Antimigraine medications are drugs that are given to lower the risk of a severe migraine attack or to reduce the severity of the headache once an attack begins.
Purpose
Treatment that is given to stop or ease the pain of a migraine headache after it has started is known as acute or abortive treatment.
Preventive treatment for migraine headaches is called migraine prophylaxis or prophylactic therapy. Prophylactic medications are taken when the patient is not having a headache. They have three purposes:
lower the frequency and severity of the patient's headaches
make acute migraines more responsive to abortive treatment
improve the patient's overall quality of life
Not all patients with migraines need prophylactic treatment. Most doctors, however, recommend prophylactic medications in the following circumstances:
The patient has two or more migraines per month, with disability lasting three or more days
Acute treatment is contraindicated or is ineffective
The patient has been using abortive medications more than twice a week
The patient has a complex form of migraine such as hemiplegic or basilar migraine
The patient is at risk of permanent neurologic injury from acute attacks
Abortive medications
The following interactions have been reported for abortive medications:
Triptans: All the triptans narrow coronary arteries by 10–20% and will intensify the effects of other vasoconstrictive drugs, including the ergot alkaloids and drugs given for vascular disorders. With the exception of naratriptan, the triptans cannot be taken together with MAO inhibitor antidepressants because of the risk of a rapid and dangerous rise in blood pressure. Rizatriptan has been reported to interact with the beta-blockerpropranolol.
Ergot alkaloids: Cannot be taken together with the triptans. Ergot alkaloids should not be taken together with methysergide because of an additive effect. Should not be taken together with other vasoconstrictive drugs (including beta-blockers, some acid-reducing drugs, some antibiotics, and some antifungal drugs) because of the increased risk of gangrene.
NSAIDs: These drugs tend to prolong bleeding time and should be used cautiously by patients taking blood-thinning medications. Alcoholic beverages increase the risk of gastric ulcers or bleeding from the use of NSAIDs. In addition, patients should not take more than one NSAID at a time.
Combination analgesics: These drugs should not be used together with MAO inhibitors or other drugs that contain acetaminophen. They will intensify the actions of other drugs that may cause drowsiness, including alcohol, TCAs, antihistamines, sedatives, and muscle relaxants.
Antiemetics: Should not be taken together with alcohol (intensifies central nervous system depression), tricyclic antidepressants (lowers blood pressure), or phenobarbital. Patients taking anticonvulsants may need to have their dosage increased if they are given an antiemetic.
Prophylactic medications
The following interactions have been reported for prophylactic medications:
Beta-blockers: Antacids decrease the absorption of beta-blockers. Cimetidine is reported to intensify the actions of beta-blockers. Beta-blockers may interact with insulin or other diabetes medications to produce high blood sugar levels. They should not be taken together with MAO inhibitors because of the risks of severe high blood pressure. Cocaine also increases the risks of high blood pressure or other heart problems in patients taking beta-blockers.
TCAs: Should not be taken together with barbiturates, alcohol, sleeping medicines, or sedatives because they intensify central nervous system depression. They may also intensify the effects of certain antibiotics and anti-fungal medications. They may interact with bupropion to produce seizures. TCAs should never be taken with MAO inhibitors or SSRIs because of the risk of serotonin syndrome, a potentially fatal condition marked by fever, rapid changes in blood pressure, sweating, hyperreactive reflexes, delirium, nausea, vomiting, and coma. Serotonin syndrome takes its name from the overly high levels of serotonin in the patient's nervous system that are produced by these drug combinations.
SSRIs: Should never be taken together with other anti-depressant medications because of the risk of serotonin syndrome. They may increase the patient's drowsiness if taken together with antihistamines, sleep medications, opioidanalgesics, and muscle relaxants. Patients taking insulin or other diabetes medications may need to have their dosage adjusted if they are also taking an SSRI. SSRIs should not be taken together with herbal preparations used as mild tranquilizers, particularly compounds containing valerian or St. John's wort.
Serotonin antagonists: Methysergide should not be taken together with ergot alkaloids or triptans because it intensifies their vasoconstrictive action. Patients taking this drug should give up smoking for the same reason. In addition, methysergide has been reported to counteract the pain-relieving effectiveness of opioid analgesics.
Complementary and alternative medications (CAM)
There are two herbal preparations used as migraine preventives as of 2004. Feverfew (Tanacetum parthenium) is an herb related to the daisy that is traditionally used in England for migraine prophylaxis. Feverfew contains a compound called parthenolide, which is thought to counteract the inflammatory reaction in the cerebral blood vessels that precedes an acute migraine attack.
