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Headache, Cluster: Treatment & Medication
Updated: Nov 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Emergency Department Care
Treatment of cluster headache is as follows.
- Oxygen (acute attack)1,2
- Oxygen (8 L/min for 10 min or 100% by mask) may abort the headache if used early.
- Mechanism of action is unknown.
- Sumatriptan1,3,2
- Sumatriptan is the most studied of the triptans in cluster headache. Subcutaneous injections can be effective, in large part, due to the rapidity of onset. Studies have indicated that intranasal administration is more effective than placebo but not as effective as injections. No evidence suggests that they are effective orally. Typical dose is 6 mg SQ with the ability to repeat in 24 hours. Nasal spray (20 mg) may also be used.
- Early studies are encouraging.
- Dihydroergotamine
- Can be abortive agent
- IV/IM; self-injections
- Intranasal 0.5 mg bilaterally2
- Analgesics/narcotics: Oral route levels are inadequate until attack is complete but often are helpful for residual soreness. Abuse potential does exist.
- Civamide and capsaicin: When applied to the nasal mucosa of patients with cluster headaches, a clinically significant decrease occurred in the number and severity of cluster headaches. Nasal burning was the most common adverse effect.
- Lidocaine: 1 mL of a 10% solution placed on a swab in each nostril for 5 minutes is possibly helpful.
Diagnosis and treatment guidelines are available from the American College of Emergency Physicians and National Headache Foundation.4,3
Consultations
Neurologic consultation may be useful if the diagnosis is in doubt or for management of difficult cases.
Medication
The goal of pharmacotherapy is to prevent the attack or alter it once it is underway. An accurate diagnosis is required when therapy is being considered.
5-HT1 receptor agonists such as sumatriptan or dihydroergotamine (DHE) with metoclopramide are often the first line of treatment. Parenteral opiates may be used if relief is inadequate. Antihistamines, such as chlorpromazine, do not appear to be helpful in relieving cluster headache symptoms. Tricyclic antidepressants are more helpful as prophylaxis of other headache syndromes. Beta-blockers may worsen bradycardia occurring during the cluster attack.
Corticosteroids
These agents are effective for cluster headaches that do not respond to lithium. They are intended for intermittent use during acute flare-ups. High doses of corticosteroids can ease pain within 8-12 h, with maximum effectiveness in 2-3 d.
Prednisone (Sterapred)
May suppress factors producing headaches. Should be used for short-lasting cluster attacks and not for prolonged therapy. More than 50% of patients show improvement.
Adult
40 mg PO qd for 2 wk; then taper over 7 d
Try alternate-day maintenance dose of 5-10 mg if attacks recur during taper
Pediatric
4-5 mg/m2/d PO; as alternative, 1-2 mg/kg
PO qd; taper over 2 wk as symptoms resolve
Tricyclic antidepressants, MAOIs, antihistamines, guanethidine, methyldopa, ergot alkaloids increase effects; atropine may block reflex tachycardia caused by norepinephrine and enhances pressor response
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation may cause adrenal crisis; may cause hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections
Antiemetics and sedatives
These agents are used to treat cluster headaches and emesis associated with acute attacks.
Prochlorperazine (Compazine)
Antidopaminergic drug that blocks postsynaptic mesolimbic dopamine receptors, has anticholinergic effect, and can depress reticular activating system, possibly responsible for relieving nausea and vomiting.
Adult
5-10 mg PO/IM tid/qid; not to exceed 40 mg/d
2.5-10 mg IV q3-4h prn; most common route given in ED; not to exceed 10 mg/dose or 40 mg/d
25 mg PR bid
Pediatric
2.5 mg PO/PR q8h or 5 mg q12h prn; not to exceed 15 mg/d
0.1-0.15 mg/kg/dose IM, change to PO as soon as possible
IV not recommended for children
Other CNS depressants or anticonvulsants may cause additive effects; with epinephrine, may cause hypotension
Documented hypersensitivity; avoid in bone marrow suppression, narrow-angle glaucoma, and severe liver or cardiac disease
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
Drug-induced Parkinson syndrome or pseudoparkinsonism occurs frequently; akathisia is most common extrapyramidal reaction in elderly patients; lowers seizure threshold; caution with history of seizures
Antidepressants
Lithium has been suggested as a therapy option because of the cyclical nature of cluster headaches, which is similar to the cyclical episodes in bipolar disorders.
Lithium (Eskalith)
Used to treat episodic and chronic cluster headache attacks. Mechanism of action unknown, although stabilization of biologic membranes may occur. Patients with chronic syndrome more responsive. Tendency for effect to wane after dramatic relief in first week.
