Contributor: Jorge Chalit, OMS II Educational Pearls: Migraine pathophysiology Primarily mediated through the trigeminovascular system Serotonin, dopamine, and calcitonin gene-related peptide (CGRP) Trigeminovascular system is linked to the trigeminal nucleus caudalis, which relays pain to the hypothalamus and cerebral cortex One effective treatment for acute migraines is -triptan medications 5-HT1D/1B agonists such as sumatriptan Often combined with NSAIDs and dopamine antagonists (as antiemetics) in migraine cocktails Diphenhydramine (Benadryl) was shown to be ineffective in a randomized controlled trial comparing it with placebo and a dopamine antagonist antiemetic.  The -triptan medications carry significant risk for peripheral vasoconstriction and are therefore avoided in cardiovascular disease One serotonin agonist specifically approved for use in vascular disease Lasmiditan - 5-HT1F agonist Slightly different mechanism of action avoids peripheral vasoconstriction CGRP antagonists are also used in patients who are unresponsive to -triptans References 1. Friedman WB, Cabral L, Adewunmi V, et al. Diphenhydramine as adjuvant therapy for acute migraine. An ED-based randomized clinical trial. Ann Emerg Med. 2016;67(1):32-39.e3. doi:doi:10.1016/j.annemergmed.2015.07.495 2. Lasmiditan (Reyvow) and ubrogepant (Ubrelvy) for acute treatment of migraine. (2020). The Medical letter on drugs and therapeutics, 62(1593), 35–39. 3. Robbins MS. Diagnosis and Management of Headache: A Review. JAMA - J Am Med Assoc. 2021;325(18):1874-1885. doi:10.1001/jama.2021.1640 4. Vanderpluym JH, Halker Singh RB, Urtecho M, et al. Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis. JAMA - J Am Med Assoc. 2021;325(23):2357-2369. doi:10.1001/jama.2021.7939 Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit, OMSII