Pharmacological treatment of migraine: Drug classes, mechanisms of action, clinical trials and new treatments

Abstract

Migraine is the sixth most prevalent disease globally, a major cause of disability, and it imposes an enormous personal and socio‐economic burden. Migraine treatment is often limited by insufficient therapy response, leading to the need for individually adjusted treatment. In this review, we analyse historical and current pharmaceutical development approaches in acute and chronic migraine based on a comprehensive and systematic analysis of Food and Drug Administration (FDA)‐approved drugs and those under investigation. The development of migraine therapeutics has significantly intensified during the last 3 years, as shown by our analysis of the trends of drug development between 1970 and 2020. The spectrum of drug targets has expanded considerably, which has been accompanied by an increase in the number of specialised clinical trials. This review highlights the mechanistic implications of FDA‐approved and currently investigated drugs and discusses current and future therapeutic options based on identified drug classes of interest.

Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine

“…The involvement of glial cells in migraine has been addressed in several studies and hypotheses (e.g., [ 130 , 131 , 132 ]), but mainly in the context of the role of glial cells in cortical-spreading depression. The action of antagonists of and antibodies against CGRP and its receptor also affects glial cells expressing the CALCA gene, but the problem of epigenetic regulation of this gene as a target in migraine prevention and therapy is still a perspective [ 133 ].…”

Pharmacogenetics in Primary Headache Disorders

“…Genetic susceptibility factors differ between migraine with and without aura ( Pisanu et al, 2017a ). Other risk factors comprise concomitant psychological and psychiatric disorders ( Pisanu et al, 2020 ), hormonal status, myofascial syndromes, and the influence of various adverse environmental factors, including nutritional factors or stressful situations ( Chai et al, 2014 ; Pisanu et al, 2017b ; Marmura, 2018 ; Zobdeh et al, 2021 ). Numerous studies have identified a variety of factors that can trigger migraine attacks.…”

“…However, headache patients react differently to given drugs leading to a wide variety of treatment responses. It is estimated that only 50% of migraine patients adequately respond to acute and preventive therapy ( Pomes et al, 2019 ; Zobdeh et al, 2021 ). Likewise, many patients with cluster headache fail to respond adequately to pharmacological treatment approaches.…”

Prevention of Migraine

“…51 CGRP has been looked at as a potential target for migraine treatment as far back as the 1980s. 52 Early studies found levels of CGRP to be elevated during migraine when measured in external jugular blood. 53 CGRP levels normalized with treatment with the migraine-specific rescue medication, sumatriptan.…”