Berger, MD, PhD, Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA. Winnick, MA, Soroka University Medical Center and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel; School of Optometry, University of California, Berkeley, Berkeley, CA. Popovsky, MS, Kaneb, BA, Berardino, BS, Georgetown University School of Medicine, Washington DC. Kaye, Pharm D, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA. Cornett, PhD, Department of Anesthesiology, Louisiana State University School of Medicine, Shreveport, LA. Kaye, MD, PhD, Departments of Anesthesiology and Pharmacology, Toxicology and Neurosciences, Louisiana State University School of Medicine, Shreveport, LA. Viswanath, MD, Department of Anesthesiology, Louisiana State University School of Medicine, Shreveport, LA; Valley Pain Consultants - Envision Physician Services, Phoenix, AZ; University of Arizona College of Medicine-Phoenix, Department of Anesthesiology, Phoenix, AZ; Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE. Urits, MD, Department of Anesthesiology, Louisiana State University School of Medicine, Shreveport, LA; Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston, MA.
Psychopharmacol Bull. 2020 Oct 15;50(4 Suppl 1):163-188.
Migraines are a common form of primary headache, affecting women more than men (17.4% and 5.7% of US population, respectively, a total of 12%) that carry significant morbidity and disability, as well as a hefty healthcare price tag. They are most prevalent in women of reproductive ages and are estimated to be the 6th disease in order of causing global burden. They are estimated to cause 45.1 million years lived with disability, or 2.9% of global years lost to disability. Migraine treatment divides into acute, abortive treatment for relief of an ongoing migraine attack, and prophylactic therapy to reduce the occurrence of migraines, specifically for patients suffering from chronic and frequent episodic migraines. Traditional abortive treatment usually begins with NSAID and non-specific analgesics that are effective in curbing mild to moderate attacks. 5HT-agonists, such as triptans, are often used for second-line and for severe attacks. Triptans are generally better tolerated in the longterm than NSAIDs and other analgesics, though they carry a significant side-effect profile and are contraindicated in large parts of the population. Prophylactic therapy is usually reserved for patients with frequent recurrence owing to medication side effects and overall poor adherence to the medication schedule. Importantly, medication overuse may actually lead to the development of chronic migraines from previously episodic attacks. Recent research has shed more light on the pathophysiology of migraine and the role of CGRP in the trigeminovascular system. Recent pharmacological advances were made in developing more specific drugs based on this knowledge, including CGRP neutralizing antibodies, receptor antagonists, and the development of ditans. These novel drugs are highly specific to peripheral and central 5-HT receptors and effective in the treatment of acute migraine attacks. Binding these receptors reduces the production of CGRP and Glutamate, two important ligands in the nociceptive stimulus involved with the generation and propagation of migraines. Several large clinical studies showed Lasmiditan to be effective in the treatment of acute migraine attacks. Importantly, due to its receptor specificity, it lacks the vasoconstriction that is associated with triptans and is thus safer is larger parts of the population, specifically in patients with cardiac and vascular disease. Though more research is required, specifically with aftermarket surveillance to elucidate rare potential side effects, Lasmiditan is a targeted anti-migraine drug that is both safe and effective, and carries an overall superior therapeutic profile to its predecessors. It joins the array of medications that target CGRP signaling, such as gepants and CGRP-antibodies, to establish a new line of care for this common disabling condition.
偏头痛是一种常见的原发性头痛,女性发病率高于男性(分别为 17.4%和 5.7%,共计 12%),其带来了显著的发病率和残疾率,以及高昂的医疗保健费用。它在育龄妇女中最为常见,据估计,它是按导致全球负担的顺序排列的第六种疾病。据估计,它导致 4510 万人丧失残疾生命年,占全球残疾损失年数的 2.9%。偏头痛的治疗分为急性和预防性治疗,前者用于缓解正在进行的偏头痛发作,后者用于减少偏头痛的发作,特别是对于患有慢性和频繁发作性偏头痛的患者。传统的急性治疗通常从 NSAID 和非特异性镇痛药开始,这些药物对轻度至中度发作有效。5-HT 激动剂,如曲坦类药物,通常用于二线治疗和严重发作。曲坦类药物在长期使用时通常比 NSAIDs 和其他镇痛药耐受性更好,尽管它们具有显著的副作用特征,并且在很大一部分人群中被禁忌。预防性治疗通常保留给因药物副作用和总体对药物治疗方案的依从性差而频繁复发的患者。重要的是,药物滥用实际上可能导致以前发作性偏头痛发展为慢性偏头痛。最近的研究更深入地了解了偏头痛的病理生理学以及 CGRP 在三叉神经血管系统中的作用。最近,基于这一知识,在开发更具特异性的药物方面取得了药理学进展,包括 CGRP 中和抗体、受体拮抗剂和 ditans 的开发。这些新型药物对周围和中枢 5-HT 受体具有高度特异性,对急性偏头痛发作有效。这些受体结合减少了 CGRP 和谷氨酸的产生,这两种重要的配体在涉及偏头痛发生和传播的伤害性刺激中起作用。几项大型临床研究表明,拉米地坦在治疗急性偏头痛发作方面有效。重要的是,由于其受体特异性,它缺乏与曲坦类药物相关的血管收缩作用,因此在更大的人群中更安全,特别是在患有心脏病和血管疾病的患者中。尽管需要进一步研究,特别是进行售后监测以阐明罕见的潜在副作用,但拉米地坦是一种安全有效的靶向偏头痛药物,与前几代药物相比具有整体更好的治疗效果。它加入了靶向 CGRP 信号的药物系列,如 gepants 和 CGRP 抗体,为这种常见的致残疾病建立了新的治疗线。