Applied Evidence

Migraine: Expanding our Tx arsenal

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Beyond tried-and-true therapies are new therapeutic targets on the horizon—giving you a bigger toolbox to help patients abort and prevent migraine episodes.


› Offer treatment with a triptan to adult patients with moderate-to-severe episodic migraine. A

› Consider prescribing topiramate, divalproex sodium, metoprolol, propranolol, or the herbal, Petasites hybridum, for the prevention of recurrent episodic migraine that has not responded to a reduction in headache triggers. A

› Add onabotulinumtoxinA injection to your therapeutic toolbox as an effective preventive treatment for chronic migraine (≥15 headache days a month for 3 months). B

› Recommend magnesium and feverfew as adjunctive preventive treatments for migraine. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Migraine is a highly disabling primary headache disorder that affects more than 44 million Americans annually.1 The disorder causes pain, photophobia, phonophobia, and nausea that can last for hours, even days. Migraine headaches are 2 times more common in women than in men; although migraine is most common in people 30 to 39 years of age, all ages are affected.2,3 Frequency of migraine headache is variable; chronic migraineurs experience more than 15 headache days a month.

Migraine: Expanding our Tx arsenal ©Cath Riley/Science Source

Recent estimates indicate that the cost of acute and chronic migraine headaches reaches approximately $78 million a year in the United States. 4 This high burden of disease has made effective migraine treatment options absolutely essential. Recent advances in our understanding of migraine pathophysiology have led to new therapeutic targets; there are now many novel treatment approaches on the horizon.

In this article, we review the diagnosis and management of migraine in detail. Our emphasis is on evidence-based approaches to acute and prophylactic treatment, including tried-and-true options and newly emerging therapies.

Neuronal dysfunction and a genetic predisposition

Although migraine was once thought to be caused by abnormalities of vasodilation, current research suggests that the disorder has its origins in primary neuronal dysfunction. There appears to be a genetic predisposition toward widespread neuronal hyperexcitability in migraineurs.5 In addition, hypothalamic neurons are thought to initiate migraine by responding to changes in brain homeostasis. Increased parasympathetic tone might activate meningeal pain receptors or lower the threshold for transmitting pain signals from the thalamus to the cortex.6

Prodromal symptoms and aura appear to originate from multiple areas across the brain, including the hypothalamus, cortex, limbic system, and brainstem. This widespread brain involvement might explain why some headache sufferers concurrently experience a variety of symptoms, including fatigue, depression, muscle pain, and an abnormal sensitivity to light, sound, and smell.6,7

After taking the initial history (headache onset, location, duration, associated symptoms), focus attention on assessing the risk of intracranial pathology.

Although the exact mechanisms behind each of these symptoms have yet to be defined precisely, waves of neuronal depolarization—known as cortical spreading depression—are suspected to cause migraine aura.8-10 Cortical spreading depression activates the trigeminal pain pathway and leads to the release of pro-inflammatory markers such as calcitonin gene-related protein (CGRP).6 A better understanding of these complex signaling pathways has helped provide potential therapeutic targets for new migraine drugs.

Diagnosis: Close patient inquiry is most helpful

The International Headache Society (IHS) criteria for primary headache disorders serve as the basis for the diagnosis of migraine and its subtypes, which include migraine without aura and migraine with aura. Due to variability of presentation, migraine with aura is further subdivided into migraine with typical aura (with and without headache), migraine with brainstem aura, hemiplegic migraine, and retinal migraine.11

Continue to: How is migraine defined?


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