Migraine and treatment-resistant depression.

Migraine and major depressive disorders (MDD) or treatment resistant depression (TRD) represent a significant global burden and are often comorbid, further complicating diagnosis and treatment. Epidemiological studies have demonstrated a bidirectional relationship between migraine and MDD/TRD, with patients suffering from one disorder exhibiting a heightened risk of developing the other. This association is believed to result from shared genetic factors, neurotransmitter dysregulation, inflammation, hormonal alteration, and other conditions comorbid with both disorders. Emerging evidence suggests that therapeutics targeting common pathways in both disorders may be beneficial for comorbid patients. Novel therapeutics for migraine or MDD/TRD, such as calcitonin gene-related peptide (CGRP)-targeting therapy, onabotulinumtoxinA, ketamine/esketamine, vagus nerve stimulation or transcranial magnetic stimulation, may be helpful in selected patients with comorbid migraine-MDD/TRD. Nevertheless, continued efforts are needed to improve early detection and intervention, to better understand the complex interplay between genetic, environmental, and psychosocial factors contributing to this comorbidity, to identify novel therapeutic targets, and ultimately, to alleviate the disease burden caused by this comorbidity.