eMedicine Specialties > Neurology > Headache and Pain

Cluster Headache

Ragasri Kumar, DO, Resident Physician, Department of Neurology, Loyola University Medical Center
Rima M Dafer, MD, MPH, FAHA, Associate Professor, Department of Neurology and Neurological Surgery, Loyola University, Chicago Stritch School of Medicine

Updated: Sep 4, 2009

Introduction

Background

Cluster headache (CH) is a primary neurovascular primary headache disorder characterized by severe strictly unilateral, typically retro-orbital or periorbital, short-lasting headaches accompanied by prominent cranial facial parasympathetic autonomic features.¹

Pathophysiology

The underlying pathophysiology of CH is not completely understood.^2,3 The periodicity of the attacks in CH suggests the involvement of a biological clock within the hypothalamus, with central disinhibition of the nociceptive and autonomic pathways specifically the trigeminal nociceptive pathways. The posterior hypothalamic grey matter has been identified as the key area for the basic defect in CH by neuroimaging with positron emission tomography (PET) and anatomical imaging with voxel-based morphometry.¹ Furthermore, altered habituation patterns and changes were observed within the trigeminal-facial neuronal circuitry secondary to central sensitization, in addition to dysfunction of the serotonergic raphe nuclei-hypothalamic pathways. More recently, functional hypothalamic dysfunction has recently been confirmed by abnormal metabolism based on the N-acetylaspartate neuronal marker in magnetic resonance spectroscopy.⁴

Frequency

United States

The exact prevalence is unknown. Kudrow estimated 0.4% in men and 0.08% in women.⁵

International

In an extensive study of 100,000 inhabitants of the republic of San Marino, the prevalence was 0.07%.

Race

CH has been suggested to be slightly more prevalent in the African American population.

Sex

CH is more common in men, with a male-to-female ratio of 3:1.

Age

Although it is more common in the third decade of life, CH has been reported in patients as young as 1 year and as old as 79 years.

Clinical

History

• Attacks of cluster headache (CH) are typically short in duration (5-180 min) and occur with a frequency from once every other day to 8 times a day, particularly during sleep or early morning hours, usually corresponding with onset of REM sleep.³ As opposed to migraine, CH is not preceded by aura and is not usually associated with accompanying symptoms such as nausea, vomiting, photophobia, or osmophobia. Typically, a cluster lasts 2 weeks to 3 months.
• Pain is described as excruciating, stabbing, sharp, and lancinating, rather than throbbing. The pain is unilateral, in the periorbital, retroorbital, or temporal regions. Sometimes, the pain radiates to the cheek, jaw, occipital, and nuchal regions. CH may rarely switch sides.
• Pain is accompanied by cranial parasympathetic symptoms including ipsilateral lacrimation, conjunctival injection, rhinorrhea, eyelid edema, ptosis, and miosis.³
• Alcoholic products and tobacco may precipitate an attack.
• Some triggers include hot weather, watching television, nitroglycerin, stress, relaxation, extreme temperatures, glare, allergic rhinitis, and sexual activity.
• During an attack of CH, patients may become agitated and extremely restless. Patients do not like to lie down to rest; instead, they are restless and prefer to pace or move around. In desperation, patients may rock, sit, pace, bang themselves against a hard surface, scream in pain, or crawl on the floor.
• Classification of CH: The International Headache Society (IHS) classifies CH by duration as episodic or chronic.⁶
  • Episodic CH occurs in periods lasting from 7 days to 1 year; cluster attacks are separated by pain-free intervals lasting at least 2 weeks.
  • Chronic CH is defined as that occurring for more than 1 year without remission or with remissions lasting less than 2 weeks. It is subdivided into chronic CH from onset and chronic CH evolving from episodic.
• Structural lesions have been described with CH and should be suspected if the presentation is atypical. Atypical features may include the following:
  • Absence of a periodic pattern
  • Residual headache between exacerbations
  • Bilaterality
  • Incomplete or minimal response to standard therapy
  • Presence of lateralizing findings on examination (other than Horner syndrome) 
• Patients with CH have increased risk of suicide attempts, alcohol use, cigarette smoking, and peptic ulcer disease.

