure in chest or throat

Can repeat doses up to 3 times a day if headache recurs

Contraindicated in patients with coronary artery disease, uncontrolled hypertension, hemiplegic migraine, or intracranial vascular disease

Injections or nasal spray used for cluster headache

* The regular-release formulation is usually used.

† Triptans are given once, then repeated as needed.

Treatment reference

  • 1. Silberstein SD, Mechtler LL, Kudrow DB, et al: Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: Findings from the randomized, double-blind, sham-controlled ACT1 study. Headache 56 (8):1317–1332, 2016. doi: 10.1111/head.12896.

  • 2. Miller S, Sinclair AJ, Davies B, Matharu M: Neurostimulation in the treatment of primary headaches. Pract Neurol 16 (5):362–375, 2016. doi: 10.1136/practneurol-2015-001298. Epub 2016 May 5.

  • 3. Gaul C, Diener H, Solbach K, et al: EHMTI-0364. Non-invasive vagus nerve stimulation using Gammacore® for prevention and acute treatment of chronic cluster headache: Report from the randomized phase of the PREVA study. J Headache and Pain 15 (suppl 1):I7, 2014.

Key Points

  • Typically, cluster headache causes excruciating unilateral periorbital or temporal pain, with ipsilateral ptosis, lacrimation, rhinorrhea, and/or nasal congestion, in men aged 20 to 40 years.

  • Usually, patients experience ≥ 1 attack/day for 1 to 3 months, followed by remission for months to years.

  • Diagnose cluster headache based on clinical findings.

  • To abort attacks, give a parenteral triptan or dihydroergotamine (see table Drugs for Migraine and Cluster Headaches) and/or 100% oxygen by a nonrebreathing face mask.

  • To prevent attacks, use prednisone or a greater occipital nerve block for short-term relief and verapamil, lithium, topiramate, and/or galcanezumab for long-term relief.

Drugs Mentioned In This Article

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Numbness is defined as loss of sensation, either partial or complete. Numbness can occur from dysfunction anywhere along the pathway from the sensory receptors up to the cerebral cortex. A patient with dysfunction in which of the following CNS areas is most likely to present with facial and body numbness on the same side, plus an inability to perceive multiple stimuli of the same type simultaneously?
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