The effect of antidepressants on glioblastoma survival: A systematic review and meta-analysis

Symptoms of depression are highly prevalent among patients with glioblastoma and have been associated with poor outcomes. In addition to managing depression symptoms, preclinical and clinical studies suggest that antidepressants may inhibit glioblastoma progression However, the effect of antidepressants on survival is unknown and results from existing studies are conflicting. We conducted a systematic review and meta-analysis to investigate the effect of antidepressant therapy on glioblastoma survival. We queried PubMed, Embase, Scopus, PsycINFO, and Web of Science from inception to March 2024 for studies investigating the overall survival of patients with glioblastoma treated with antidepressants. Results were combined using a restricted maximum-likelihood estimation random effects model. We identified 6 observational studies meeting inclusion criteria with 8,269 patients. Of these, 1,093 (13%) were treated with antidepressant therapy at some point after their glioblastoma diagnosis. Antidepressant therapy was not significantly associated with overall survival (HR 1.27, 95% CI 0.90-1.79, P = .17). In a subanalysis of studies that specified whether selective serotonin reuptake inhibitors were utilized, SSRI usage specifically was also not associated with overall survival (HR 1.08, 95% CI 0.58-2.03, P = .81). We observed considerable heterogeneity (I² = 92.7%, P < .001). Antidepressants were not significantly associated with overall survival in patients with glioblastoma. However, our meta-analysis was limited by significant heterogeneity observed across studies. The effect of antidepressants on outcomes in patients with glioblastoma remains uncertain. We observed conflicting results in the literature, with some studies suggesting decreased survival. Therefore, the role of antidepressants in patients with glioblastoma warrants further investigation.