DHE - past, present, and future: a narrative review.

Dihydroergotamine (DHE) was first approved in 1946 for the acute treatment of migraine. Its efficacy when administered as an intravenous (IV) injection explains its enduring use in the management of migraine today. More recently, attention has been focused on the development of formulations delivered by the inhalational route to either the nasal mucosa or lung with the objective of providing a product that enables easy, needle-free, "at-home" use that is rapidly effective. Three new DHE products for migraine (two administered by nasal delivery) have been Food and Drug Administration (FDA) approved in the past five years with two others using pulmonary delivery in clinical development attempting to optimize outcomes for subjects requiring "at-home" migraine treatment. This narrative review describes those DHE development programs, and others that have failed, with the objective of providing a broad perspective on various approaches, including those that may be more likely to achieve the goals of high efficacy rates, rapid relief, and convenience of use. In addition, DHE has been investigated for potential repurposing of other indications. These too are described.