Physical

• The association of prominent autonomic phenomena is a hallmark of cluster headache (CH). Such signs include ipsilateral nasal congestion and rhinorrhea, lacrimation, conjunctival hyperemia, facial diaphoresis, palpebral edema, and complete or partial Horner syndrome (which may persist between attacks). Tachycardia is a frequent finding.
• A distinctive CH face is described as follows: leonine facial appearance, multifurrowed and thickened skin with prominent folds, a broad chin, vertical forehead creases, and nasal telangiectasias.

Causes

• The exact cause of cluster headache (CH) is unknown.
• The disorder is sporadic, although rare cases of an autosomal dominant pattern within a single family have been reported.

Differential Diagnoses

Other Problems to Be Considered

Arteriovenous malformations
Brainstem syndromes
Metastatic lung carcinoma
Nasopharyngeal carcinoma
Malignant and nonmalignant pain syndromes
Raeder paratrigeminal syndrome
Vertebral artery aneurysm
Cerebral venous thrombosis⁷
Pituitary tumors

Workup

Imaging Studies

Neuroimaging with assessment of intracranial and cervical vasculature, and the sellar and paranasal region, is recommended in every patient with atypical presentations of trigeminal autonomic headaches.

Treatment

Medical Care

Pharmacologic management of cluster headache (CH) may be classified as abortive/symptomatic or preventive/prophylactic. See Medication section for a detailed discussion.

Other agents that have been used to treat CH are olanzapine⁸ and kudzu.⁹ Their effectiveness has not been determined.

Surgical Care

• Invasive nerve blocks and ablative neurosurgical procedures (eg, percutaneous radiofrequency, trigeminal gangliorhizolysis, rhizotomy) all have been implemented successfully in cases of refractory CH. Percutaneous radiofrequency ablation may achieve success in 50% of patients, with fair-to-good results in 20% and failure in about 30%. Side effects include facial dysesthesia, corneal sensory loss, and anesthesia dolorosa.
• Gamma-knife radiosurgery has provided a less invasive alternative for pervasive CH.
• Botulinum toxin injections to manage cluster headaches have produced limited success.¹⁰
• Greater occipital nerve block may be beneficial in aborting CH.⁸
• Deep brain stimulation with implantation of stimulating electrodes under stereotactic guidance into the ipsilateral posterior inferior hypothalamus has emerged as a potential option for chronic CH refractory to pharmacological treatment.^11,12,13,14 This technique is invasive and is associated with significant risk of complications, including intracranial hemorrhage.¹⁵
• Recently, sphenopalatine ganglion stimulation has shown effectiveness in selected patients with chronic CH.¹⁶

Medication

Abortive Agents: Oxygen

These agents are administered to abort an attack of CH. Because of the duration of the attacks, they must provide immediate relief.

High-flow oxygen

Inhalation of high-flow, concentrated oxygen extremely effective for aborting CH attack. Precise mechanism of action poorly understood. Effective alternative to ergotamine. Despite immediate availability of oxygen in ED, its widespread use in outpatient setting limited by impracticality.

Dosing

Adult

6-8 L/min concentrated (100%) oxygen by face mask for no longer than 15 min

Pediatric

Not established

Interactions

None reported

Contraindications

None reported

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Inspired oxygen concentrations between 50-100% have a substantial risk of lung damage

Abortive Agents: Triptans

These agents may reduce the inflammation associated with migraine headaches.

Zolmitriptan (Zomig, Zomig-ZMT); Intranasal zolmitriptan (Zomig Nasal Spray)

As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in CH. Can reduce severity of headache within 15 min of SC injection. Intranasal form recently introduced in US, offering attractive alternative to self-injections.

Dosing

Adult

2.5-5 mg PO; repeat after 2 h prn; not to exceed 10 mg/d; 5 mg intranasally prn may repeat in 2 h prn
Nasal spray: Administer 5 mg (as a single puff) intranasally; if headache recurs, may repeat dose after 2 h, not to exceed 10 mg/24 h

Pediatric

Not established

Interactions

Not to be used on the same day as another ergot derivative or triptan; toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs

Contraindications

Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; use of MAOIs in last 2 wk

Precautions

Pregnancy

Precautions

May cause facial flushing, numbness, paresthesias, and chest pain of noncardiac origin; significant elevation in blood pressure, including hypertensive crisis, has been reported in patients without history of hypertension; peripheral vascular ischemia, colonic ischemia with abdominal pain, and bloody diarrhea have occurred

Naratriptan (Amerge, Naramig)

As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in CH. Can reduce severity of headache within 15 min of SC injection.

