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From the AAN and the American Headache Society: How to Choose Migraine Therapies: Pointers from a New Evidence Review

Rukovets, Olga

doi: 10.1097/

Although nearly 38 percent of migraineurs could benefit from preventative therapy, less than half of them currently use it, according to a 2007 study in Neurology. A new guideline on the treatment of migraines in adults, published in the April 24 issue of Neurology, asks: What are the effective pharmacologic and complementary medicine options for these individuals?

This guideline from the AAN Quality Standards Subcommittee and the American Headache Society is based on an analysis of studies conducted between 1999 and 2009; it updates a review released in 2000. Lead author Stephen D. Silberstein, MD, professor of neurology and director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia, PA, spoke with Neurology Today about what has changed in migraine care over the last decade, how he determines which therapies to use for individual patients, and where there is more need for research.

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There are several differences. We actually analyzed some of the information that was in the 2000 guideline because of new data available. For example, the antiepileptic drug (AED) topiramate — which is now approved by the FDA — had a minimal rating in the prior review since we didn't have the scientific evidence back then. Now, topiramate is rated as having strong evidence for its effectiveness [Level A]. The other change is, based on the scientific evidence, verapamil and gabapentin were both slightly downgraded from Level B to Level U, which means there isn't enough evidence to support or refute their effectiveness.

We also included a supplemental section on some of the over-the-counter and nonsteroidal anti-inflammatory drugs (NSAIDs), which is published as Part II of this guideline.

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The drugs with the highest evidence [Level A] include AEDs — topiramate, sodium valproate, and divalproex sodium, and some beta blockers [metoprolol, propranolol, and timolol]. This means that if you take any of those drugs, they've been shown to work through well-designed, placebo-controlled trials.

Additionally, for the short-term prevention of menstrually-associated migraines, we made recommendations for the use of triptans: frovatriptan (based on Level A evidence). We found that naratriptan and zolmitriptan were probably effective (based on Level B evidence).

Readers of this guideline should know, however, that there has not been enough clinical evidence to support the use of one migraine treatment over another.

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The evidence suggests that clomipramine is probably ineffective [based on Level B evidence] and that these therapies are possibly ineffective: acebutolol, clonazepam, nabumetone, oxcarbazepine, and telmisartan [based on Level C evidence]. That doesn't mean they won't work in everybody, but if you're trying to pick medications, you should at least start with medications that have the best evidence. Lamotrigine, for example, should not be used for migraine prevention [based on Level A evidence].

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Yes, in our review of other complementary treatments, we found that the herbal preparation butterbur was effective [based on Level A evidence]. Fenoprofen, ibuprofen, ketoprofen and naproxen (all NSAIDs), as well as magnesium, riboflavin, feverfew — which are all considered alternative therapies — were probably effective for migraine [based on Level B evidence]. Many of us use these in people who prefer not to use drugs at all, or in combination with drugs in order to enhance the benefit of traditional medication.

Possibly effective alternative care for migraines [Level C] included the NSAIDs — flurbiprofen and mefenamic acid, Co-Q10, estrogen, and the antihistamine cyproheptadine. We found inadequate data [Level U] to support or refute the use of aspirin, indomethacin, omega-3, or hyperbaric oxygen for acute migraine.

However, the clinical evidence for all of these treatments should be viewed carefully because we saw discrepancies in how patients were selected and how migraine severity was assessed in the related studies. The treatments are unregulated, and there were few or no studies detailing how to take these medications, particularly in conjunction with pharmacological options.

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It's always important to know more about the medications you are prescribing. Particularly, have they been shown to work? Just because there's no evidence for a drug doesn't mean it won't work, but it is and always has been good practice to know the evidence in order to make your own informed decisions.

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There's no way of knowing in advance who is going to respond to which medication, so in many ways it's trial and error. We often will look at the side effects of the medication. So, if somebody is overweight, topiramate is frequently associated with weight loss and we might pick that as the drug of choice for an overweight patient. As well, we might prescribe tricyclic antidepressants, which have been associated with weight gain, in a patient who needs to gain weight. We might also choose an antidepressant for a patient that has comorbid depression, and a beta-blocker for someone with hypertension or anxiety.

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I think one of the most significant things that we do not have are comparative drug trials. We don't know if a patient takes drug A or drug B which is better or which has less side effects. That's probably the major research question that we need to address. We also need long-term assessments of the safety and efficacy of migraine treatments, as well as studies on the optimal dosage of nonsteroidal and complementary migraine prevention treatments.

Importantly, I think we've proven here once and for all that many drugs work for the treatment of migraines, not all the drugs work, and that there are options.

Listen here as Dr. Stephen Silberstein discusses highlights of the new evidence-based review of migraine treatments:

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• Silberstein SD, Holland S, Ashman E, et al. Evidence-based guideline update: Pharmacologic Treatment for episodic migraine prevention in adults Part II. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012;78:1337-1345.
• Holland S, Silberstein SD, Ashman E, et al. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults Part I. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012;78:1346-1353.
• Lipton RB, Bigal ME, Stewart WF, et al, on behalf of the AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007; 68:343-349.
©2012 American Academy of Neurology