Antimigraine medications

Definition

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

Description

Abortive medications

Abortive medications for migraine are prescribed according to the severity of the patient's headaches, the presence of nausea or vomiting, the patient's response to the drug, and the presence of such comorbid conditions as depression or epilepsy . With the exception of mild analgesics, however, these drugs cannot be used as preventive treatment; they are taken only when an acute attack begins. Abortive medications are categorized into four major groups.

SELECTIVE SEROTONIN RECEPTOR (5-HT1) AGONISTS Selective serotonin receptor agonists have been used to treat migraines since 1991. They work by activating serotonin receptors in the brain, which block an inflammatory process that affects the blood vessels in the head and leads to a leakage of blood plasma through the vessel walls. Some researchers think that the serotonin receptor agonists also reduce the pain of migraine by slowing down the firing of nerve cells in pain-sensitive parts of the head. These drugs, which are also known as triptans or 5-hydroxytryptamine 1B agonists, are effective in treating about 70% of migraine patients. Sumatriptan (Imitrex) is the prototype of this class of medications.

Second-generation triptans include such drugs as eletriptan (Relpax), naratriptan (Amerge), rizatriptan (Maxalt), almotriptan (Axert), frovatriptan (Frova), and zolmitriptan (Zomig). The second-generation triptans were developed to increase the speed of the drug's absorption through the digestive tract and thus relieve the patient's pain more rapidly. All the triptans are prescribed for moderately severe or severe migraines; one, sumatriptan, is available as a nasal spray or injection for patients with severe vomiting. One major drawback of the triptans, however, is that moderate-to-severe headache pain tends to recur within 24 hours of the first dose.

ERGOT ALKALOIDS Ergot alkaloids are an older group of drugs that include such compounds as ergotamine tartrate (Ergostat) and dihydroergotamine (DHE-45, Migranal). These drugs are derived from ergot, a compound produced by a fungus (Claviceps purpurea ) that grows on rye plants. The medications work by causing the blood vessels in the head to constrict or narrow, which counteracts the dilation of the blood vessels that causes pain. Some medications in this group are combinations of ergotamine tartrate and caffeine (Cafergot, Ercaf); the caffeine intensifies the vasoconstrictive effect of the alkaloid. Like the triptans, the ergot alkaloids are used to treat moderate-to-severe migraines. They are not prescribed as frequently as they once were, however, because of the severity of their side effects and because they cannot be given to patients with coronary artery disease or other vascular disorders.

ANALGESICS Analgesics in general are medications given to relieve pain. These drugs are used to treat patients who have infrequent migraine headaches, or who cannot be treated with triptans. There are two main types of analgesics used as acute treatment for migraines, nonsteroidal anti-inflammatory drugs, or NSAIDs, and combination analgesics. NSAIDs include aspirin, naproxen (Naprosyn), diclofenac (Voltaren, Cataflam), ibuprofen (Advil, Motrin), flurbiprofen (Ansaid), ketorolac (Toradol), and ketoprofen (Orudis). Combination analgesics include butalbital plus acetaminophen (Fioricet), butalbital plus aspirin (Fiorinal), and isometheptene plus acetaminophen and dichloralphenazone (Midrin).

As of 2004, doctors disagree about the use of opioid (drugs that are or act like narcotics) analgesics to treat migraine pain. On the one hand, opioids are stronger painkillers than NSAIDs or butalbital. On the other hand, they often make the patient quite drowsy or sedated, and they have a high potential for overuse and dependence. Most doctors, however, consider opioids combined with other analgesics—for example, compounds such as oxycodone plus acetaminophen (Percocet) or aspirin with codeine—to be safe for patients with infrequent migraines who can rest if they feel drowsy. Some doctors will prescribe a synthetic opioid known as butorphanol in the form of a nasal spray (Stadol NS) for use as rescue therapy if the patient's usual abortive drug fails to stop an acute attack; this spray, however, is habit forming and is presently classified as a controlled drug.

ANTIEMETICS Antiemetics are medications given to stop vomiting. These may be beneficial if the patient's headaches are often accompanied by nausea and vomiting. The doctor may also prescribe them to enhance the absorption of other medications taken by mouth, because migraines cause the digestive tract to slow down. The most common antiemetics prescribed for migraine patients are droperidol (Inapsine), metoclopramide (Reglan), and prochlorperazine (Compazine). Prochlorperazine can be given intravenously, by rectal suppositories, or by intra-muscular injection if the patient cannot take the drug by mouth.

Prophylactic medications

There are seven major categories of drugs given for migraine prophylaxis.

