Antidepressant therapy in the management of glioblastoma multiforme: A systematic review and meta-analysis

To evaluate the association between antidepressant use and survival outcomes in patients with glioblastoma multiforme (GBM).

A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. MEDLINE, Embase, and LILACS were searched for observational studies evaluating the association between antidepressant use and survival in patients with GBM. Hazard ratios (HRs) for overall survival were pooled using a random-effects model. Subgroup analyses were performed by antidepressant class, timing of initiation, and patient age. Between-study heterogeneity was assessed using the I² statistic, and meta-regression was conducted to explore potential sources of variability.

Eight studies comprising 8915 patients were included. Antidepressant use was not significantly associated with overall survival (HR 1.09, 95% CI 0.76-1.55; p = 0.64), with substantial between-study heterogeneity (I² = 95%). Subgroup analyses revealed no significant survival association when stratified by antidepressant class (SSRIs alone: HR 0.95, 95% CI 0.73-1.25; SSRIs and TCAs combined: HR 1.18, 95% CI 0.62-2.26), timing of initiation (pre-diagnosis: HR 0.91, 95% CI 0.63-1.32; post-diagnosis: HR 1.28, 95% CI 0.64-2.54), or age. Leave-one-out sensitivity analysis confirmed the robustness of the null finding. Meta-regression did not identify antidepressant exposure as a significant source of heterogeneity. Gross total resection was consistently associated with improved survival across studies.

Current evidence does not support a survival benefit associated with antidepressant use in patients with GBM. Antidepressants should be prescribed based on psychiatric indications rather than with the expectation of oncological benefit. Prospective studies with standardized exposure definitions and molecular subtyping are needed to further clarify any potential therapeutic role.