Beyond monotherapy: rational polytherapy in migraine

The past decade has seen significant advances in both the scientific and clinical understanding of migraine. At present, a considerable body of data indicates that migraine is characterized by at least three major pathophysiological features: dopaminergic hypersensitivity, inflammation, and relatively "low" 5-HT levels. Clinically, blocking dopamine receptors, reducing inflammation, and/or stimulating a subpopulation of 5-HT1 receptors are effective monotherapeutic approaches in many migraineurs. However monotherapeutic approaches to migraine do not provide rapid, consistent, and complete relief in all migraineurs. Therefore, if monotherapy is suboptimal, it follows logically that concurrent therapy (ie, polytherapy) aimed at modulating two or three of the biological systems should be more efficacious than modulating only a single system. The rationale for the combination use of dopamine antagonists, anti-inflammatory agents, and 5-HT1 agonists are described in the present report.