Review/Advances in Neurological Therapeutics (2022). Functional disorders

Abstract

We reviewed advancements in the treatment of headache and epilepsy, primarily focusing on literature published in 2022.

CGRP (calcitonin gene–related peptide) agents like Galcanezumab, Eptinezumab, Fremamezumab, and Erenumab have shown promise for patients unresponsive to conventional treatments. The European Headache Foundation guidelines recommend CGRP antibodies as a first–line preventive treatment for migraine. Furthermore, emerging studies explore super–responders and non–responders to CGRP antibodies, indicating varying effectiveness and characteristic patient profiles. The text also highlights new acute migraine treatments, such as selective 5–HT1F receptor agonists (ditan drugs) and CGRP receptor antagonists (gepant drugs). Lasmiditan, a selective 5–HT1F agonist, avoids vasoconstriction side effects seen with triptans. Gepant drugs like zavegepant are redeveloped with improved safety profiles. Both classes of drugs hold potential for migraine treatment.

As for epilepsy, Deep brain stimulation (DBS) targeting the thalamus, especially the anterior nucleus, is explored for epilepsy management. DBS has gained FDA approval for drug–resistant focal seizures. The treatment showed a 75% seizure frequency reduction over seven years, and another observational study also showed a significantly decreased seizure frequency. DBS has shown efficacy not only for epilepsy but also for psychiatric conditions like depression. Additionally, levetiracetam was approved for status epilepticus in 2022. One Japanese study showed the non–inferiority of levetiracetam to phenytoin in convulsive status epilepticus. Fenfluramine hydrochloride for Dravet syndrome was also approved in the last year. Although its precise mechanism remains unclear, activation of the 5–HT receptor or modulation of the opioid receptor may be associated with seizure reduction.