ANTICONVULSANTS Anticonvulsants , which are also called antiepileptic drugs , are considered first-line preventive treatment for migraine. These drugs work by enhancing the neurotransmission of gamma amino-butyric acid, or GABA. GABA is an amino acid that slows down or inhibits the transmission of nerve impulses in the central nervous system . Valproic acid (Depakote, divalproex sodium) is the most commonly used anticonvulsant in migraine treatment, and has been shown to reduce migraine frequency by 50%.

Other anticonvulsants that have been used in migraine prophylaxis are gabapentin (Neurontin) and topiramate (Topamax). Both drugs are reported to be effective in 50–55% of migraine patients.

BETA-BLOCKERS Beta-blockers are widely prescribed as migraine prophylaxis; they are reported to help 50–70% of patients. The only beta-blockers that have been approved by the Food and Drug Administration (FDA) for migraine therapy, however, are propranolol (Inderal) and timolol (Blocadren). Other beta-blockers that have been used to treat migraines without FDA approval include nadolol (Corgard), atenolol (Tenormin), and metoprolol (Lopressor, Toprol-XL). It is thought that these drugs reduce the frequency of migraines by preventing the blood vessels in the head from dilating and by increasing the release of oxygen to the surrounding tissues. It takes about two months of treatment, however, for patients to benefit from beta-blockers.

CALCIUM CHANNEL BLOCKERS The most common drug in this category used in preventive treatment is vera-pamil (Calan, Covera, Verelan). Studies of the effectiveness of verapamil, however, have shown mixed results. It appears to be most useful in treating patients who cannot take beta-blockers or have been diagnosed with coexisting hypertension.

TRICYCLIC ANTIDEPRESSANTS (TCAS) The tricyclic antidepressants are another group of drugs used in migraine prophylaxis. Amitriptyline (Elavil) has been shown in well-conducted studies to benefit migraine patients, although doxepin (Sinequan), nortriptyline (Aventyl), and protriptyline (Vivactil, Triptil) have also been used for preventive treatment. TCAs are often given to patients who are suffering from insomnia or depression as well as migraine. Their chief drawback is their long-term side effects, particularly weight gain.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) These drugs are not as effective for migraine prophylaxis as the tricyclic antidepressants, but a few small-scale studies have shown that they benefit some patients. The SSRIs include such drugs as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil).

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) Nonsteroidal anti-inflammatory medications can be used for migraine prophylaxis as well as abortive treatment; however, these drugs have a higher risk of adverse effects—particularly in the digestive tract—when they are used preventively.

SEROTONIN ANTAGONISTS Methysergide (Sansert) is a synthetic ergot alkaloid that has been used as prophylactic treatment; its primary disadvantage is the number and severity of possible side effects. Cyproheptadine (Periactin), an antihistamine, is sometimes used for migraine prophylaxis in children even though there is little evidence of its effectiveness.

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.

Recommended dosage

Abortive medications

Abortive medications are taken at the first sign of a migraine attack. About 20% of migraine patients have headaches preceded by an aura, or brief period of warning symptoms that may include seeing flashing or shimmering lights, temporary loss of vision, difficulty speaking, weakness in an arm or leg, or tingling sensations in the face or hands. Most patients with migraines, however, do not have auras but experience the headache pain as building gradually over an hour or two. Abortive medications include triptans, ergot alkaloids, NSAIDs, combination analgesics, and antiemetics.

TRIPTANS Sumatriptan is available as a nasal spray or injection as well as in tablet form; the other triptans are available only as tablets. (Sumatriptan should be injected only into the areas the manufacturer recommends; that is, injections into the arms are not recommended because they are much more painful than injections into thighs, the recommended site.) The patient may take 25–100 mg of sumatriptan by mouth at the beginning of an attack, with a second dose of up to 100 mg after two hours. Additional doses may be taken at two-hour intervals, up to 300 mg daily. With the nasal spray, 5–20 mg may be inhaled into one nostril, with a second dose after two hours if the headache returns. Injections of sumatriptan contain 6 mg per dose and may be given twice, at least one hour apart. With zolmitriptan, the initial dose is 2.5–5 mg by mouth, with a second dose at any time after two hours following the first dose; the maximum daily dose is 10 mg. The initial dose of naratriptan is 2.5 mg, which can be repeated four hours after the first dose. Rizatriptan is taken by mouth in an initial dose of 5–10 mg, which may be repeated every two hours up to a maximum daily dose of 30 mg. Almotriptan is taken in an initial dose of 6.25–12.5 mg, which may be repeated only once. Frovatriptan is taken only once, in a dose of 2.5 mg at the beginning of the headache. Eletriptan is taken in an initial dose of 20–40 mg, which may be repeated once after two hours; the maximum daily dose is 80 mg.

