Side effects associated with current and prospective antimigraine pharmacotherapies

ABSTRACT

Introduction: Migraine is a neurovascular disorder. Current acute specific antimigraine pharmacotherapies target trigeminovascular 5-HT_1B/1D, 5-HT_1F and CGRP receptors but, unfortunately, they induce some cardiovascular and central side effects that lead to poor treatment adherence/compliance. Therefore, new antimigraine drugs are being explored.

Areas covered: This review considers the adverse (or potential) side effects produced by current and prospective antimigraine drugs, including medication overuse headache (MOH) produced by ergots and triptans, the side effects observed in clinical trials for the new gepants and CGRP antibodies, and a section discussing the potential effects resulting from disruption of the cardiovascular CGRPergic neurotransmission.

Expert opinion: The last decades have witnessed remarkable developments in antimigraine therapy, which includes acute (e.g. triptans) and prophylactic (e.g. β-adrenoceptor blockers) antimigraine drugs. Indeed, the triptans represent a considerable advance, but their side effects (including nausea, dizziness and coronary vasoconstriction) preclude some patients from using triptans. This has led to the development of the ditans (5-HT_1F receptor agonists), the gepants (CGRP receptor antagonists) and the monoclonal antibodies against CGRP or its receptor. The latter drugs represent a new hope in the antimigraine armamentarium, but as CGRP plays a role in cardiovascular homeostasis, the potential for adverse cardiovascular side effects remains latent.

KEYWORDS:

• Adverse side effects
• antimigraine drugs
• CGRP
• headache
• lasmiditan
• migraine
• serotonin(5-hydroxytryptamine
• 5-HT)
• triptans

Article highlights

• Migraine pathophysiology involves, amongst others, low plasma concentrations of serotonin (5-hydroxytryptamine; 5-HT) and high plasma concentrations of calcitonin gene-related peptide (CGRP).

• Consequently, the triptans (5-HT_1B/1D receptor agonists), the ditans (5-HT_1F receptor agonists), the gepants (CGRP receptor antagonists) and human(ized) monoclonal antibodies against CGRP or its receptor have been developed as antimigraine drugs.

• However, the above drugs are not completely free of adverse side effects.

• For acute antimigraine therapy, the triptans, ergots and non-steroidal anti-inflammatory drugs (NSAIDs) are effective, but may produce medication overuse headache (MOH) and a wide variety of adverse (mainly cardiovascular) side effects.

• Lasmiditan (a 5-HT_1F receptor agonist) is devoid of vasoconstrictor properties (unlike the triptans), but its capability to cross the blood brain barrier (BBB) results is central side effects (e.g. nausea, somnolence, fatigue, vomiting, paresthesia, dizziness, etc.).

• Regarding the CGRP receptor antagonists and humanized monoclonal antibodies against CGRP or its receptor, the further development of some of the former was interrupted because they produced hepatotoxicity; whereas the latter are promising and apparently devoid of important adverse side effects, but long term (Phase III and IV) studies are required to definitely delineate their adverse side effect potential.

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Declaration of interest

A MaassenVanDenBrink has received grants from Amgen, Novartis, Lilly and CoLucid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was partially supported by the following research grants: (i) Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT-UNAM-Mexico, grant No. IA203117 for Abimael González-Hernández); and (ii) Consejo Nacional de Ciencia y Tecnología (CONACyT-Mexico, Grant No. 219707 for Carlos M. Villalón)