Influence of Antidepressants on the Relationship Between Disease Duration and Depressive Symptoms in Multiple Sclerosis

OBJECTIVE: Studies have not shown an association between multiple sclerosis (MS) disease duration and depression among people with MS. However, whether antidepressant use influences this possible relationship remains unknown. The authors evaluated whether antidepressant use moderates the association between disease duration and clinically significant depressive symptoms among individuals with MS. METHODS: A consecutive sample of 1,076 adults with MS received psychometric testing during clinical care at a tertiary neuropsychiatry clinic in Toronto from 2020 to 2025. Demographic and disease-related data were gathered via retrospective chart review. A logistic regression analysis adjusted for age, sex, education, Expanded Disability Status Scale (EDSS) scores, and Symbol Digit Modalities Test scores was undertaken to evaluate whether the interaction between antidepressant use and disease duration predicted clinically significant depression (Hospital Anxiety and Depression Scale depression subscale score ≥8). Stratified by antidepressant use, secondary regression analyses controlling for the same covariates were used to evaluate whether disease duration was independently associated with depression. Statistical significance was set at p<0.05. RESULTS: Mean participant age was 43.9±11.5 years, 76% were women, the mean length of education was 16.0±3.1 years, and the median EDSS score was 2.0 (interquartile range 1.5-3.5). Antidepressant use significantly moderated the relationship between disease duration and clinically significant depressive symptoms (p=0.017). In the absence of antidepressants, increased disease duration predicted elevated odds of depression (OR=1.02, p=0.038) but not in the presence of antidepressants (OR=0.98). CONCLUSIONS: Antidepressant use is associated with a lessened influence of prolonged disease duration on an increased odds of clinically significant depression among people with MS.