Antimigraine Drugs

Definition

Antimigraine drugs are medicines used to prevent or reduce the severity of migraine headaches.

Purpose

Migraine headaches usually cause a throbbing pain on one side of the head. Nausea, vomiting, dizziness, increased sensitivity to light and sound, and other symptoms may accompany the pain. The attacks may last for several hours or for a day or more and may come as often as several times a week. Some people who get migraine headaches have warning signals before the headaches begin, such as restlessness, tingling in an arm or leg, or seeing patterns of flashing lights. This set of signals is called an aura. The antimigraine drugs discussed in this section are meant to be taken as soon as the pain begins, to relieve the pain and other symptoms. Other types of drugs, such as antiseizure medicines, antidepressants, calcium channel blockers and beta blockers, are sometimes prescribed to prevent attacks in people with very severe or frequent migraines.

Description

Migraine is thought to be caused by electrical and chemical imbalances in certain parts of the brain. These imbalances affect the blood vessels in the brain—first tightening them up, then widening them. As the blood vessels widen, they stimulate the release of chemicals that increase sensitivity to pain and cause inflammation and swelling. Antimigraine drugs are believed to work by correcting the imbalances and by tightening the blood vessels.

Examples of drugs in this group are ergotamine (Cafergot), naratriptan (Amerge), sumatriptan (Imitrex), rizatriptan (Maxalt), almotriptan (Axert), and zolmitriptan (Zomig). Methysergide maleate (Sansert) may be used by patients whose headaches are not controlled by other drugs, while some patients do well on other drugs. For example, combinations or ergotamine and caffeine may be very effective. The caffeine acts by constricting blood vessels to relieve the headache. Sometimes, an analgesic such as acetaminophen, caffeine, and a barbiturate which acts as a sedative, are combined, as in Fioricet and similar compounds. These medicines are available only with a physician's prescription and come in several forms. Ergotamine is available as tablets and rectal suppositories; sumatriptan as tablets, injections, and nasal spray; and zolmitriptan as tablets.

Antimigraine drugs are used to treat headaches once they have started. These drugs should not be taken to prevent headaches.

Some patients are given anti-epileptic drugs, which are also known as anticonvulsants, to treat migraine headaches. As of 2003, sodium valproate (Epilim) is the only anticonvulsant approved by the Food and Drug Administration (FDA) for prevention of migraine. Such newer anticonvulsants as gabapentin (Neurontin) and topiramate (Topamax) are being evaluated as migraine preventives as of early 2004.

Recommended dosage

Recommended dosage depends on the type of drug. Typical recommended dosages for adults are given below for each type of drug.

Ergotamine

Take at the first sign of a migraine attack. Patients who get warning signals (aura) may take the drug as soon as they know a headache is coming.

TABLETS. No more than 6 tablets for any single attack.

No more than 10 tablets per week.

SUPPOSITORIES. No more than 2 suppositories for any single attack.

No more than 5 suppositories per week.

Naratriptan

Take as soon as pain or other migraine symptoms begin. Also effective if taken any time during an attack. Do not take the drug until the pain actually starts as not all auras result in a migraine.

TABLETS. Usual dose is one 1-mg tablet taken with water or other liquid.

Doses of 2.5-mg may be used, but they may cause more side effects.

If the headache returns or if there is only partial response, the dose may be repeated once after 4 hours, for a maximum dose of 5 mg in a 24-hour period. Larger doses do not seem to offer any benefit.

Sumatriptan

Take as soon as pain or other migraine symptoms begin. Also effective if taken any time during an attack. Do not take the drug until the pain actually starts as not all auras result in a migraine.

TABLETS. Usual dose is one 25-mg tablet, taken with water or other liquid.

Doses should be spaced at least 2 hours apart.

Anyone with liver disease should consult with a physician for proper dosing.

INJECTIONS. No more than 6 mg per dose, injected under the skin.

No more than two 6-mg injections per day. These doses should be taken at least 1 hour apart.