Dosing

Adult

1-2.5 mg PO q4h prn for headache; not to exceed 5 mg/d

Pediatric

Not established

Interactions

Oral contraceptives may significantly increase naratriptan concentrations and prolonged vasospastic reactions may occur, avoid concurrent use within 24 h of each other; toxicity may increase when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs

Contraindications

Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; cerebrovascular or peripheral vascular syndromes; severe renal impairment (CrCl < 15 mL/min); severe hepatic impairment (Child-Pugh grade C)

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Chest, jaw or neck tightness may occur after 5-HT1 agonist administration; atypical sensations over precordium (pain, tightness, pressure, heaviness) may occur (rarely associated with arrhythmias or ischemic ECG changes); evaluate patients with signs or symptoms suggestive of angina for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; monitor ECG if dosing resumed and similar symptoms recur

Sumatriptan succinate (Imitrex)

As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in CH. Can reduce severity of headache within 15 min of SC injection. Intranasal form recently introduced in US, offering attractive alternative to self-injections.

Dosing

Adult

6 mg SC, followed by second injection prn at least 1 h after first; not to exceed 2 injections/d
25-100 mg PO, followed by second dose 2 h later prn; not to exceed 300 mg/d 1 spray (5-20 mg) in 1 nostril or 1 spray (5 mg) in each nostril; may repeat in 2 h prn; not to exceed 40 mg/d

Pediatric

Not established

Interactions

Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs

Contraindications

Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, and bloody diarrhea may occur rarely when administering medication

Rizatriptan (Maxalt, Maxalt-MLT)

Selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.

Dosing

Adult

5-10 mg PO q2h prn for headache; not to exceed 30 mg/d

Pediatric

Not established

Interactions

Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur when administering this medication

Almotriptan (Axert)

Used to treat acute migraine. Selective 5-HT_1B/1D receptor agonist. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways.

Dosing

Adult

6.25-12.5 mg PO at onset of headache; may repeat once, not to exceed 25 mg/d

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP450-3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity

Contraindications

Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Decrease dose and do not exceed 12.5 mg/d in renal or hepatic impairment

Frovatriptan (Frova)

Used to treat acute migraine. Selective 5-HT_1B/1D receptor agonist with long half-life of 24 h and low headache recurrence rate within 24-hour period of taking the drug. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. Has unique characteristics and benefits in the acute treatment of migraine.

Dosing

Adult

2.5 mg PO once at onset of migraine attack

Pediatric

Not established

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination

Contraindications

Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur

Eletriptan (Relpax)

Selective serotonin agonist. Specifically acts at 5-hydroxytryptamine 1B/1D/1F (5-HT_1B/1D/1F) receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute headaches.

Dosing

Adult

20-40 mg/dose PO at onset of headache; if initial dose ineffective, may repeat dose once after 2 h; not to exceed 80 mg/d

Pediatric

<18 years: Not established

Interactions

Potent CYP450 3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) may increase toxicity; concurrent administration with ergot-containing drugs may increase vasospastic reactions

Contraindications

Documented hypersensitivity; severe hepatic impairment; age >65 y; administration within 72 h of potent CYP450 3A4 inhibitors

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients with known or suspected coronary artery disease may have increased risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events (5-HT¹ agonists may cause coronary vasospasm)

Abortive Agents: Ergot Alkaloids

These agents are highly effective in relieving acute CH pain.

Dihydroergotamine (D.H.E. 45 injection, Migranal)

Available in IV or intranasal preparations, tends to cause less arterial vasoconstriction than ergotamine tartrate.

