Patient depressive symptoms and reciprocity are associated with distress in the caregiver of patients with migraine: insights from the MI-DEAR observational cohort study

As awareness of migraine disability is becoming higher, the recognition of the pivotal role of caregivers of people with migraine and their burden is still scarce. We aimed to investigate the factors associated with the distress of informal caregivers of patients affected by high-frequency or chronic migraine with depressive symptoms. All consecutive adult patients with high-frequency or chronic migraine and depressive symptoms were considered, along with their caregivers. Sociodemographic characteristics and the average weekly hours spent together were assessed among patients and their caregivers (dyads). In patients, we evaluated monthly migraine days (MMDs), monthly acute medications (MAMs), pain intensity, migraine-related disability, the composite 4D score on migraine burden, and depressive symptoms (Patient Health Questionnaire-9-PHQ-9). Caregivers filled in the Relative Stress Scale (RSS). The mutuality scale (MS) was also collected in the dyads. 154 dyads (308 participants) were enrolled (patients aged 42.6 years, SD 12.7; 80.5% female; and their caregivers aged 48.1 years, SD 12.2; 36.4% female). The mean shared reported time was 89.7, SD 29.7 h per week. In patients, PHQ-9 scores were higher in those with higher disability scores (MIDAS; p < 0.001), whereas MMDs were not directly related ( p = 0.356). The RSS score in caregivers was 20.6 (SD 10.9). Among caregivers’ features, the reciprocity subdomain of the MS was inversely related ( p = 0.009) to the perceived distress (RSS). The MS total scores and subdomains (p consistently < 0.05) were highly related within the dyad. A positive, mild relation was observed between caregiver RSS and patient PHQ-9 ( r = 0.197; p = 0.014) and 4D ( r = 0.234; p = 0.004) scores. Finally, when both caregiver and patient characteristics were included, the caregiver reciprocity MS subdomain ( p < 0.001) was the main factor associated with RSS scores. The MI-DEAR study highlighted the elevated perceived distress of caregivers of hard-to-treat patients with migraine and depressive symptoms. Low caregiver reciprocity, more severe patients’ depressive symptoms, and multidimensional migraine burden were associated with higher caregivers’ distress. The study was preregistered on clinicaltrials.gov, NCT07029126 on Jun 11th 2025.