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Cluster Headache Medication

  • Author: Michelle Blanda, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
 
Updated: Dec 07, 2015
 

Medication Summary

Pharmacologic management of cluster headache (CH) may be divided into abortive/symptomatic and preventive/prophylactic strategies. Abortive agents are used to stop or reduce the severity of an acute attack, whereas prophylactic agents are used to reduce the frequency and intensity of individual headache exacerbations.

Inhalation of high-flow concentrated oxygen is extremely effective for aborting CH attacks, though the precise mechanism of action is poorly understood. Oxygen is an effective alternative to ergotamine. Despite the immediate availability of oxygen in the emergency department, its widespread use in outpatient setting is impractical.

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Neurologics, Other

Class Summary

Triptans may reduce the inflammation associated with migraine headaches.

Zolmitriptan (Zomig, Zomig-ZMT, Zomig Nasal Spray)

 

As a selective agonist of 5-hydroxytryptamine-1 (5-HT1) receptors in cranial arteries, zolmitriptan causes vasoconstriction and reduces the inflammation associated with antidromic neuronal transmission in CH. It can reduce the severity of headache within 15 minutes of subcutaneous injection. The intranasal form is now available in the United States, offering an attractive alternative to self-injection.

Naratriptan (Amerge)

 

As a selective agonist of 5-HT1 receptors in cranial arteries, naratriptan causes vasoconstriction and reduces the inflammation associated with antidromic neuronal transmission in CH. It can reduce the severity of headache within 15 minutes of subcutaneous injection.

Sumatriptan succinate (Imitrex, Alsuma, Sumavel DosePro)

 

As a selective agonist of 5-HT1 receptors in cranial arteries, sumatriptan causes vasoconstriction and reduces the inflammation associated with antidromic neuronal transmission in CH. It can reduce the severity of headache within 15 minutes of subcutaneous injection. The intranasal form is now available in the United States, offering an attractive alternative to self-injection.

Rizatriptan (Maxalt, Maxalt-MLT)

 

Rizatriptan is a selective agonist for 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.

Almotriptan (Axert)

 

Almotriptan is a selective 5-HT1B/1D receptor agonist used to treat acute migraine. It results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways.

Frovatriptan (Frova)

 

Frovatriptan is used to treat acute migraine. It is a selective 5-HT1B/1D receptor agonist with a long half-life (24 hours) and a low headache recurrence rate within 24 hours after taking the drug. It results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. It has unique characteristics and benefits in the acute treatment of migraine.

Eletriptan (Relpax)

 

Eletriptan is a selective serotonin agonist that specifically acts at 5-HT1B/1D/1F receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute headaches.

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Ergot Derivatives

Class Summary

Ergot alkaloids are highly effective in relieving acute CH pain. They are direct vasoconstrictors of smooth muscle in cranial blood vessels, and their activity depends on central nervous system (CNS) vascular tone at the time of administration.

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

 

Dihydroergotamine has alpha-adrenergic antagonist and serotonin antagonist effects. It is available in IV or intranasal preparations and tends to cause less arterial vasoconstriction than ergotamine tartrate.

Ergotamine (Ergomar)

 

Ergotamine has alpha-adrenergic antagonist and serotonin antagonist effects and causes constriction of peripheral and cranial blood vessels. Oral administration of ergotamine is not as effective as inhaled, rectal, or sublingual administration for treatment of acute cluster attacks. To prevent rebound headaches, avoid exceeding maximum dosage guidelines.

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Anesthetics, Topical

Class Summary

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

Lidocaine 4%, (Xylocaine)

 

Lidocaine blocks conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization and blockade of conduction. Intranasal administration of lidocaine drops is an experimental abortive therapy for CH.

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Analgesics, Topical

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.

Capsaicin (Capzasin-P)

 

Intranasal capsaicin has been successfully tested in clinical trials. This substance, derived from chili peppers, induces release of substance P, the principal chemomediator of pain impulses from the periphery to the CNS. After repeated applications, capsaicin depletes the neuron of substance P and prevents reaccumulation.

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Calcium Channel Blockers

Class Summary

These agents inhibit the initial vasoconstrictive phase of CH.

Verapamil (Calan, Verelan, Verelan PM, Covera-SR)

 

Perhaps the most effective calcium channel blocker for CH prophylaxis, verapamil inhibits calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle, thereby producing vasodilation. It can be combined with ergotamine or lithium.

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Psychiatry Agents, Other

Class Summary

Lithium’s mechanism of action in CH is unclear, though preliminary evidence suggests that it may interfere with substance P and vasoactive intestinal peptide (VIP)-induced arterial relaxation.

