Cluster Headache Medication

The pharmacologic management of CH may be divided into abortive/symptomatic and preventive/prophylactic strategies. Abortive therapy is directed at stopping or reducing the severity of an acute attack, while prophylactic agents are used to reduce the frequency and intensity of individual headache exacerbations. Due to the fleeting, short-lived nature of the attacks, effective prophylactic therapy should be considered the cornerstone of treatment. The prophylactic therapy should start at the onset of a CH cycle and continue until the patient is headache free for at least 2 weeks. The agent then may be tapered slowly to prevent recurrences.

Class Summary

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.

Class Summary

These agents may reduce the inflammation associated with migraine headaches.

Zolmitriptan (Zomig, Zomig-ZMT, 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.

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.

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.

Rizatriptan (Maxalt, Maxalt-MLT)

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

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.

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.

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.

Class Summary

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.

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.

Class Summary

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.

Class Summary

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.

Class Summary

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.

Class Summary

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).

Class Summary

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.

Topiramate (Topamax)

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

Class Summary

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.

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.