ERGOT ALKALOIDS Ergotamine tartrate is taken by mouth in a 1 mg tablet at the beginning of the attack, with additional doses every 30 minutes as needed; total dosage must not exceed 6 mg per attack. Rectal suppositories containing 1–2 mg of the drug may be used at the onset of the headache and repeated every half hour, not to exceed 4 mg per attack. Dihydroergotamine mesylate (DHE-45) may be given by injection in an initial dose of 0.5–1 mg, to be repeated at hourly intervals up to a maximum dose of 3 mg. The drug may also be given intravenously for more rapid relief.

NSAIDS The patient may take an initial dose of 900–1,000 mg of aspirin, with the dose repeated every 1–2 hours as needed. Ibuprofen may be taken by mouth in an initial dose of 400–1,200 mg, to be repeated with a second dose of 400–800 mg in 1–2 hours. The maximum daily dose of ibuprofen is 3,200 mg. Naproxen may be taken in an initial dose of 825 mg, with additional doses of 550 mg after 1–2 hours as needed. Ketorolac may be taken in 10 mg doses every four hours, not to exceed 40 mg per day. Ketorolac should not be used for longer than five days.

COMBINATION ANALGESICS Fiorinal may be taken in an initial dose of 1–2 tablets by mouth every four hours as needed, up to six tablets per day. Midrin is taken in an initial dose of two capsules, then one capsule every hour until the headache is relieved; not to exceed five capsules in a 12-hour period.

ANTIEMETICS Droperidol is given by injection in a dose of 2.5–10 mg. Metoclopramide is given by mouth or by injection in a dose of 10–20 mg. Prochlorperazine may be taken by mouth in a dose of 5–10 mg every 4–6 hours; by injection in a dose of 5–10 mg every 3–4 hours up to a maximum dose of 40 mg per day; or by rectal suppositories in a dose of 25 mg twice a day.

Prophylactic medications

Dosages for these medications vary somewhat depending on the individual patient's response. The general principle of management is to begin with the lowest effective dose of the particular drug, increasing it gradually until the patient begins to benefit or until the maximal safe dose is reached.

ANTICONVULSANTS Valproic acid is given in an initial dose of 150–250 mg per day, gradually increasing to a maximum dose of 1,500 mg per day. Gabapentin is given in an initial dose of 300 mg per day, gradually increasing up to a maximum dose of 2,400 mg per day.

BETA-BLOCKERS Beta-blocker doses are as follows:

• propranolol: initial dose of 40 mg twice a day, up to a maximum of 320 mg per day
• timolol: 10 mg per day initially, maximum daily dose 30 mg
• nadolol: 20 mg four times per day initially, up to a maximum of 240 mg per day
• metoprolol: 50 mg twice a day initially, not to exceed 200 mg per day

CALCIUM CHANNEL BLOCKERS Verapamil is given in an initial dose of 40 mg three times a day; maximal daily dose is 480 mg.

TCAS Amitriptyline, doxepin, and nortriptyline are given by mouth at bedtime in an initial dose of 10–25 mg, with the dose increased by 10–25 mg every two weeks up to a maximum dose of 150–175 mg. Protriptyline is given in an initial dose of 15 mg, up to a maximum daily dose of 40 mg.

SSRIS Fluoxetine is taken on waking in an initial dose of 10 mg, which may be increased every two weeks up to a maximum daily dose of 60 mg. Sertraline may be given in an initial dose of 50 mg per day, increased at weekly intervals up to a daily dose of 200 mg. Paroxetine may be started at a dose of 10 mg per day and gradually increased up to a daily dose of 50 mg.

NSAIDS Naproxen may be taken in a dose of 275 mg three times daily or a dose of 550 mg twice daily.

SEROTONIN ANTAGONISTS Methysergide is given in a daily dose of 2 mg per day, gradually increasing to a maximum of 8 mg per day. Cyproheptadine is given in an initial dose of 2 mg, increasing every three days to a maintenance dose of 8–32 mg per day.

CAM preparations

The recommended dosage of feverfew as a migraine preventive is 125 mg daily of freeze-dried powdered leaf; patients should start out with a lower dose and work up gradually to 125 mg. The dried leaf is available in capsule form. Petadolex is sold as soft gelatin 50-mg capsules. The recommended dose for migraine prophylaxis is 150 mg daily for adults and 50–100 mg daily for children and adolescents.

Precautions

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 opioid analgesics 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.