Dosing

Adult

Up to 2 mg IV; not to exceed 2 mg/dose or 6 mg/wk 1 mg IM/SC at first sign of onset; not to exceed 3 mg total 1 spray (0.5 mg) into each nostril; not to exceed 6 sprays/d or 8 sprays/wk

Pediatric

Not established

Interactions

May increase effects of heparin; erythromycin, clarithromycin, nitroglycerin, propranolol, and troleandomycin may increase toxicity

Contraindications

Documented hypersensitivity; within 24 h of sumatriptan, zolmitriptan, other serotonin agonists, or ergotlike agents; use of MAOIs within last 2 wk

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Use caution in patients with hypertension, angina, peripheral vascular disease, or impaired renal or hepatic function

Ergotamine (Cafatine, Cafergot, Cafetrate, Ercaf)

Vasoconstrictor of smooth muscle in cranial blood vessels, alpha-adrenergic blocker, and nonselective 5-HT agonist. PR or SL preparations of ergotamine tartrate preferred to PO because of immediate onset of action. Avoid exceeding maximum dosage guidelines to prevent rebound headaches.

Dosing

Adult

2 tabs PO at first sign of onset, followed by 1 tab q30min prn; not to exceed 6 tabs/attack or 10 tabs/wk 1 tab SL at first sign of onset, followed by 1 tab q30min prn; not to exceed 3 tabs/24h or 5 tabs/wk 1 supp PR at first sign of onset, followed by second dose prn after 1 h; not to exceed 2 supp/attack or 5 supp/wk

Pediatric

Not established

Interactions

Erythromycin, troleandomycin, and other macrolide antibiotics may increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Use caution in patients with history of hypertension or coronary or peripheral arterial insufficiency; use caution in elderly persons, as may precipitate angina or MI or aggravate intermittent claudication; avoid prolonged administration or excessive dosage, since increases danger of ergotism or gangrene; patients who take for extended periods may become dependent

Abortive Agents: Anesthetics

Local anesthetics stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents initiation and transmission of nerve impulses, thereby producing the local anesthetic action.

Intranasal lidocaine 4% (Xylocaine)

An experimental abortive therapy in CH, blocks conduction of nerve impulses by decreasing neuronal membrane's permeability of sodium ions, which results in inhibition of depolarization and blockade of conduction. Effective in 2 separate clinical trials. Intranasal administration of lidocaine drops requires specific and, for many patients, difficult technique.

Dosing

Adult

4% solution intranasally; actual dose not established

Pediatric

Not established

Interactions

May enhance effects of succinylcholine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use extreme caution in patients with marked hypoxia, severe respiratory depression, or bradycardia

Oral Opioids and Other Analgesics

The short-lived and unpredictable character of CH precludes the effective use of oral narcotics or analgesics. Despite their lack of efficacy, these substances are abused by some CH sufferers.

Narcotics are not recommended in aborting cluster headaches.

Intranasal capsaicin

This experimental therapy successfully tested in clinical trials. Derived from chili peppers, induces release of substance P, principal chemomediator of pain impulses from periphery to CNS. After repeated applications, depletes neuron of substance P and prevents reaccumulation.

Dosing

Adult

Few drops of capsaicin solution applied to ipsilateral nostril

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid contact with eyes; irritant to mucosal membranes, should be used with caution; warn patients about nasal cavity irritation, burning, congestion, drainage, and sneezing while using

Prophylactic Agents: Calcium Channel Blockers

These agents inhibit the initial vasoconstrictive phase of CH.

Verapamil (Calan, Verelan, Covera-HS)

Perhaps most effective calcium channel blocker for CH prophylaxis, inhibits calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle, thereby producing vasodilation.

Dosing

Adult

Immediate release: 120-360 mg/d PO divided tid/qid
Extended release form may be given qd

Pediatric

Not established

Interactions

Phenobarbital, hydantoins, vitamin D, sulfinpyrazone, and rifampin may decrease serum concentrations by increasing hepatic metabolism; amiodarone may increase toxicity; beta blockers may increase cardiac depressant effects on AV conduction; cimetidine may increase serum levels; may increase cyclosporine, doxorubicin, theophylline, carbamazepine, vecuronium, and digoxin serum levels

Contraindications

Documented hypersensitivity; sinus bradycardia; cardiogenic shock; advanced heart block; ventricular tachycardia; congestive heart failure; atrial fibrillation or flutter associated with accessory conduction pathways

