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Cluster Headache

By Stephen D. Silberstein, MD, Professor of Neurology and Director, Headache Center, Sidney Kimmel Medical College at Thomas Jefferson University

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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, 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 mo, 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

Symptoms of cluster headache are distinctive. Attacks often 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 min to 1 h. 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.


  • 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 sec) 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 NSAIDs.


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

  • For long-term prophylaxis, verapamil, lithium, topiramate, divalproex, or a combination

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.

All patients require preventive drugs because cluster headache is frequent, severe, and incapacitating. Prednisone (eg, 60 mg po once/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.

Drugs for Migraine and Cluster Headaches*






10–100 mg po at bedtime

Used only for migraines

Has anticholinergic effects; causes weight gain

Helpful for patients with insomnia

Small doses often effective


Atenolol 25–100 mg po once/day

Metoprolol 50–200 mg po once/day

Nadolol 20–160 mg po once/day

Propranolol 20–160 mg po bid

Timolol 5–20 mg po once/day

Used only for migraines

Only beta-blockers without intrinsic sympathomimetic activity used

Avoided in patients with bradycardia, hypotension, diabetes, or asthma


Regular-release: 250–500 mg po bid

Extended-release: 500–1000 mg po once/day

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


300 mg po bid to qid

Used only for cluster headaches

May cause weakness, thirst, tremor, and polyuria

Periodic checking of drug levels required


First-line treatment for chronic migraine


50–200 mg po usually once/day

Can cause weight loss and CNS adverse effects (eg, confusion, depression)


240 mg once/day to tid

Most useful for patients with cluster headache

Can cause hypotension and constipation



0.5–1 mg sc 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 po

Eletriptan 20–40 mg po

Frovatriptan 2.5 mg po

Naratriptan 2.5 mg po

Rizatriptan 10 mg po

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

Zolmitriptan 2.5–5 mg po or 5 mg nasal spray

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

Can repeat doses up to 3 times/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


500–1000 mg IV

Usually for patients who cannot tolerate triptans or vasoconstrictors

With long-term use, can cause alopecia, GI upset, hepatic dysfunction, thrombocytopenia, tremor, and weight gain

*Drugs can be used for either type of headache unless specified otherwise.

The regular-release formulation is usually used.

Triptans are given once, then repeated as needed.

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 yr.

  • Usually, patients experience ≥ 1 attack/day for 1 to 3 mo, 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 divalproex for long-term relief.

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