Survival Outcomes Associated with Antidepressant Use in Glioblastoma: A Cohort Study

Purpose Glioblastoma is the most common primary brain malignancy and carries significant mortality. Preclinical studies have highlighted the efficacy of antidepressant therapy in inhibiting glioblastoma progression; however, real-world evidence remains conflicting. We sought to investigate the impact of different commonly utilized antidepressant therapies on survival in patients with glioblastoma. Methods In total, 1464 consecutive patients with glioblastoma treated at a single institution from 2008 to 2023 were included for analysis. Multivariate cox regression analysis with antidepressant usage modeled as a time varying covariate was used to assess the effect of antidepressants while controlling for a priori selected clinical variables with known relevance to survival. Results The median age at diagnosis was 62 (IQR 52-70) years with a median overall survival of 13.8 months. Of the cohort, 44% utilized antidepressants after diagnosis, with SSRIs as the most common class utilized (26%). The median duration of any antidepressant therapy was 111 (IQR 9-303) days. In a time varying, multivariate cox regression, usage of SSRIs (HR 1.4, 95%CI 1.21-1.62), SNRIs (HR 1.33, 95%CI 1.03-1.72), serotonin modulators (HR 1.61, 95%CI 1.40-1.86), and atypical antidepressants (HR 1.7, 95%CI 1.28-2.26) were associated with worse survival. Amongst SSRIs, only escitalopram (HR 1.33, 95%CI 1.10-1.60) and citalopram (HR 1.31, 95%CI 1.01-1.70) were associated with worse survival. Conclusions SSRIs, SNRIs, serotonin modulators, and atypical antidepressants are associated with worse survival in patients with glioblastoma. Careful selection of antidepressant medication in patients with glioblastoma may be necessary to optimize outcomes.