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Cluster Headache


Stephen D. Silberstein

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Reviewed/Revised Apr 2023

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 patients with migraine 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).

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:

Chronic paroxysmal hemicrania and hemicrania continua, unlike SUNCT and cluster headache (and migraine Migraine Migraine is an episodic primary headache disorder. Symptoms typically last 4 to 72 hours and may be severe. Pain is often unilateral, throbbing, worse with exertion, and accompanied by symptoms... read more ), 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, of episodic cluster, verapamil, lithium, topiramate, divalproex, or a combination or galcanezumab

All patients with cluster headache 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. Galcanezumab (a monoclonal antibody that binds the calcitonin gene-related peptide [CGRP] ligand) is usually used only when other treatments for episodic cluster headaches are ineffective.

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 Treatment references Cluster headaches cause excruciating, unilateral periorbital or temporal pain, with ipsilateral autonomic symptoms (ptosis, lacrimation, rhinorrhea, nasal congestion). Diagnosis is clinical... read more ).

Treatment references

  • 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 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

Drug Name Select Trade
DHE 45, Migranal, TRUDHESA
Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM
Eskalith, Eskalith CR, Lithobid
EPRONTIA, Qudexy XR, Topamax, Topamax Sprinkle, Topiragen , Trokendi XR
Indocin, Indocin SR, TIVORBEX
Zomig, Zomig Nasal Spray, Zomig -ZMT
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
Fortical , Miacalcin
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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