Neurophysiological Effects of Atogepant in High-Frequency Episodic Migraine (ATOM project)

This is a prospective, open-label study. A comprehensive neurophysiological assessment was performed at baseline (T0) and after a 3-month atogepant 60 mg QD treatment (T1) to investigate whether clinical response to treatment was associated with changes in neurophysiological signatures in individuals with HFEM. Subjects between 18 and 70 years of age were consecutively screened and enrolled among those attending the outpatient clinic of the Headache Science & Neurorehabilitation Unit of the IRCCS Mondino Foundation of Pavia (Italy) in the period between April 2024 to February 2025. At T0, we collected clinical and demographic features, and we revised paper headache diaries to collect monthly migraine days (MMDs) and days and doses of monthly drug intake. All subjects completed validated questionnaires used to evaluate migraine-related disability (Migraine Disability Assessment Scale – MIDAS; Headache Impact Test 6 – HIT-6), allodynia (Allodynia Symptom Checklist 12 – ASC-12), psychological symptoms (Beck Depression Inventory – BDI; State-Trait Anxiety Inventory – STAI); Patient Health Questionnaire-9 – PHQ-9; Perceived Stress Scale – PSS) and level of physical activity (International Physical Activity Questionnaire – IPAQ). At T0, all participants underwent a comprehensive neurophysiological assessment between 09:00 and 12:00. Subjects were tested in the interictal migraine phase, defined as having no headache and not having taken any acute antimigraine drugs in the 48 hours prior to assessment. In case a participant was not in the interictal migraine phase, all assessments were rescheduled to follow study procedures. The possible onset of headache and associated symptoms in the 12 hours after the test were also recorded in the headache diary. Neurophysiological assessment At T0 and T1, subjects underwent the following neurophysiological assessments: i) nociceptive Withdrawal Reflex (nWR); ii) habituation of nociceptive blink reflex (nBR); iii) habituation of visual Evoked Potentials (VEPs). The nWR and nBR assessments were performed according to the established protocols previously used by our group, whereas VEPs were conducted following the methodology described by Ambrosini et al.