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use caution in patients with sick-sinus syndrome, severe left ventricular dysfunction, hepatic or renal impairment, or hypertrophic cardiomyopathy; monitor ECG and blood pressure closely in patients with supraventricular tachycardia receiving IV therapy; adverse effects include constipation and water retention; patients intolerant of verapamil should try nimodipine, diltiazem, or nifedipine

Prophylactic Agents: Mood Stabilizers

Mechanism of action of lithium in CH is unclear, although preliminary evidence suggests that it may interfere with substance P and vasoactive intestinal peptide–induced arterial relaxation.

Lithium carbonate (Eskalith, Lithane, Lithobid, Lithonate, Lithotabs)

Effectively prevents CH (particularly in its more chronic forms) and treats bipolar mood disorder, another cyclic illness. Responses variable, but still recommended first-line agent in CH. Narrow therapeutic window requires close monitoring of levels and adverse effects. Plasma lithium level of 0.6-1.2 mEq/L measured at steady state, 12 h after last dose (ie, just before next dose), usually sought, but optimal plasma levels for prevention of CH not established. Thought effective in CH at serum concentrations lower than those required in bipolar disorder (0.3-0.8 mEq/L).

Dosing

Adult

600-900 mg/d PO in divided doses; increase to 600-1200 mg/d divided bid/qid prn

Pediatric

Not established

Interactions

Thiazide diuretics, NSAIDs, haloperidol, phenothiazines, neuromuscular blockers, carbamazepine, fluoxetine, and ACE inhibitors may increase serum levels and toxicity; theophylline, caffeine, and other xanthines decrease effects

Contraindications

Documented hypersensitivity; severe cardiovascular or renal disease

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Lithium toxicity can occur at therapeutic doses; use caution in patients with cardiovascular or thyroid disease, severe debilitation, dehydration, or sodium depletion, or in patients taking diuretics; adverse effects include tremor, polyuria, diarrhea, nausea, fatigue, weight gain, and thyroid dysfunction; renal toxicity with tubular damage and interstitial fibrosis may occur; CNS toxicity manifested by confusion and ataxia

Prophylactic Agents: Anticonvulsants

Efficacy in the prophylaxis of CH has been demonstrated in a few relatively small controlled studies. Unclear mechanism of action for the prevention of CH. May act by regulating central sensitization.

Divalproex sodium (Depakene, Depakote)

Few adequate studies available, with mixed results.

Dosing

Adult

Typically started at 500 mg PO qd; may titrate up to 3,000 mg/d (bid dosing for doses >1,500 mg)

Pediatric

Not established

Interactions

Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients

Contraindications

Documented hypersensitivity; liver impairment; urea cycle disorders; pregnancy (high risk of teratogenesis)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Should be used with caution in patients with renal insufficiency, in elderly patients, and in patients with bleeding diathesis

Topiramate (Topamax)

Effective in several small prospective studies. Exact mechanism of action in CH headache unknown.

Dosing

Adult

Typically started at 25 mg qhs; titrate up very slowly by 25-mg weekly increments to a bid dosing; target dose should be 100-200 mg/d

Pediatric

Not established

Interactions

May increase phenytoin levels; use with ethosuximide may augment risk for CNS depression; may reduce effectiveness of estrogen-containing contraceptives; concomitant use with carbonic anhydrase inhibitors may increase risk of nephrolithiasis

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with history of nephrolithiasis; caution in severe dehydration or diarrhea

Corticosteroids

These agents are extremely effective in terminating a CH cycle and in preventing immediate headache recurrence. High-dose prednisone is prescribed for the first few days, followed by a gradual taper. The simultaneous use of standard prophylactic agents (eg, verapamil) is recommended. The mechanism of action in CH is still subject to speculation.

Prednisone (Sterapred)

Very effective in aborting CH cycle or as intermediate prophylaxis (bridging therapy between acute and prophylactic agents). Effective for treatment of CH not responsive to lithium or methysergide. Effects in CH may occur via inhibition of prostaglandin synthesis. Long-term use not recommended.

