A more optimistic outlook about disease-modifying therapies and depressive symptoms in multiple sclerosis: A cross-sectional analysis.

Disease-modifying therapies (DMTs) prevent relapses and slow disability progression in people with relapsing-remitting multiple sclerosis (pwRRMS). Yet, it remains unclear whether DMTs influence depressive symptoms. Prior research failed to account for antidepressant use. This study aimed to clarify whether DMT use is linked to decreased depressive symptoms in pwRRMS. This cross-sectional retrospective analysis included a consecutive sample of 782 pwRRMS assessed at a tertiary neuropsychiatry clinic between 2020 and 2025 in Toronto, Canada. Covariates included age, sex, education, Expanded Disability Status Scale scores, and disease duration. Stratified by the presence or absence of antidepressant use, analyses of covariance were undertaken to evaluate for a difference in Hospital Anxiety and Depression Scale depression sub-scale (HADS-D) scores between the presence or absence of DMT use, controlling for covariates (p < 0.050). Mean age was 41.9 years (SD = 10.51), 78.4% were female, median EDSS was 2.0 (IQR = 1.5-2.5), 80.3% received DMTs, and 38.3% used antidepressants. Only in the absence of antidepressants, DMT use was connected to reduced HADS-D scores (p = 0.011, η2 = 0.014), with a mean difference of -1.1 points (95% CI [-2.0, -0.3]). Overall, DMT use is independently associated with decreased depressive symptoms in pwRRMS not receiving antidepressants. This study supports the need to include measures of depressive symptoms in randomized controlled trials of DMTs.