Utilization of Selective Serotonin Reuptake Inhibitors Improves Survival in Glioblastoma: A Retrospective Study in a Large Cohort

Introduction: Glioblastoma is the most common primary brain malignancy and carries significant mortality. Though recent advances in therapy have improved outcomes, prognosis remains poor. Preclinical studies have highlighted the efficacy of antidepressant therapy in inhibiting glioblastoma progression. However, little data exists regarding the efficacy of antidepressants on glioblastoma survival. We sought to investigate the impact of antidepressant usage on survival in patients with GBM.

Methods: We retrospectively reviewed all adult GBM patients at a single institution from 2008 to 2023 who utilized antidepressant therapy after diagnosis. Log-rank tests and multivariate cox proportional hazards model was used to assess the effect of antidepressants on survival while controlling for known confounders.

Results: In total, 1341 patients met inclusion criteria. The average age at diagnosis was 62 years (IQR 52-70) with a median overall survival (mOS) of 14.5 months [95%CI 13.47 – 15.4]. Of the cohort, 441(33%) utilized SSRIs, 155(12%) serotonin modulators, 70(5.2%) utilized SNRIs, 38(2.8%) utilized atypical antidepressants, 23(1.7%) utilized tricyclics (TCAs), and 441(33%) did not utilize antidepressants after GBM diagnosis. Patients who utilized SSRIs had longer overall survival compared to those who were not on SSRIs (16.6 vs 13.1 months, p<.001). After multivariate cox proportional hazards analysis to adjust for known confounders, patients who used SSRIs had improved overall survival [adjusted Hazard Ratio (aHR) 0.76, 95%CI 0.67-0.87,p <.001]. Amongst the SSRIs, escitalopram (mOS 17.26 vs 13.71 months,p <.001) and citalopram (mOS 17.03 months vs 14.10, p=0.02) were associated with increased survival. Utilization of serotonin modulators, SNRIs, atypical antidepressants, and TCAs were not associated with a survival benefit.

Conclusion : In this single institution cohort, SSRI therapy was independently associated with improved survival in patients with GBM, while non-SSRI and tricyclic therapy were not. SSRI therapy may be associated with improved survival in patients with GBM. A definitive prospective study to answer this question is indicated.