Zolmitriptan

Take as soon as symptoms begin.

TABLETS. Usual dose is 1-5 mg. Additional doses may be taken at 2-hour intervals.

KEY TERMS

Anticonvulsant— A type of drug given to prevent seizures. Some patients with migraines can be treated effectively with an anticonvulsant.

Aura— A set of warning symptoms, such as seeing flashing lights, that some people have 10-30 minutes before a migraine attack.

Inflammation— Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Status migrainosus— The medical term for an acute migraine headache that lasts 72 hours or longer.

No more than 10 mg per 24 hour period.

General dosage advice

Always take antimigraine drugs exactly as directed. Never take larger or more frequent doses, and do not take the drug for longer than directed.

If possible, lie down and relax in a dark, quiet room for a few hours after taking the medicine.

Precautions

These drugs should be used only to treat the type of headache for which they were prescribed. Patients should not use them for other headaches, such as those caused by stress or too much alcohol, unless directed to do so by a physician.

Anyone whose headache is unlike any previous headache should check with a physician before taking these drugs. If the headache is far worse than any other, emergency medical treatment should be sought immediately.

Taking too much of the antimigraine drug ergotamine (Cafergot), can lead to ergot poisoning. Symptoms include headache, muscle pain, numbness, coldness, and unusually pale fingers and toes. If not treated, the condition can lead to gangrene (tissue death).

Sumatriptan (Imitrex), naratriptan (Amerge), rizatriptan (Maxalt) and zolmitriptan (Zomig) may interact with ergotamine. These drugs should not be taken within 24 hours of taking any drug containing ergotamine.

Some antimigraine drugs work by tightening blood vessels in the brain. Because these drugs also affect blood vessels in other parts of the body, people with coronary heart disease, circulatory problems, or high blood pressure should not take these medicines unless directed to do so by their physicians.

About 40% of all migraine attacks do not respond to treatment with triptans or any other medication. If the headache lasts longer than 72 hours—a condition known as status migrainosus—the patient may be given narcotic medications to bring on sleep and stop the attack. Patients with status migrainosus are often hospitalized because they are likely to be dehydrated from severe nausea and vomiting.

Special conditions

People with certain other medical conditions or who are taking certain other medicines can have problems if they take antimigraine drugs. Before taking these drugs, be sure to let the physician know about any of these conditions:

ALLERGIES. Anyone who has had unusual reactions to ergotamine, caffeine, sumatriptan, zolmitriptan, or other antimigraine drugs in the past should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances.

PREGNANCY. Women who are pregnant should not take ergotamine (Cafergot). The effects of other antimigraine drugs during pregnancy have not been well studied. Any woman who is pregnant or plans to become pregnant should let her physician know before an antimigraine drug is prescribed.

BREASTFEEDING. Some antimigraine drugs can pass into breast milk and may cause serious problems in nursing babies. Women who are breastfeeding should check with their physicians about whether to stop breastfeeding while taking the medicine.

OTHER MEDICAL CONDITIONS. Before using antimigraine drugs, people with any of these medical problems should make sure their physicians know about their conditions:

• Coronary heart disease
• Angina (crushing chest pain)
• Circulatory problems or blood vessel disease
• High blood pressure
• Liver problems
• Kidney problems
• Any infection
• Eye problems.

USE OF CERTAIN MEDICINES. Taking antimigraine drugs certain other drugs may affect the way the drugs work or may increase the chance of side effects.

Side effects

The most common side effects are fluid retention, flushing; high blood pressure; unusually fast or slow heart rate; numbness; tingling; itching; nausea; vomiting; weakness; neck or jaw pain and stiffness; feelings of tightness, heaviness, warmth, or coldness; sore throat; and discomfort of the mouth and tongue.

More serious side effects are not common, but they may occur. If any of the following side effects occur, call a physician immediately:

• Tightness in the chest
• Bluish tinge to the skin
• Cold arms and legs

• Signs of gangrene, such as coldness, dryness, and a shriveled or black appearance of a body part
• Dizziness
• Drowsiness
• Shortness of breath or wheezing
• Skin rash
• Swelling of the eyelids or face.