Adult
600-900 mg PO qd
Target serum level 0.4-0.8 mEq/L (less than standard psychiatric doses)
Pediatric
<6 years: Not recommended
6-12 years: 15-60 mg/kg/d PO divided tid/qid; not to exceed usual adult dose
>12 years: Administer as in adults
Increases toxicity of thiazide diuretics, haloperidol, phenothiazines, neuromuscular blockers, carbamazepine, fluoxetine, and ACE inhibitors
Documented hypersensitivity; severe cardiovascular disease
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Toxicity closely related to serum levels and can occur at therapeutic doses; serum levels required to monitor therapy
Calcium channel blockers
These agents may be most effective at prophylaxis.2
Verapamil (Calan, Covera)
Can be combined with ergotamine or lithium. Others, including nimodipine and diltiazem, also reported to be effective.
Adult
120-360 mg (immediate release) PO tid/qid
ER form may be given qd
Pediatric
Not established
May increase carbamazepine, digoxin, and cyclosporine levels; amiodarone can cause bradycardia and decrease in cardiac output; beta-blockers may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels
Documented hypersensitivity; severe CHF; sick sinus syndrome or second- or third-degree AV block; hypotension (SBP <90 mm Hg)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause hepatocellular injury; transient elevations of transaminase levels with and without concomitant elevations in alkaline phosphatase and bilirubin levels have occurred (elevations have been transient and may disappear with continued verapamil treatment); monitor liver function periodically
Nonsteroidal anti-inflammatory agents
These agents may alleviate headache pain by inhibiting prostaglandin synthesis, reducing serotonin release, and blocking platelet aggregation. Although the effects of NSAIDs in the treatment of headache pain tend to be patient specific, ibuprofen is usually the DOC for the initial therapy. Other options include naproxen, ketoprofen, and ketorolac.
Indomethacin (Indocin)
Absorbed rapidly; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation.
Useful in diagnosis because it helps other headache syndromes (eg, chronic paroxysmal hemicrania).
Adult
Immediate release: 25-50 mg PO bid/tid
Sustained release: 75 mg PO bid; not to exceed 200 mg/d
Pediatric
1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d
Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (monitor PT closely and instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels
Documented hypersensitivity; GI bleeding; renal insufficiency
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
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia)
Ketorolac (Toradol)
Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Adult
30 mg IV single dose (most common route used in ED)
>65 years, renal impairment, or <50-kg body weight: 15 mg IV single dose
30-60 mg IM initially, followed by 15-30 mg q6h prn; not to exceed 5 d of treatment
Pediatric
Not established; recommended dose 0.4-1 mg/kg once
Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (monitor PT closely and instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; not for administration into CNS
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
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts (rare) usually return to normal during ongoing therapy; discontinue therapy if persistent leukopenia, granulocytopenia, or thrombocytopenia
Ergotamines
These are direct vasoconstrictors of smooth muscle in cranial blood vessels. Their activity depends on CNS vascular tone at the time of administration.
Dihydroergotamine (D.H.E. 45 injection, Migranal)
More effective when given early in cluster attack. Has alpha-adrenergic antagonist and serotonin antagonist effects.
Adult
1 mg IM at first sign of headache; repeat q1h; not to exceed 3 mg total dose
2 mg IV maximum dose for faster effect (most common dose 0.75-1 mg IV with an antiemetic); not to exceed 6 mg/wk
Intranasal: 1 spray into each nostril, repeat prn within 15 min; not to exceed 6 sprays/d or 8 sprays/wk
Pediatric
Not established
Increases effects of heparin; increases toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin
Documented hypersensitivity; sumatriptan or zolmitriptan within previous 24 h; MAOIs within last 2 wk
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in angina, hypertension, impaired renal or hepatic function, or peripheral vascular disease
Ergotamine tartrate (Cafergot, Cafatine, Cafetrate)
Has alpha-adrenergic antagonist and serotonin antagonist effects. Causes constriction of peripheral and cranial blood vessels. Oral administration of ergotamine not as effective as inhaled or sublingual routes in treatment of acute cluster attacks.