Dosing

Adult

40-60 mg/d PO in divided doses for 5 d, followed by slow taper over 2-4 wk

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; systemic fungal infections or serious infections, except septic shock or tuberculous meningitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use cautiously in patients with diabetes, hypothyroidism, cirrhosis, congestive heart failure, thromboembolic disorders, or ulcerative colitis; chronic use may lead to gastric ulceration, immunosuppression, electrolyte disturbances, weight gain, and osteopenia

Methysergide (Sansert)

Useful in patients unresponsive to lithium. Although of ergotamine chemical class, actions differ, since has minimal ergotaminelike vasoconstrictive properties and significantly greater serotoninlike properties. Very effective in episodic and chronic CH prophylaxis. Often effective in reducing pain frequency, particularly in younger patients with episodic CH. If no improvement after 3 wk, unlikely to be beneficial. Do not give continuously for > 6 mo. Drug-free interval of 3-4 wk must follow each 6-mo course. Product no longer available in the United States.

Dosing

Adult

2-8 mg/d PO

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; peripheral vascular disease; severe arteriosclerosis; pulmonary disease; severe hypertension; phlebitis; serious infections

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Use > 6 mo discouraged, because long-term therapy may cause retroperitoneal fibrosis and fibrotic thickening of cardiac valves (drug holiday recommended to avoid these effects); adverse GI reactions most commonly affect compliance; use caution in renal or hepatic impairment; adverse effects include leg cramps, paresthesias, edema, and skin discoloration

Follow-up

Prognosis

• Eighty percent of patients with episodic cluster headache (CH) tend to maintain the episodic form.
• Episodic CH eventually transforms into chronic CH in 4-13% of patients. Intermediate (mixed) forms may occur.
• Prolonged, spontaneous remissions have been described in up to 12% of patients in some series, particularly in episodic CH. Chronic CH is more relentless and may persist in this form in up to 55% of cases. Less frequently, chronic CH may remit into an episodic form.
• Generally, CH is a lifelong problem.
• Pharmacologic intervention may play a part in the transformation of chronic CH into the episodic form; otherwise, it does not influence outcome.
• Late onset of this disorder, along with male sex and a previous history of episodic CH, predict a less favorable course.

Patient Education

• For excellent patient education resources, see eMedicine's Headache Center. Also, visit eMedicine's patient education articles Causes and Treatments of Migraine and Related Headaches, Cluster Headache, Alternative and Complementary Approaches to Migraine and Cluster Headaches, Cluster Headache FAQs, and Understanding Migraine and Cluster Headache Medications.

Miscellaneous

Special Concerns

Cluster headache in pregnancy

• Treatment options for cluster headache (CH) in pregnancy are poorly documented. The first line of treatment is pure oxygen via nonrebreather mask.
• Triptans and ergots alkaloids should be avoided during pregnancy.
• The use of selective preventive medications, which are rated pregnancy category B, should be discussed thoroughly with the patient and her obstetrician.¹⁷

References

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Keywords

cluster headache, CH, Bing-Horton syndrome, histaminic cephalalgia, cluster migraine, paroxysmal nocturnal cephalalgia, red migraine, erythromelalgia of the head, sphenopalatine neuralgia, migrainous neuralgia, periorbital pain, Horton’s headache

Contributor Information and Disclosures

Author

Ragasri Kumar, DO, Resident Physician, Department of Neurology, Loyola University Medical Center
Disclosure: Nothing to disclose.

Coauthor(s)

Rima M Dafer, MD, MPH, FAHA, Associate Professor, Department of Neurology and Neurological Surgery, Loyola University, Chicago Stritch School of Medicine
Rima M Dafer, MD, MPH, FAHA is a member of the following medical societies: American Academy of Neurology, American Headache Society, and American Heart Association
Disclosure: Nothing to disclose.

Medical Editor

Joseph Carcione Jr, DO, MBA, Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans
Joseph Carcione Jr, DO, MBA is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

James H Halsey, MD, Professor, Department of Neurology, University of Alabama Medical Center
James H Halsey, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neuroimaging, Medical Association of the State of Alabama, New York Academy of Sciences, Pan American Medical Association, Sigma Xi, Society for Neuroscience, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Medivations Honoraria Consulting

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