Uncontrolled migraine symptoms substantially impair quality of life. Avoiding triggers, making lifestyle changes and employing abortive treatment can often control migraines. If these measures are unsuccessful, prophylactic treatment may be needed to prevent migraines. Parsekyan performed a review of articles and studies of prophylactic drugs and other measures used to prevent the onset of migraine headaches.

Prophylactic therapy may be indicated in patients with the following: (1) more than two headaches per month, (2) less frequent but more prolonged headaches (longer than two days) leading to substantial disability, (3) migraines that are refractory to abortive treatment measures, (4) inability to use therapies for acute attacks because of intolerability, contraindication or overuse (more than two per week), (5) migraines that are predictable in occurrence and (6) other migraine conditions, such as migraine with prolonged aura or hemiplegic migraine. Overuse of abortive therapy may result in rebound headaches. In these patients, the treatment drug should be withdrawn before preventive therapy is started.

Patients should keep a headache diary. The identification of migraine triggers may make prophylactic therapy unnecessary. Drug therapy may still be necessary to control symptoms. Prophylactics can be used daily on a continuous basis or scheduled according to predetermined triggers, such as the onset of menses. Women of childbearing age should be treated with prophylactics with caution because of the teratogenicity of most of the drugs used for this purpose. Because prophylactic therapy is rarely curative, patients must be aware of the potential need to continue to use abortive treatment. A 50 percent reduction in migraine incidence is considered successful prophylactic therapy.

The choice of prophylactic agent depends on patient considerations, the risk-benefit ratio, side effects and cost. Pharmacologic migraine prophylaxis should be initiated at a low dosage and titrated upward to optimize the benefit while avoiding side effects. Monotherapy should be used whenever possible. Prophylactic regimens should be used for a two- to three-month trial period to determine efficacy. Physicians should choose a drug that may benefit any comorbid condition the patient has. First-line agents with the greatest efficacy are beta blockers, tricyclic antidepressants and divalproex sodium (valproic acid). Beta blockers, most commonly propanolol hydrochloride, require one month of use before an effect can be noticed and do not reduce aura. Beta blockers with intrinsic sympathomimetic activity (such as pindolol) should be avoided in patients with migraine.

Tricyclic antidepressants often prevent migraine with a rapid response (within four weeks). Tertiary amines, such as amitriptyline hydrochloride, are the most effective formulation. Divalproex sodium can successfully prevent migraine headaches when taken in daily dosages of 250 to 1,500 mg. Second-line agents include calcium channel blockers and nonsteroidal anti-inflammatory agents. Naproxen sodium, taken in a dosage of 1,100 mg daily, is the most commonly used agent in this class.

Third-line agents reserved for use in severe or refractory cases are methysergide and phenelzine sulfate. Agents currently being studied for prophylactic use include fluoxetine, riboflavin and magnesium.

Nonpharmacologic measures to prevent migraine include avoidance of triggers such as environmental or hormonal factors, stress, sleep deprivation, medications such as oral contraceptives and hormone replacement therapy, and certain foods or drinks, including cheese, wine, alcohol, chocolate and caffeine. Alternative therapies with unsubstantiated efficacy include daily doses of feverfew, relaxation therapy, cognitive behavior therapy, acupuncture, massage and hot or cold packs.