Antiepileptic drug levetiracetam (Keppra) shown to help chronic daily headaches

Apr 27 2004

The antiepileptic drug levetiracetam (Keppra(R)) significantly reduced the frequency and impact of headaches in patients diagnosed with transformed migraine, according to a new study presented today at the 56th annual meeting of the American Academy of Neurology (AAN).

The study is one of the first to specifically evaluate a daily medication for the prevention of transformed migraine, one of the most common types of chronic daily headache and one that can have a major, negative impact on a person's ability to function and their quality of life.

"Transformed migraine is very challenging to treat, and there are currently no medications approved by the U.S. Food and Drug Administration for prevention of these headache attacks," said lead investigator Alan M. Rapoport, M.D., founder and co-director, The New England Center for Headache, Stamford, CT, and clinical professor of neurology at Columbia University College of Physicians & Surgeons, New York. "Our findings suggest that levetiracetam is a promising drug for the treatment of transformed migraine," he said. Levetiracetam is currently approved by the F.D.A. for the adjunctive treatment of partial-onset seizures in adults.

The study showed that three months of treatment with levetiracetam significantly improved various headache measures compared to baseline. It reduced:

• Headache frequency by 35 percent, from 24.9 days of headache/month to 16.2 days of headache/month (p < 0.001)
• The average number of moderate or severe days of headache by 42 percent, from 16.8 days/month to 9.7 days/month (p < 0.01)
• MIDAS (Migraine Disability Assessment) scores by 35 percent, from 62.8 to 40.8 (p < 0.01); and HIT (Headache Impact Test) scores by six percent, from 63.4 to 59.4 (p < 0.01).

MIDAS and HIT are standard measures of how much disability is caused by headaches over a three-month period. "Our findings are encouraging not only because levetiracetam helped many of our patients, but also because most of them had previously failed on standard migraine preventive therapies," said co-investigator Marcelo Bigal, M.D., Ph.D., director of research, The New England Center for Headache, and associate professor, Department of Neurology, Albert Einstein College of Medicine, Bronx, NY. "The next step is to see if the findings can be replicated in a larger, randomized, placebo-controlled trial." The prospective, open-label study included 36 transformed migraine patients (26 women and 10 men), averaging 46.5 years old.

All the participants had previously failed on one, but not more than three preventive drugs, and had taken no more than one antiepileptic drug. After a baseline period, participants received levetiracetam 250 mg/day, and increased it by 250 mg every fifth day up to a dose of 1000 mg/day.

After the first month, doses could be further increased to 3000 mg/day. At baseline and monthly intervals during the three-month study, the investigators assessed headache frequency, the number of days with moderate or severe headaches, and MIDAS and HIT scores. No serious adverse events were reported. Half of the participants reported side effects, with eight (22.2 percent) dropping out of the study because of them. The most common side effects were somnolence (27.7 percent), asthenia (27.7 percent), and anxiety (13.8 percent).