Possible side effects with anticonvulsants include dizziness, drowsiness, emotional upset, skin rash, temporary hair loss, nausea, and irregular menstrual periods.

Other side effects may occur with any antimigraine drug. Anyone who has unusual symptoms after taking this medicine should get in touch with his or her physician.

Alternative treatments

There are two herbal remedies that are reported to be effective as alternative treatments for migraine. One is feverfew (Tanacetum parthenium ), an herb related to the daisy that is traditionally used in England to prevent migraines. Published studies indicate that feverfew can reduce the frequency and intensity of migraines. It does not, however, relieve pain once the headache has begun. The other herbal remedy is butterbur root (Petasites hybridus ). Petadolex is a natural preparation made from butterbur root that has been sold in Germany since the 1970s as a migraine preventive. Petadolex has been available in the United States since December 1998.

Interactions

Antimigraine drugs may interact with other medicines. When this happens, the effects of one or both of the drugs may change, or the risk of side effects may be greater. Anyone who takes these drugs should let the physician know all other medicines he or she is taking. Among the drugs that may interact with antimigraine drugs are:

• Beta blockers such as atenolol (Tenormin) and propranolol (Inderal)
• Drugs that tighten blood vessels such as epinephrine (EpiPen) and pseudoephedrine (Sudafed)
• Nicotine such as cigarettes or Nicoderm, Habitrol, and other smoking-cessation drugs
• Certain antibiotics, such as erythromycin and clarithromycin (Biaxin)
• Monoamine oxidase inhibitors such as phenelzine (Nardil) and tranylcypromine (Parnate)
• Certain antidepressants, such as sertraline (Zoloft), fluoxetine (Prozac), and paroxetine (Paxil)
• Fluvoxamine (Luvox), prescribed for obsessive compulsive disorder or chronic pain.

Anticonvulsants should not be taken together with aspirin, alcohol, or tranquilizers.

Remember naratriptan, sumatriptan, rizatriptan and zolmitriptan may interact with ergotamine. These drugs should not be taken within 24 hours of taking any drug containing ergotamine.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., revised. Washington, DC: American Psychiatric Association, 2000.

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Headache." Section 14, Chapter 168 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Psychogenic Pain Syndromes." Section 14, Chapter 167 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II. "CAM Therapies for Specific Conditions: Headache." New York: Simon & Schuster, 2002.

PERIODICALS

Ceballos Hernansanz, M. A., R. Sanchez Roy, A. Cano Orgaz, et al. "Migraine Treatment Patterns and Patient Satisfaction with Prior Therapy: A Substudy of a Multicenter Trial of Rizatriptan Effectiveness." Clinical Therapeutics 25 (July 2003): 2053-2069.

Corbo, J. "The Role of Anticonvulsants in Preventive Migraine Therapy." Current Pain and Headache Reports 7 (February 2003): 63-66.

Dodick, D. W. "A Review of the Clinical Efficacy and Tolerability of Almotriptan in Acute Migraine." Expert Opinion in Pharmacotherapy 4 (July 2003): 1157-1163.

Dowson, A. J., and B. R. Charlesworth. "Patients with Migraine Prefer Zolmitriptan Orally Disintegrating Tablet to Sumatriptan Conventional Oral Tablet." International Journal of Clinical Practice 57 (September 2003): 573-576.

Johannessen, C. U., and S. I. Johannessen. "Valproate: Past, Present, and Future." CNS Drug Review 9 (Summer 2003): 199-216.

Sahai, Soma, MD, Robert Cowan, MD, and David Y. Ko, MD. "Pathophysiology and Treatment of Migraine and Related Headache." eMedicine April 30, 2002.

Tepper, S. J., and D. Millson. "Safety Profile of the Triptans." Expert Opinion on Drug Safety 2 (March 2003): 123-132.