Calcitonin Gene-Related Peptide (CGRP)-Targeted Treatments—New Therapeutic Technologies for Migraine

Migraine is ranked as the third most common disorder worldwide and is considered one of the most disabling neurological conditions. Its treatment has mostly relied on medications that were non-specifically developed for migraine, thus accompanied by low adherence, inadequate effectiveness and intolerable side effects. These recent years have seen the development of new migraine-specific therapies targeting the calcitonin gene-related peptide (CGRP) and its receptor. These newly developed therapies, the small molecule gepants targeting the CGRP receptor and the anti-CGRP monoclonal antibodies (mAbs), are currently available in the market and FDA-approved for migraine treatment. As they are migraine-specific therapies, they largely expand their use to patients that could not tolerate previous treatments, either for systemic contraindications or drug-to-drug interactions, or where any other available option was not efficacious. Randomized controlled trials have demonstrated the efficacy of these new medications, with minor adverse effects reported (most commonly nausea and constipation). This article will review the mechanism of action, indications, contraindications, and tolerability profile of gepants and anti-CGRP mAbs, by summarizing the available literature. Finally, avenues for future research will be identified, so that upcoming controlled studies may be designed to fill such gaps.