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Levetiracetam may avert transformed migraines.

SAN FRANCISCO -- Levetiracetam is a promising drug for the prevention of attacks of transformed migraine, a notoriously tough-to-treat and common form of chronic daily headache, Dr. Alan M. Rapoport said at the annual meeting of the American Academy of Neurology.

His 3-month, prospective, open-label study in 36 patients with transformed migraine showed significant improvement by several measures with levetiracetam.

There is no Food and Drug Administration-approved therapy for prevention of transformed-migraine attacks. Triptans, which are a mainstay in the prevention of migraine, are typically ineffective in transformed migraine.

Levetiracetam (Keppra) is an antiepileptic agent currently approved only as add-on therapy for treatment of partial-onset seizures in adults. On the basis of favorable results in this hypothesis-generating study in patients with transformed migraine, however, the next step will be a larger, randomized, placebo-controlled clinical trial, said Dr. Rapoport, a neurologist at Columbia University in New York and codirector of the New England Center for Headache in Stamford, Conn.

Participants in the open-label levetiracetam study had previously failed on between one and three preventive drugs and had taken no more than one antiepileptic agent. They were placed on 250 mg/day of levetiracetam, with the dosage being bumped up by 250 mg/day every 5 days until reaching 1,000 mg once daily.

After the first month of therapy, the dosage could be further raised to a maximum of 3,000 mg daily in two divided doses.

Half of the patients encountered side effects, and 8 of 36 dropped out because of them. The most common were sleepiness, asthenia, and anxiety.

It has been estimated that transformed migraine affects 10 million Americans. Diagnostic criteria include headaches on at least 15 days per month, each lasting at least 4 hours, in individuals with a history of migraine earlier in life. The typical history is one of episodic migraine during the teens or 20s, with the headaches then gradually changing to become more frequent and less severe.

Transformed migraine tends to be more bilateral than episodic migraine and isn't usually associated with nausea, photophobia, or sensitivity to noise. Indeed, it often resembles chronic tension headache.

Despite the lesser severity of transformed-migraine headaches in comparison with episodic migraine, their high frequency results in substantially greater disability.

Why some migraineurs go on to transformed migraine and others don't remains unclear.

In a separate presentation at the meeting, Dr. Madeleine Kitaj reported that patients with transformed migraine display significantly greater sensitivity to mechanical and thermal pain during sensory testing than do migraine patients of similar age and years of headache. In her 81-patient, cross-sectional study, the most striking differences in pain sensitivity between the two groups were evident in the neck region rather than in the arm, jaw, or eye areas.

A longitudinal study would be required to establish whether patients destined to develop transformed migraine are in a state of chronic cervical hypersensitivity at baseline, before their migraine headaches begin to change. If that turns out to be the case, sensory testing of migraineurs might be useful in identifying patients at high risk for transformed migraine, observed Dr. Kitaj, a physician in private practice in Southbury, Conn.

Her study was funded by GlaxoSmithKline. She serves on the speakers' bureau for that and for other pharmaceutical companies.

Dr. Rapoport has served as a consultant for UCB Pharma Inc., which makes levetiracetam and sponsored Dr. Rapoport's study.


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Title Annotation:Clinical Rounds
Author:Jancin, Bruce
Publication:Internal Medicine News
Geographic Code:1USA
Date:Sep 1, 2004
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