Adult
2 tab PO at onset of attack and 1 tab PO q30min prn; not to exceed 6 tab per attack or 10 tab/wk
1 tab SL at first sign of attack and 1 tab SL q30min; not to exceed 3 tab/d or 5 tab/wk
1 supp PR at first sign of attack with a second dose after 1 h if necessary; not to exceed 2 supp/attack or 5 supp/wk
Pediatric
Not established
Increases effects of heparin; increases toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin
Documented hypersensitivity; avoid in hepatic or renal disease, peptic ulcer disease, sepsis, or peripheral vascular disease
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Do not give more than 3 tab/d or 6 inhalations/d; do not give more than 10 mg/wk or 15 inhalations/wk
Avoid extra doses for abortive therapy in individual attacks; avoid using prolonged regimens because of danger of causing gangrene or dependency
5-HT1 receptor agonist
Stimulation of 5-HT1 receptors produces a direct vasoconstrictive effect and may abort the attack.
Eletriptan (Relpax)
Selective serotonin agonist. Specifically acts at 5-hydroxytryptamine 1B/1D/1F (5-HT1B/1D/1F) receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute migraine.
Adult
20-40 mg/dose PO at onset of migraine; if initial dose ineffective, may repeat dose once after 2 h; not to exceed 80 mg/d
Pediatric
<18 years: Not established
Potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) may increase toxicity; concurrent administration with ergot-containing drugs may increase vasospastic reactions
Documented hypersensitivity; severe hepatic impairment; age >65 y; administration within 72 h of potent CYP3A4 inhibitors
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)
Almotriptan (Axert)
Used to treat acute migraine. Selective 5-HT1B/1D receptor agonist. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways.
Adult
6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d
Pediatric
Not established
Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity
Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension
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)
Selective 5-HT1B/1D receptor agonist. 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. Studies demonstrate prolonged presence of frovatriptan in bloodstream, and few migraine patients experienced recurrence of headache within 24 h of taking frovatriptan.
Adult
2.5 mg PO once at onset of migraine attack
Pediatric
Not established
Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination
Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension
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
Sumatriptan succinate (Imitrex)
Selective agonist for serotonin 5-HT1 receptors in cranial arteries. Suppresses inflammation associated with migraine headaches.
Adult
25 mg PO; if satisfactory response not seen in 2 h, additional dose of up to 100 mg; additional dose at intervals of 2 h prn; not to exceed 300 mg/d
6 mg SC, if satisfactory response not seen in 1 h, additional 6 mg SC may be administered; not to exceed 2 injections/24 h
Intranasal: Single dose of 5, 10, or 20 mg in one nostril; give 10 mg dose by administering single 5 mg dose in each nostril; if satisfactory response not seen in 2 h, additional dose may be administered; not to exceed 40 mg/d
Pediatric
Not established
Ergot-containing drugs, SSRIs, and MAOIs increase toxicity
Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension
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
Zolmitriptan (Zomig, Zomig-ZMT)
As selective agonists of serotonin 5-HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in cluster headache. Can reduce severity of headache within 15 min of SC injection.
Adult
2.5 mg PO initially; repeat dose after 2 h if headache returns; not to exceed 10 mg/d
Pediatric
Not established
Toxicity increases when administered concomitantly with ergot-containing drugs, SSRIs, and MAOIs
Documented hypersensitivity; ischemic heart disease and uncontrolled hypertension; do not administer within 24 h of taking another serotonin agonist or ergotamine or within 2 wk of taking a MAOI
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
Naratriptan (Amerge, Naramig)
As selective agonists of serotonin 5-HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in cluster headache. Can reduce severity of headache within 15 min of SC injection.
Adult
1-2.5 mg PO q4h prn for headache; not to exceed 5 mg/d
Pediatric
<12 years: Not established
>12 years: 2.5 mg PO initially; not to exceed 5 mg/d
Oral contraceptives may significantly increase concentrations and cause prolonged vasospastic reactions to occur, avoid concurrent use within 24 h of each other; toxicity may increase when administered concomitantly with ergot-containing drugs, SSRIs, and MAOIs
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)
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 angina before receiving additional doses; monitor ECG if dosing resumed and similar symptoms recur
Rizatriptan (Maxalt, Maxalt-MLT)
Selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.
Adult
5-10 mg PO q2h prn for headache; not to exceed 30 mg/d
Pediatric
Not established
Toxicity increases when administered concomitantly with ergot-containing drugs, SSRIs, and MAOIs
Documented hypersensitivity
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
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| Differential Diagnoses & Workup: Headache, Cluster |
 Treatment & Medication: Headache, Cluster |
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References
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Further Reading
Keywords
cluster headache, cluster headache symptoms, cluster headache causes, histamine headache, cluster headache treatment, histaminic headache, Horton's cephalalgia, Horton's headache, neurovascular headache, episodic cluster headaches, chronic cluster headache, migraine
