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The diagnoses of glioblastoma multiforme (GBM) and depression are often found to coexist. The impact of selective serotonin reuptake inhibitors (SSRI) on treatment-related toxicity and outcome in patients with GBM is unclear.We retrospectively reviewed 160 patients with GBM who received treatment at our institution between 1999 and 2008. Those taking an SSRI during treatment for GBM were identified and toxicities were assessed.Median survival for the entire cohort was 1.05 years. A total of 35 patients (21.8%) took an SSRI during initial treatment for GBM. There was no statistical difference in the rate of ≥grade 3 toxicity in patients taking an SSRI when compared with those who were not (11.4% vs. 13.6%, respectively; P = 1.00). Two-year survival in the cohort of patients taking an SSRI was 32% versus 17% in those who were not (P = 0.18). After making adjustment for age, recursive partitioning analysis class, and extent of surgery, absence of an SSRI during treatment was associated with a hazard risk of 1.5 (95% confidence interval = 1.00–2.42; P = 0.05).This retrospective review suggests that concomitant use of an SSRI during treatment does not adversely affect survival. There was no increased toxicity with the use of SSRI concurrent with treatment of newly-diagnosed GBM.