Shafqat R, Flores-Montanez Y, Delbono V, et al. - In this study, researchers sought to discuss the coming of age of dihydroergotamine (DHE; one of the first synthesized migraine-specific treatments) through its prototype, its pharmacology, and its pharmacokinetics, and more importantly, the special considerations – who should use it, under what circumstances, and when to use with caution. Although DHE is an older drug with an interesting history, it is still clinically useful for cases with migraine attacks not responsive to triptans, who have a greater burden from migraine, and in refractory migraine. DHE demonstrates greater alpha-adrenergic antagonist activity, lower arterial vasoconstriction, less dopaminergic agonism, and lower emetic potential, when compared with ergotamine. At present, its administration is done as a liquid nasal spray or by injection, though oral formulations have been utilized historically, and development of an intranasal powder is underway. Pregnant women should not be administered DHE and other ergot alkaloids as they reduce uterine blood flow and enhance uterine muscle contractility predisposing to spontaneous abortion. Further, DHE is contradicted during lactation as it can result in gastrointestinal distress and weakness in infants; it can also suppress milk production. In patients with cardiovascular risk factors, DHE should be administered with caution. DHE can be administered at home, in the clinic, and in the hospital with good outcomes in select patients. They suggest all providers who care for patients with migraine to be aware of its properties and precautions.