Effect of Atogepant on Sleep Quality and Sleep-Related Adverse Events in Adult Patients with Migraine: A Prospective...

Migraine is often associated with impaired sleep quality, including insomnia, fragmented sleep, and circadian rhythm disturbances. These factors can exacerbate migraine severity and chronification. Calcitonin gene-related peptide (CGRP), a key player in migraine pathophysiology, also influences sleep regulation. While CGRP monoclonal antibodies have shown mixed effects on sleep, no study to date has evaluated the impact of gepants on sleep quality. This study assessed whether atogepant, recently approved for migraine prevention, affects sleep quality and sleep-related adverse events in real-world settings.

We conducted a prospective, observational, open-label, single-center study. All received atogepant 60 mg/day up to 12 weeks. Adults (≥ 18 years) with migraine (with/without aura or chronic migraine) experiencing ≥ 4 monthly migraine days were enrolled. Inclusion required ≥ 1 month of headache diaries and stable preventive or sleep treatments for ≥ 3 months. Patients were accepted regardless of prior preventive failures. Exclusion criteria were unstable treatments, recent sleep-impacting disease, and pregnancy. Sleep quality was assessed using five validated questionnaires (Pittsburgh Sleep Quality Index [PSQI], Athens Insomnia Scale [AIS], Bergen, Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI]) at baseline and at follow-up. Migraine frequency, disability (Migraine Disability Assessment [MIDAS], Headache Impact Test [HIT-6]), allodynia (Allodynia Symptom Checklist [ASC-12]), acute medication use, and adverse events (AEs) were also recorded. Pre-post differences were assessed with Wilcoxon and McNemar's tests, while linear mixed-effects models were applied to evaluate the impact of clinical factors (response status, psychiatric comorbidities, prior anti-CGRP failures) on PSQI outcomes, with model fit estimated via REML and pseudo-R².

The study population included 43 participants (93.0% female, mean age of 51.6 [IQR 48.4-54.8] years, mean age at disease onset of 18.9 [16.0-21.7] years); 30 (69.8%) participants had chronic migraine, and among them, 23 (76.7%) had a concomitant diagnosis of medication overuse headache. Atogepant significantly improved sleep quality with PSQI scores decreased from 9.6 to 8.2 (p = 0.002) and improvements in AIS (p = 0.014) and Bergen scores (p = 0.046). Sleep duration was the only PSQI subdomain with a statistically significant change. No differences were found in ESS or ISI scores. Notably, no patients reported sleep-related AEs such as somnolence, nightmares, or vivid dreams. Psychiatric comorbidities were associated with poorer baseline sleep but did not influence the magnitude of improvement. Prior anti-CGRP failure predicted a lesser sleep benefit. Finally, migraine burden improved across all evaluated migraine-related variables. Only two patients discontinued treatment.

Atogepant improved subjective sleep quality without causing sleep-related adverse events, supporting its role in comprehensive migraine management, particularly in patients with disrupted sleep.