aprepitant and Migraine-Disorders

Substance P (SP)/Neurokinin 1 (NK1) receptor pathways have been repeatedly implicated in the pathophysiology of central, pulmonary, and gastric disorders. A large body of evidence that has been generated from animal experiments indicates that treatment with selective NK1 receptor antagonists might be effective in the treatment of certain forms of disorders, analgesia, depression, migraine, asthma, or gastrointestinal disorders. Accordingly, numerous NK1 receptor antagonists have either been synthesized and are under clinical development, or have already been tested in clinical trials. However, the initial encouraging clinical results were followed by repeated demonstration of a lack of effectiveness. Up to now, only one NK1 receptor antagonist, aprepitant, is available for therapeutical use. Aprepitant is a selective high-affinity human SP/NK1 receptor antagonist approved by the FDA in 2003. Aprepitant is indicated for prophylaxis of acute- and delayed-phase nausea and emesis caused by chemotherapy regimens. It is used in combination with a 5-hydroxytryptamine (5-HT3) antagonist and a corticosteroid. It is the first antiemetic agent that acts by binding the NK1 receptor. Research continues and novel molecules may show better pharmacokinetic and pharmacodynamic properties and, therefore, may achieve therapeutic success.

Topics: Analgesics; Antidepressive Agents; Antiemetics; Antineoplastic Agents; Aprepitant; Gastrointestinal Diseases; Humans; Migraine Disorders; Morpholines; Neurokinin-1 Receptor Antagonists; Neurotransmitter Agents; Receptors, Neurokinin-1; Respiratory Tract Diseases; Vomiting

To assess the efficacy and tolerability of oral aprepitant, a substance P/neurokinin A receptor antagonist, in controlling nausea associated with IV dihydroergotamine (DHE) administered for medically refractory migrainous headache in patients not responding to standard antiemetics or with a history of uncontrolled nausea with DHE.. This was a retrospective chart review of prospectively collected hourly diary data and clinical notes of patients hospitalized between 2011 and 2015 for inpatient treatment with DHE. Patients were classified using the International Classification of Headache Disorders, 3rd edition (beta version). Peak and average daily nausea scores from hourly diaries, or daily entries of notes, and concurrent antiemetic use were collected and tabulated.. Seventy-four patients, of whom 24 had daily diaries, with chronic migraine with or without aura, with or without medication overuse, or new daily persistent headache of a migrainous type, were identified. In 36 of 57 cases in which aprepitant was administered during hospitalization, there was a 50% reduction in the average daily number of as-needed antinausea medications. Of 57 patients, 52 reported that the addition of aprepitant improved nausea. Among 21 of 24 patients with hourly diary data, nausea scores were reduced and in all 12 with vomiting there was cessation of emesis after aprepitant was added. Aprepitant was well tolerated with no treatment emergent adverse events.. Aprepitant can be effective in the treatment of refractory DHE-induced nausea and emesis. Given the broader issue of troublesome nausea and vomiting in acute presentations of migraine, general neurologists may consider what place aprepitant has in the management of such patients.. This study provides Class IV evidence that for patients with medically refractory migraine receiving IV DHE, oral aprepitant reduces nausea.

Topics: Administration, Intravenous; Administration, Oral; Analgesics, Non-Narcotic; Antiemetics; Aprepitant; Dihydroergotamine; Humans; Inpatients; Migraine Disorders; Morpholines; Nausea; Prospective Studies; Retrospective Studies; Treatment Outcome