The second herb is butterbur root (Petasites hybridus), which is the active ingredient in Petadolex, a preparation that has been sold in Germany since the 1970s as a migraine preventive. Petadolex has been available in the United States since December 1998. Butterbur root contains compounds known as petasines, which relieve inflammation as well as counteract the spasmodic contraction of blood vessels that occurs during a migraine attack. Researchers reported in 2003 that Petadolex reduced the frequency of migraine attacks in subjects in a multicenter trial by 60%. The butterbur root preparation has fewer and milder side effects than conventional prophylactic drugs; it also appears to be safe for children and adolescents.
It should be noted that, contrary to the popular notion, herbals are drugs that can and do cause side effects; they are not the medical "free ride" many people seem to think they are. They should thus be used with care and caution and in consultation with a physician.
CAM preparations
Feverfew should not be used with anticoagulants (blood thinners), as it intensifies their effects. It may also interfere with the body's absorption of iron. NSAIDs reduce the effectiveness of feverfew. No interactions with prescription drugs have been reported for butterbur root preparations.
Diagnosis
Migraine headaches are classified by the International Headache Society (IHS) as primary headaches, which means that they are not caused by other diseases or disorders. Severely painful headaches, however, are not necessarily migraines and may be caused by other conditions, some of them potentially life-threatening. Headaches caused by other disorders are known as secondary headaches. They may be associated with space-occupying brain tumors, meningitis, stroke, head trauma, pain referred from the neck or jaw, or a ruptured aneurysm inside the head. Patients with any of the following signs or symptoms should be carefully evaluated, including those who have been previously diagnosed with and treated for migraines:
The patient is not responding to appropriate treatment for the headaches.
The headache is severe and is sudden in onset. Although a small percentage of patients with migraines have what are called "crash" or "thunderclap" migraines, most migraine headaches build up slowly over a period of one or two hours.
The headache differs from the usual pattern of the patient's migraines.
The patient has described the present headache as "the worst ever."
The patient has abnormal neurological signs or symptoms such as a swollen optic disk (papilledema), seeing double, loss of sensation, or alteration of consciousness.
Some patients may be suffering from another type of primary headache in addition to migraines. It is possible, for example, for people to have both chronic tension headaches and migraines, and each type may require separate treatment.
A third consideration is whether the patient has been diagnosed with any comorbid disorders. The doctor must take such conditions as hypertension, depression, epilepsy, heart problems, and other disorders into account when selecting antimigraine medications for the patient.
Patient education
Effective use of antimigraine drugs depends on good communication between the patient and the doctor. Migraine headaches vary considerably in their frequency, severity, and associated symptoms; in addition, people vary in their responses to a given medication. It may take some months of trial and error to work out the best treatment regimen for an individual patient with respect to the specific drugs used and their dosage levels. Patients should be advised to give each medication a fair trial (usually about two months) before deciding that the drug does not work for them. In addition, they should be told that some drugs—particularly the beta-blockers—must be taken for several months before the patient can expect to see results. Finally, patients who are taking abortive medications or opioidanalgesics should be warned about the risks of dependence or rebound headaches from overuse of these drugs.
Rebound headaches
Rebound headaches are also known as analgesic abuse headaches. They result from overuse of abortive drugs, most commonly the ergot alkaloids. According to one survey of primary care physicians, about 20% of patients treated for migraine experience rebound headaches. These headaches have the following characteristics:
They occur every day or almost every day.
They are brought on by a very low level of physical or intellectual activity.
The patient has been using abortive migraine medications more than two days a week.
The patient has been using the medications above the recommended dosage level.
The patient develops withdrawal symptoms if the medications are stopped abruptly.
The headaches are accompanied by restlessness, depression, irritability, difficulty concentrating, or memory problems.
Status migrainosus
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 populations
CHILDREN Migraines in children are not unusual; a study published in 2003 reported that 10% of children between the ages of six and 20 suffer from migraines, and that they lose, on average, almost two more weeks of school each year than their classmates. Treatment of children's migraines, however, is complicated by the fact that most effective medications—whether abortive or prophylactic—have not been adequately evaluated for use in children or are not recommended for children. As of late 2003, however, there have been few rigorous studies of antimigraine drugs in children; much more research is needed in this area. Cyproheptadine, which is the drug most often prescribed for children's migraines, is not always effective; preventive therapy with propranolol, one of the tricyclics, or an anticonvulsant medication appears to be safe as well as effective in children and adolescents.
