Depression and mobility-related disability in multiple sclerosis: a real-world cohort study

Abstract

Background: Patients with multiple sclerosis (MS) are at an increased risk of major depressive disorder (MDD), a known contributor to worse cognitive outcomes. Nevertheless, its influence on mobility-related disability in adults with MS remains unclear. Objective: To evaluate the impact of MDD on mobility-related disability in adult patients with MS. Methods: We conducted a retrospective real-world cohort study through the TriNetX Global Collaborative Network, including 67 healthcare organizations in the United States, from January 2010 to December 2023. Adult patients with MDD and ≥2 diagnostic records of MS were matched 1:1 with individuals with MS alone based on demographics and clinical characteristics using propensity score matching. Patients with motor-impairing neurological diseases or psychiatric comorbidities were excluded. Primary outcomes were gait or mobility abnormalities and falls. Secondary outcomes were initiation of physical therapy for functional rehabilitation and fractures associated with falls. Also, the use of high-efficacy disease-modifying drugs (DMDs) and systemic corticosteroids for relapse management was assessed. Results: After matching, 3,204 patients with MS and MDD and 3,204 controls with MS alone were included. Over 2 years, MDD was associated with a higher risk of gait or mobility abnormalities (19.0% vs 12.1%; RR, 1.57; OR, 1.70) and a higher hazard over time (HR, 1.53; 95% CI, 1.35-1.74). MDD was also associated with increased use of physical therapy (9.1% vs 6.7%; RR, 1.36; HR, 1.31; 95% CI, 1.09-1.56), high-efficacy DMDs (16.4% vs 11.3%; RR, 1.45; HR, 1.42; 95% CI, 1.24-1.62), and systemic corticosteroids (40.7% vs 32.2%; RR, 1.26; HR, 1.25; 95% CI, 1.15-1.35). Falls were slightly more frequent in the MDD group in risk analysis (6.1% vs 4.7%; RR, 1.29), but this difference was not significant in time-to-event analysis (HR, 1.21; 95% CI, 0.98-1.50). Fractures associated with falls were not significantly different between groups. Conclusion: In this real-world cohort, MDD in adults with MS was associated with a greater burden of mobility-related disability and rehabilitation use, with higher use of systemic corticosteroids and high-efficacy DMDs over 2 years. These findings highlight depression as an important clinical marker of worse functional prognosis in MS and support the importance of early psychiatric recognition and integrated multidisciplinary care.