Side effects

Abortive medications

In addition to the risk of rebound headaches, possible side effects of abortive medications include:

• Triptans: May cause tingling, numbness, sensations of heat or flushing, dizziness , drowsiness, or pain at the injection site.
• Ergot alkaloids: May cause nausea, vomiting, diarrhea, weakness, itching, cold skin, thirst, tingling sensations, and severe muscle cramps; also may cause severe rebound headaches. The most serious potential side effect of ergot alkaloids, however, is gangrene—the death of tissue in the fingers or toes due to constriction of the smaller blood vessels and loss of blood supply to the tissue.
• NSAIDs: May cause heartburn, nausea, and vomiting; may also cause drowsiness, dry mouth, or mild depression.
• Combination analgesics: Midrin has been reported to cause temporary dizziness and skin rashes. The most common side effects of Fioricet and Fiorinal include lightheadedness, nausea, and sleep disturbances. Also, the narcotics and barbiturates (Fiorinal) have the potential for drug abuse and dependence.
• Antiemetics: May cause anxiety, dizziness, low blood pressure, sedation, nausea, dry mouth, and restlessness.

Prophylactic medications

The following side effects have been reported for prophylactic medications:

• Anticonvulsants: Valproic acid may cause indigestion and vomiting, but hair loss, weight gain, tremor, hallucinations, and liver damage have also been reported. Gabapentin and topiramate are associated with drowsiness, dizziness, tingling sensations, diarrhea, altered taste, and fatigue .
• Beta-blockers: May cause dizziness, fatigue, nausea, memory problems, sexual dysfunction, bradycardia (slowed heartbeat), and hallucinations.
• Calcium channel blockers: May cause low blood pressure and constipation; in addition, the headaches may grow worse for the first few weeks of treatment.
• TCAs: May cause dry mouth, constipation, difficulty urinating, increased appetite, loss of sexual desire, heavy sweating, agitation, tremor, and seizures .
• SSRIs: May cause loss of appetite or sexual desire, anxiety, drowsiness, nausea, or flulike symptoms.
• NSAIDs: More likely to cause digestive problems when used for prophylaxis than when used for acute treatment.
• Serotonin antagonists: Methysergide has been reported to cause insomnia, abdominal pain, diarrhea, nausea, heartburn, increased sensitivity to cold, and depression. Cyproheptadine may cause dry mouth, increased appetite, and weight gain.

CAM preparations

Feverfew should not be used by pregnant women because it may stimulate uterine contractions. It may also cause mild acid indigestion in some people. Patients who use fresh plant leaves rather than standardized preparations may experience mouth ulcers or temporary loss of taste. Also, patients who use fresh plant leaves cannot regulate their doses: one time they may get too much of the drug and another time not enough.

The side effects reported for preparations made from butterbur root are rare, but include an unpleasant taste in the mouth, belching, and a mild skin rash in some patients.

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.

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-blocker propranolol.
• 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:

• Anticonvulsants: Valproic acid will intensify the effects of other anticonvulsants, barbiturates, alcohol, and anti-depressants. It interacts with aspirin and heparin to increase the risk of spontaneous bleeding. Gabapentin intensifies the effects of morphine, but is less effective when taken together with antacids.
• 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.
• Calcium channel blockers: Verapamil may cause low blood pressure or dizziness if taken together with alcohol. It should not be taken with beta-blockers because of a risk of congestive heart failure or slowed heartbeat. Verapamil also intensifies the effects of cyclosporine and lithium.
• 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, opioid analgesics, 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.

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.

Resources

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

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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.

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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.

OTHER

Cleveland Clinic Health System. "Migraines in Children and Adolescents." (May 9, 2004.) <http://www.cchs.net/health/healthinfo/docs/2500/2555.asp?index=9637>.

NINDS. "Migraine Information Page." NINDS, 2003 (May 9, 2004). <http://www.ninds.nih.gov/health_and_medical/pubs/migraineupdate.htm>.

ORGANIZATIONS

American Council for Headache Education (ACHE). 19 Mantua Road, Mt. Royal, NJ 08061. (856) 423-0258; Fax: (856) 423-0082. [email protected]. <http://www.achenet.org>.

International Headache Society (IHS). Oakwood, 9 Willowmead Drive, Prestbury, Cheshire SK10 4BU, United Kingdom. +44 (0) 1625 828663; Fax: +44 (0) 1625 828494. [email protected]. <http://216.25.100.131>.

National Headache Foundation. 820 North Orleans, Suite 217, Chicago, IL 60610. (773) 525-7357 or (888) NHF-5552. <http://www.headaches.org>.

U. S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA (463-6332). <http://www.fda.gov>.

Rebecca Frey, PhD