Refractory migraine profile in CGRP-monoclonal antibodies scenario

Objective: Refractory migraine (Ref-M) represents a conundrum that headache experts have to face with. We aim to investigate whether a peculiar profile may characterize patients with Ref-M according to 2020 European Headache Federation criteria. Furthermore, to substantiate a dysfunctional dopaminergic pathway involvement in these patients, we explored the effectiveness of olanzapine. Materials & Methods: Eighty-four patients (fitting previous Ref-M criteria of the 2014) were treated with erenumab for six months. Differences between clinical and demographic features of responder (Ref-M according to 2014 criteria) and not-responder (Ref-M according to 2020 criteria) patients to CGRP-mAbs were investigated and their predictive values assessed. In fifteen patients with Ref-M not responders to CGRP-mAbs, olanzapine was administered (5 mg/die) for 3 months and frequency and pain intensity of migraine attacks were estimated. Results: Patients with Ref-M not responsive to CGRP-mAbs (29/84) when compared with Ref-M responsive to CGRP-mAbs showed higher baseline frequency of migraine attacks, medication overuse and pain catastrophizing scale (PCS) scores. Logistic regression analyses showed that frequency of attacks, medication overuse and PCS score represent independent negative predictors of CGRP-mAbs response. A ≥50% reduction of headache days/month was observed after olanzapine treatment in 67% of patients with Ref-M not responsive to CGRP-mAbs. Conclusions: We outline that higher frequency of migraine attacks, medication overuse and pain catastrophizing characterize patients with Ref-M not responsive to CGRP-mAbs. In this frame, olanzapine effectiveness on frequency and pain intensity of migraine attacks supports the hypothesis that migraine refractoriness may be subtended by a prominent involvement of the dopaminergic pathway.