Prophylactic medications are medications taken daily to reduce the frequency and duration of migraine headaches. They are not taken once a headache has begun. There are several classes of prophylactic medications:
- beta blockers,
- calcium-channel blockers,
- tricyclic antidepressants,
- antiserotonin agents, and
- anticonvulsants.
Medications with the longest history of use are propranolol (Inderal), a beta blocker, and amitriptyline (Elavil, Endep), an antidepressant. When choosing a prophylactic medication for a patient the doctor must take into account side effects of the drug, drug-drug interactions, and co-existing conditions such as diabetes, heart disease, and high blood pressure.
Beta blockers
Beta-blockers are a class of drugs that block the effects of beta-adrenergic substances produced by the body, specifically the nerves and the adrenal gland, such as adrenaline (epinephrine). By blocking the effects of adrenaline, beta-blockers relieve stress on the heart by slowing the rate at which the heart beats. Beta-blockers have been used to treat high blood pressure, angina, certain types or tremors, stage fright, and abnormally fast heart beats (palpitations). They also have become important drugs for improving survival after heart attacks. Beta-blockers have been used for many years to prevent migraine headaches.
It is not known how beta-blockers prevent migraine headaches. It may be by decreasing prostaglandin production, though it also may be through their effect on serotonin or a direct effect on arteries. The beta-blockers used in preventing migraine headaches include propranolol (Inderal), atenolol (Tenormin), metoprolol (Lopressor, Lopressor LA, Toprol XL), nadolol (Corgard), and timolol (Blocadren).
Beta-blockers generally are well-tolerated. They can aggravate breathing difficulties in patients with asthma, chronic bronchitis, or emphysema. In patients who already have slow heart rates (bradycardias) and heart block (defects in electrical conduction within the heart), beta-blockers can cause dangerously slow heartbeats. Beta-blockers can aggravate symptoms of heart failure. Other side effects include drowsiness, diarrhea, constipation, fatigue, decrease in endurance, insomnia, nausea, depression, dreaming, memory loss, impotence.
Tricyclic antidepressants
Tricyclic antidepressants (TCAs) prevent migraine headaches by altering the neurotransmitters, norepinephrine and serotonin, that the nerves of the brain use to communicate with one another. The tricyclic antidepressants that have been used in preventing migraine headaches include amitriptyline (Elavil, Endep), nortriptyline (Pamelor, Aventyl), doxepin (Sinequan), imipramine (Tofranil), and protriptyline.
The most commonly encountered side effects associated with TCAs are fast heart rate, blurred vision, difficulty urinating, dry mouth, constipation, weight gain or loss, and low blood pressure when standing (orthostatic hypotension).
TCAs should not be used with drugs that inhibit monoamine oxidase such as isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane), since high fever, convulsions and even death may occur. TCAs are used with caution in peole with seizures, since they can increase the risk of seizures. TCAs also are used with caution in men with enlargement of the prostate because they can make urination difficult. TCAs can cause elevated pressure in the eyes in some glaucoma sufferers. TCAs can cause excessive sedation when used with other medications that slow the brain's processes, such as alcohol, barbiturates, narcotics, and benzodiazepines, for example, lorazepam (Ativan), diazepam (Valium), temazepam (Restoril), oxazepam (Serax), clonazepam (Klonopin), and zolpidem (Ambien). Epinephrine should not be used with amitriptyline, since the combination can cause severe high blood pressure
Antiserotonin medications
Methysergide (Sansert) prevents migraine headaches by constricting blood vessels and reducing inflammation of the blood vessels. Methylergonovine is related chemically to methysergide and has a similar mechanism of action. They are not widely used because of their side effects. The most serious side effect of methysergide is retroperitoneal fibrosis (scarring of tissue around the ureters that carry urine from the kidneys to the bladder). Retroperitoneal fibrosis, though rare, can block the ureters and cause backup of urine into the kidneys. Backup of urine into the kidneys can cause back and flank (the side of the body between the ribs and hips) pain and ultimately can lead to kidney failure. Methysergide also has been reported to cause scarring around the lungs that can lead to chest pain, shortness of breath, as well as scarring of the heart valves.
Calcium channel blockers
Calcium channel blockers (CCBs) are a class of drugs that block the entry of calcium into the muscle cells of the heart and the arteries. By blocking the entry of calcium, CCBs reduce contraction of the heart muscle, decrease heart rate, and lower blood pressure. CCBs are used for treating high blood pressure, angina, and abnormal heart rhythms (for example, atrial fibrillation). CCBs also appear to block the effects of a chemical within nerves, called serotonin, and have been used occasionally to prevent migraine headaches. The CCBs used in preventing migraine headaches are diltiazem (Cardizem, Dilacor, Tiazac), verapamil (Calan, Verelan, Isoptin), and nimodipine.
The most common side effects of CCBs are constipation, nausea, headache, rash, edema (swelling of the legs with fluid), low blood pressure, drowsiness, and dizziness. When diltiazem or verapamil are given to individuals with heart failure, symptoms of heart failure may worsen because these drugs reduce the ability of the heart to pump blood. Verapamil and diltiazem may reduce the elimination and increase the blood levels of carbamazepine (Tegretol), simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor). This can lead to toxicity from these drugs.
Anticonvulsants
Anticonvulsants (antiseizure medications) also have been used to prevent migraine headaches. Examples of anticonvulsants that have been used are valproic acid, phenobarbital, gabapentin, and topiramate. It is not known how anticonvulsants work to prevent migraine headaches.
Who should consider prophylactic medications to prevent migraine headaches?
Not all migraine sufferers need prophylactic medications; individuals with mild or infrequent headaches that respond readily to abortive medications do not need prophylactic medications. Individuals who should consider prophylactic medications are those who:
- Require abortive medications for migraine headaches more frequently than twice weekly.
- Have two or more migraine headaches a month that do not respond readily to abortive medications.
- Have migraine headaches that are interfering substantially with their quality of life and work.
- Cannot take abortive medications because of heart disease, stroke, or pregnancy, or cannot tolerate abortive medications because of side effects.
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