NEW ORLEANS – Topiramate joins divalproex sodium, sodium valproate, metoprolol, propranolol, and timolol – plus the herbal supplement petasites, an extract of the butterbur plant – as a top choice for migraine prevention in newly updated guidelines from the American Academy of Neurology and the American Headache Society.
All are "effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity," the guidelines state.
Dr. Stephen Silberstein
"We didn’t have good evidence for topiramate" for the previous guidelines, published in 2000. "We do now," said lead author Dr. Stephen Silberstein, a professor of neurology at Jefferson Medical College in Philadelphia.
That evidence includes a study that found that 50 mg/day for 8 weeks reduced migraine frequency from a baseline of about six per month to about two, and decreased headache intensity and duration (Acta. Neurol. Scand. 2008;118:301-5).
Meanwhile, "we’ve downgraded verapamil and gabapentin because we didn’t have enough evidence" to maintain a strong recommendation, said Dr. Silberstein, who is also the director of the Jefferson Headache Center.
The guidelines were updated to incorporate newer studies, and include advice on about 40 drugs and 20 mostly over-the-counter (OTC) products, including NSAIDs, culled from the strongest of almost 300 studies. Frovatriptan was also found to be effective for preventing menstrual migraines.
"We used stricter criteria this time than we did the last time, and included a lot more details for over-the-counter [products] and nutraceuticals. We also provided the evidence for [why] certain drugs have proven not to be really effective, such as carbamazepine and lamotrigine," which appears to be "good for [migraine] aura, but not for the headache," Dr. Silberstein said in an interview.
Overall, the drug recommendations probably won’t surprise too many doctors, but will support "what they believe, and give them evidence for what they practice," he said.
However, "the fact that there’s such good evidence for butterbur" – the only OTC product listed as effective for migraine prevention, instead of "probably" or "possibly" effective – may be "new to doctors," he said.
One study found that 75 mg twice daily reduced migraine attack frequency by 48%, significantly better than placebo (Neurology 2004;63:2240-4).
"It’s a surprise to many physicians that some of the [nonpharmaceuticals] actually work," Dr. Silberstein said.
With so many drugs and OTC products in play, selection depends largely on side effect profiles and patient comorbidities.
Topiramate, for example, might make sense for obese patients because it helps with weight loss. It and valproate might also be wise choices for epileptics. Beta-blockers might be the way to go for patients with anxiety or essential tremors, but not if they have asthma.
Prophylaxis makes sense when people have one or more attacks a week; when acute medications fail or are used too much; and when migraines come with a prolonged aura or worrisome neurological symptoms, such as hemiparesis, Dr. Silberstein said.
Total health care costs go down when migraines are prevented, despite the upfront cost of the drugs, he noted (Headache 2003;43:171-8).
Dr. Silberstein is on the advisory panel of and receives honoraria from AGA, Allergan, Amgen, Capnia, Coherex, Colucid, Cydex, GlaxoSmithKline, Lilly, MAP, Medtronic, Merck, Minster, Neuralieve, NuPathe, Pfizer, St. Jude Medical, and Valeant. He is on the speakers bureau of and receives honoraria from Endo Pharmaceuticals, GlaxoSmithKline, and Merck. He serves as a consultant for and receives honoraria from Amgen and Novartis. His employer receives research support from AGA, Allergan, Boston Scientific, Capnia, Coherex, Endo Pharmaceuticals, GlaxoSmithKline, Lilly, MAP, Medtronic, Merck, the National Institute of Neurological Disorders and Stroke, NuPathe, St. Jude Medical, and Valeant Pharmaceuticals. Other authors also reported numerous financial relationships with companies that manufacture drugs used in migraine prevention.