What Actually Causes Chronic Migraine? A Mechanistic Reading of Treatment-Resistant Migraine — Why CGRP antibodies work for some and not others

The CGRP antibody class blocks calcitonin gene-related peptide or its receptor. For patients whose migraine biology is dominantly driven through CGRP-dependent pathways, the response is excellent. For patients whose migraine has substantial contributions from non-CGRP pathways, the response is partial or absent. The CGRP antibody non-response, in this framework, is not necessarily failure of the medication. It is the readout of a case where the medication is operating downstream of a lesion that the medication does not address. Adding upstream work to CGRP antibody treatment often improves response substantially in cases where the antibody alone was insufficient.