Frequency, disability must guide migraine prophylaxis.

SCOTTSDALE, ARIZ. -- Monitor patients' headache frequency and disability to guide the pharamacologic prevention of migraine, Dr. Stewart J. Tepper said at a symposium sponsored by the American Headache Society.

"The goal should be to decrease migraine frequency by half and decrease duration and intensity, and comorbid illnesses are the critical aspect in picking the correct drug," said Dr. Tepper, director of the New England Center for Headache, New Haven, Conn.

Disability is as important in daily pharmacologic prevention as it is in acute treatment, and is the key to assessing therapeutic need, said Dr. Tepper, who is also with Yale University.

Circumstances that might warrant preventive treatment include:

* Frequent or infrequent migraine that significantly interferes with the patient's daily routine despite acute treatment.

* Failure of, contraindication to, or troublesome side effects from acute medications.

* Special circumstances, including hemiplegic migraine and attacks with a risk of permanent neurologic injury.

* Pattern of increasing attacks over time, with the risk of developing rebound headache with medicines for acute attack.

* Patient preference (the desire to have as few acute attacks as possible).

* Pregnancy with severe, disabling attacks accompanied by nausea, vomiting, and possibly dehydration.

Before choosing your approach, ask about family clinical response to specific medications. "If you have family members with success using propranolol, that's helpful because they're chips off the old block genetically," Dr. Tepper said.

He also emphasized the importance of using the lowest dose possible of a long-acting formulation and giving each treatment an adequate trial.

"It's critically important that you look for a pharmacologic twofer.... You want to treat comorbid illnesses while avoiding contraindicated medications," he said. "And the patient diary is a must if you want to make sure your outcomes are met."

The U.S. Headache Consortium guidelines, now in the process of revision, classify preventive migraine medications on the strength of scientific evidence from randomized, controlled trials in descending order from most evidence to least (A, B, or C) and by groups of effectiveness, 1 being most efficacious and 3 the least.

In group 1, class A drugs include the antiepilepsy drugs divalproex sodium and topiramate. Both drugs are associated with significant side effects, and divalproex use is limited by its propensity to cause birth defects and polycystic ovaries.

"We should not be using divalproex as first-line therapy in women of childbearing age," Dr. Tepper said, adding that patients offered topiramate should be warned about the risk of paresthesias and of reversible angle-closure glaucoma. "When patients develop paresthesias, I find that potassium supplementation is helpful."

The group 2 antiepilepsy drug gabapentin is class B but has not received Food and Drug Administration approval for migraine prevention. All three medications in this class produced modest reductions in migraine attacks in clinical trials. Gabapentin, which produced its best results at a dose of 2,400 mg, had a high dropout rate due to dizziness and drowsiness, he said.

Included on the consortium's group 1 list are five alternative medications, of which three--chelated magnesium, riboflavin, and feverfew--are listed as class B. However, feverfew may be dropped from class B in the revision because of bad showings in two randomized, controlled trials.

The revision is also expected to include butterbur root and coenzyme Q10 in class B, Dr. Tepper noted.

Tricyclic antidepressants are clearly the standard when there are such comorbid illnesses as insomnia, neck pain, and depression, he said.

"Amitriptyline is a class A drug in group 1 but is not FDA approved for this indication. The other tricyclics are all class C in the guidelines, but since the guidelines were released there have been two small randomized, controlled trials of venlafaxine showing effectiveness in episodic migraine at a dose of 150 mg."

Dr. Tepper predicts that selective serotonin reuptake inhibitors, currently listed as class B and C medications, will be demoted in the revised guidelines.

"And I don't list botulinum neurotoxin type A because the evidence has shown ineffectiveness in episodic migraine, and studies are pending in chronic migraine," he added.

Two [beta]-blockers, which Dr. Tepper prescribes for comorbid anxiety and hypertension, have been approved for episodic migraine prevention: Propranolol and timolol both have class A evidence and lie in group 1.

All of the calcium channel blocking agents available in the United States have class B scientific evidence. Calcium channel blockers are the drugs of choice for hemiplegic migraine and basilar-type migraine, Dr. Tepper explained.

Dr. Tepper disclosed significant relationships with Valeant Pharmaceuticals, Pfizer, Alexa, AstraZeneca, Endo Pharmaceuticals, and Eisai as the recipient of research grants; with Allergan Inc. as a consultant, lecturer, and recipient of research grants; with Johnson and Johnson as a lecturer and recipient of research grants; and with Merck U.S. Human Health as a consultant and recipient of research grants.

BY BRUCE K. DIXON

Chicago Bureau