PREGNANCY AND LACTATION Pregnancy and lactation complicate migraine treatment in that many antimigraine drugs should not be taken by pregnant or nursing women. These include the ergot alkaloids, anticonvulsants, tricyclic antidepressants, methysergide, and the SSRIs. In addition, NSAIDs should not be used during the last trimester of pregnancy.
OLDER ADULTS Some antimigraine medications are not recommended for patients over the age of 60–65, particularly the triptans and the ergot alkaloids. Older adults may also be more susceptible to the side effects of NSAIDs and TCAs.
Patient dissatisfaction
Antimigraine medications as a group have a high rate of reported patient complaints. One reason is the high cost of some of these drugs; another is dosing difficulties. One survey of migraine patients reported the following reasons for discontent with drug therapy: pain relief took too long (87%); pain was only partly relieved (84%); the medication sometimes failed to work (84%); headache returned within a day (71%); the drug had too many side effects (35%). Because of the limitations of antimigraine medications, many doctors advise their patients to supplement drug therapy with such other measures as adequate sleep and exercise, a low-fat diet, quitting smoking, stress management techniques, or cognitive-behavioral psychotherapy.
It is also worth noting that managed care (the health insurance industry) accounts for some patient dissatisfaction. Most health plans strictly limit coverage to an "average" number of doses of triptans per month. Patients who need more doses either must have their doctors try to get the insurance company to authorize them, or the patients must pay the full price of the extra medication themselves.
It is possible that new ways of thinking about migraine will lead to improved antimigraine medications in the future. Migraine headaches are no longer regarded as "just headaches," but as features of a largely inherited chronic disorder that increases the risk of long-term damage to the brain. The use of MRIs and other new imaging techniques may eventually answer some unresolved questions about effective migraine treatment.
Interactions
Patients who are taking any antimigraine drug should make sure to give the doctor a list of all other medications that they take on a regular basis, including over-the-counter pain relievers, herbal preparations, and any special herbal or medicinal teas or extracts.
BOOKS
"Headache." Section 14, Chapter 168 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. 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.
"Psychogenic Pain Syndromes." Section 14, Chapter 167 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.
Wilson, Billie Ann, RN, PhD, Carolyn L. Stang, PharmD, and Margaret T. Shannon, RN, PhD. Nurses Drug Guide 2000. Stamford, CT: Appleton and Lange, 1999.
PERIODICALS
Corbo, J. "The Role of Anticonvulsants in Preventive Migraine Therapy." Current Pain and Headache Reports 7 (February 2003): 63–66.
Freitag, F. G. "Preventative Treatment for Migraine and Tension-Type Headaches: Do Drugs Having Effects on Muscle Spasm and Tone Have a Role?" CNS Drugs 17 (2003): 373–381.
Kalin, P. "The Common Butterbur (Petasites hybridus)—Portrait of a Medicinal Herb." [in German] Forschende Komplementarmedizin und klassische Naturheilkunde 10 (April 2003) (Suppl. 1): 41–44.
Kruit, Mark C., MD, Mark A. van Buchem, MD, PhD, Paul A. M. Hofman, MD, PhD, et al. "Migraine as a Risk Factor for Subcortical Brain Lesions." Journal of the American Medical Association 291 (January 28, 2004): 427–434.
Malapira, Amelito, MD, and Jorge Mendizabal, MD. "Migraine Headache." eMedicine 22 September 2003 (May 9, 2004). <http://www.emedicine.com/neuro/topic218.htm>.
Punay, Nestor C., MD, and James R. Couch, MD, PhD. "Antidepressants in the Treatment of Migraine Headache." Current Pain and Headache Reports 7 (February 2003): 51–54.
Sahai, Soma, MD, Robert Cowan, MD, and David Y. Ko, MD. "Pathophysiology and Treatment of Migraine and Related Headache." eMedicine 30 April 2002 (May 9, 2004). <http://www.emedicine.com/neuro/topic517.htm>.
Silberstein, S. D., and P. J. Goadsby. "Migraine: Preventive Treatment." Cephalalgia 22 (September 2002): 491–512.
Tepper, S. J., and D. Millson. "Safety Profile of the Triptans." Expert Opinion on Drug Safety 2 (March 2003): 123–132.
Victor, S., and S. Ryan. "Drugs for Preventing Migraine Headaches in Children." Cochrane Database System Review 4 (2003): CD002761.
Waeber, C. "Emerging Drugs in Migraine Treatment." Expert Opinion on Emerging Drugs 8 (November 2003): 437–456.
