Headache Frequency and Depressive Symptoms Are Independently Associated With Disability in Migraine: A Large-Scale,...

The burden of migraine is influenced by a complex interplay of headache characteristics, psychiatric comorbidities, and sleep disturbances. This study aimed to examine factors independently associated with migraine-related disability and severe functional impairment in a large clinical cohort.

This cross-sectional study included 1186 patients diagnosed with migraine according to ICHD-3 criteria. We collected data on demographics, headache characteristics (monthly headache days [MHD] and intensity [VAS]), and potential medication overuse (pMOH). Disease burden was assessed using the Migraine Disability Assessment (MIDAS) score. Psychiatric comorbidities and sleep quality were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI). Multiple linear and binary logistic regression analyses were performed. Candidate variables were selected a priori based on clinical relevance and data availability. Multicollinearity diagnostics, sensitivity analyses using available medication-related variables, and model performance assessments were also conducted.

The cohort had a mean age of 39.5 ± 12.1 years, with a high prevalence of moderate-to-severe disability (64.7%), anxiety symptoms (52.4%), and poor sleep (48.2%). In the multiple linear regression model (adjusted R² = 0.518, p < 0.001), MHD (β = 0.581, p < 0.001) and PHQ-9 score (β = 0.152, p < 0.001) showed the strongest independent associations with the MIDAS score. Headache intensity (VAS) was also significant but had a smaller effect size (β = 0.055, p = 0.031). GAD-7 and PSQI were not independently associated with MIDAS after full adjustment. Sensitivity analyses additionally adjusting for available medication-related variables yielded similar results. The logistic regression model showed acceptable discrimination (AUC = 0.86, 95% CI: 0.83-0.89) and calibration (Hosmer-Lemeshow χ² = 7.42, p = 0.492).

In this cross-sectional cohort of patients with migraine, headache frequency and depressive symptoms were the factors most robustly associated with migraine-related disability among the available variables. The associations of anxiety symptoms and poor sleep with disability were attenuated after adjustment for headache frequency and depressive symptoms, which may reflect shared variance rather than a confirmed mediation pathway. These findings support routine assessment of headache frequency and depressive symptoms in migraine care, while longitudinal studies with detailed medication and psychosocial data are needed to clarify temporal and causal relationships.