Migraine is a common episodic pain disorder, the treatment of which can be acute to stop an attack or preventive to reduce the frequency, duration or severity of attacks. Preventive treatment is used when attacks are frequent or disabling. Many different medication groups are used for preventive treatment, including β-blockers, antidepressants and antiepileptic drugs. Their mechanisms of action include raising the threshold to migraine activation, enhancing antinociception, inhibiting cortical spreading depression, inhibiting peripheral and central sensitization, blocking neurogenic inflammation and modulating sympathetic, parasympathetic or 5-HT tone. In this article, I review evidence of the effectiveness of migraine preventive drugs. I also discuss the setting of treatment priorities.
Introduction
Migraine is a common episodic headache disorder that is characterized by attacks comprising various combinations of headache and neurological, gastrointestinal and autonomic symptoms. It has a one-year prevalence of ∼18% in women, 6% in men and 4% in children [1]. The International Headache Society (http://www.i-h-s.org/) subclassifies migraine into migraine without aura (1.1) and migraine with aura (1.2), the aura being the complex of focal neurological symptoms that most often precedes or accompanies an attack [2]. The pharmacological treatment of migraine can be acute (abortive) or preventive, and patients with frequent severe headaches often require both approaches. Preventive migraine treatment also includes nonpharmacological therapy, which is not discussed in this review. Preventive treatment is used to reduce the frequency, duration or severity of attacks. Additional benefits include improvement of responsiveness to acute attack treatment, improvement of function and reduction in disability. Preventive treatment might preclude the progression of episodic migraine to chronic migraine and result in reductions in the cost of health care [3]. In this article, I present background information about migraine physiology, followed by a discussion of the available preventive medications. This is divided into older generic drugs, newer, recently studied medications and other drugs for which there is limited evidence of efficacy or that are perceived as natural products.
Guidelines for the preventive treatment of migraine have been developed in the USA [4]. Indications include:
attacks that significantly interfere with a patient's daily routine, despite appropriate acute treatment;
failure of, contraindication to or troublesome adverse events (AEs) from acute medications;
acute medication overuse;
very frequent headaches (more than two per week);
patient preference;
special circumstances such as hemiplegic migraine or attacks with a risk of permanent neurological injury.
Prevention is not being used to the extent that it should be; only 5% of all migraineurs currently use preventive therapy to control their attacks [5].
Many medication groups are used for preventive migraine treatment (Table 1). The choice of preventive medication is empiric; it is influenced by efficacy, AEs and the patient's coexistent and comorbid conditions [1]. The chosen preventive agent should be started at a low dose and increased slowly until therapeutic effects develop or the ceiling dose is reached. A full therapeutic trial can take two to six months.
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