Lithium carbonate (Lithobid)

 

Variable responses notwithstanding, lithium is still a recommended first-line agent in CH. The narrow therapeutic window necessitates close monitoring of levels and adverse effects. A plasma lithium level of 0.6-1.2 mEq/L measured at steady state 12 hours after the last dose (ie, just before the next dose) is usually sought, but optimal plasma levels for prevention of CH are not established. It is thought to be effective against CH at serum concentrations lower than those required in bipolar disorder (0.3-0.8 mEq/L).

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Anticonvulsants

Class Summary

The mechanism of action by which anticonvulsants prevent CH is unclear; it may involve regulation of central sensitization.

Divalproex sodium (Depakote, Depakote ER)

 

Few adequate studies of divalproex are available, and results have been mixed.

Topiramate (Topamax)

 

Topiramate has been effective for prophylaxis of CH in several small prospective studies. Its exact mechanism of action in this setting is unknown.

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Corticosteroids

Class Summary

Corticosteroids are effective for CH that does not respond to lithium. They are intended for intermittent use during acute flareups. High doses of corticosteroids can ease pain within 8-12 hours, achieving maximum effectiveness in 2-3 days.

Prednisone

 

Prednisone is very effective for aborting the CH cycle or providing intermediate prophylaxis (bridging therapy between acute and prophylactic agents). It is effective for treatment of CH that does not respond to lithium. Its effects in CH may occur via inhibition of prostaglandin synthesis. Long-term use is not recommended.

Prednisolone (Millipred, Orapred, Orapred ODT, Prelone)

 

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage.

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Antiemetics and Sedatives

Class Summary

Antiemetics and sedatives are used to treat CH and emesis associated with acute attacks.

Prochlorperazine (Compro)

 

Prochlorperazine is an antidopaminergic drug that blocks postsynaptic mesolimbic dopamine receptors, has an anticholinergic effect, and can depress the reticular activating system, thereby possibly relieving nausea and vomiting.

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Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Class Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) may alleviate headache pain by inhibiting prostaglandin synthesis, reducing serotonin release, and blocking platelet aggregation. Although their effective in the treatment of headache pain tends to be patient-specific, ibuprofen is usually the drug of choice for initial therapy. Other options include naproxen, ketoprofen, flurbiprofen, indomethacin, and ketorolac.

Ibuprofen (Motrin, Advil, Addaprin, Caldolor)

 

Ibuprofen is the drug of choice for mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. Many doses are available, either with or without a prescription.

Ketoprofen

 

Ketoprofen is used for the relief of mild to moderate pain and inflammation. Small doses are indicated initially in patients with small body size, elderly patients, and persons with renal or liver disease. Doses of over 75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

Naproxen (Anaprox, Naprelan, Aleve, Naprosyn)

 

Naproxen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

Flurbiprofen

 

Flurbiprofen may inhibit cyclooxygenase, thereby inhibiting prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities.

Indomethacin (Indocin)

 

Indomethacin is absorbed rapidly; it is metabolized in the liver via demethylation, deacetylation, and glucuronide conjugation. It is useful in the diagnosis of CH because it helps other headache syndromes (eg, chronic paroxysmal hemicrania).

Ketorolac

 

Ketorolac inhibits prostaglandin synthesis by decreasing the activity of cyclooxygenase, thereby resulting in decreased formation of prostaglandin precursors.

Ketorolac nasal solution (Sprix)

 

Ketorolac inhibits cyclooxygenase, an early component of the arachidonic acid cascade, resulting in reduced synthesis of prostaglandins, thromboxanes, and prostacyclin. It has anti-inflammatory, analgesic, and antipyretic effects and is indicated for short-term (≤ 5 days) management of moderate to moderately severe pain. The bioavailability of a 31.5-mg intranasal dose (2 sprays) is approximately 60% of that of a 30-mg IM dose. The intranasal preparation delivers 15.75 mg per 100-µL spray; each 1.7-g bottle contains 8 sprays.

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Contributor Information and Disclosures
Author

Michelle Blanda, MD Chair Emeritus, Department of Emergency Medicine, Summa Health System Akron City/St Thomas Hospital; Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine

Michelle Blanda, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine

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 Heart Association, American Headache Society

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

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.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Ragasri Kumar, DO Resident Physician, Department of Neurology, Loyola University Medical Center

Disclosure: Nothing to disclose.

Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems in Cleveland

Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Lori K Sargeant, MD Consulting Staff, Summa Emergency Associates, Inc

Lori K Sargeant, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, and Ohio State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Cluster headache: Functional imaging shows activation of specific brain areas during pain. Courtesy of Wikipedia Commons.
Cluster headache (CH): Voxel-based morphometry (VBM) structural imaging shows specific brain area of CH patients' (hypothalamus) being different to non-CH patients' brains. Courtesy of Wikipedia Commons.
Non-rebreather oxygen mask with reservoir for the acute treatment of cluster headache. Courtesy of Wikipedia Commons.
 
 
 
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