Polytherapy in the preventive and acute treatment of migraine: fundamentals for changing the approach

The pathophysiology of migraine is complex and involves multiple neurophysiological pathways. Monotherapeutic approaches for migraine are the rule but many patients discontinue their medications owing to lack of efficacy. Polytherapy may provide a rational strategy for some of these individuals. Herein, we review the basis of polytherapy treatment for migraine. We suggest that refractory patients, with previous failure to single agents, may benefit from the use of a two- or three-drug regimen combining medications that target different neurotransmitter systems. In addition, those patients with high recurrence rates or not presenting pain free at 2 h and/or sustained pain free at 24 h may also respond better to combination therapy suited to their individual profile, which must include nonsteroidal anti-inflammatory agents plus a triptan or a gastrokinetic drug. The three-drug regimen may also be considered. Finally, changing the time medicine is taken (before the development of central sensitization and allodynia cutanea) and switching the choice of formulations to non-oral potentially achieves a better response and can be determined individually. Although highly speculative, these hypotheses could stimulate further controlled studies to support changing the current paradigm of monotherapeutic migraine treatment in some patients.