Abstract
Glioblastoma (GBM) is the most common and aggressive form of malignant glioma in adults with a median overall survival (OS) time of 16–18 months and a median age of diagnosis at 64 years old. Recent work has suggested that depression and psychosocial distress are associated with worse outcomes in patients with GBM. We therefore hypothesized that the targeted neutralization of psychosocial distress with selective serotonin reuptake inhibitor (SSRI) antidepressant treatment would be associated with a longer OS among patients with GBM. To address this hypothesis, we retrospectively studied the association between adjuvant SSRI usage and OS in GBM patients treated by Northwestern Medicine-affiliated providers. The medical records of 497 GBM patients were analyzed after extraction from the Northwestern Medicine Enterprise Data Warehouse. Data were retrospectively studied using a multivariable Cox model with SSRI use defined as a time-dependent variable for estimating the association with OS. Of the 497 patients, 315 individuals died, while 182 were censored due to the loss of follow-up or were alive at the end of our study. Of the 497 patients, 151 had a recorded use of SSRI treatment during the disease course. Unexpectedly, SSRI usage was not associated with an OS effect in both naïve (HR = 0.81, 95% CI = 0.64–1.03) and adjusted time-dependent (HR = 1.26, 95% CI = 0.97–1.63) Cox models. Ultimately, we failed to find an association between SSRI treatment and an improved OS of patients with GBM. Additional work is necessary for understanding the potential therapeutic effects of SSRIs when combined with other treatment approaches, and immunotherapies in particular, for subjects with GBM.
Highlights
Glioblastoma (GBM) is the most common form of malignant glioma, with a median overall survival (OS) time of 16–18 months in adults (Koshy et al, 2012; Stupp et al, 2017)
Using a time-dependent Cox model, we discovered that patients with GBM treated with selective serotonin reuptake inhibitor (SSRI) did not have an associated improvement of OS as compared to untreated GBM patients
This finding differs from our original hypothesis, as well as the implications of the previous study by Caudill et al (2011), which indicated a potential increase in OS among GBM patients that had used SSRIs
Summary
Glioblastoma (GBM) is the most common form of malignant glioma, with a median overall survival (OS) time of 16–18 months in adults (Koshy et al, 2012; Stupp et al, 2017). Patients with GBM are poorly responsive to conventional therapy, which includes maximal surgical resection when possible combined with radiation treatment, chemotherapy with the DNA-alkylating drug temozolomide, and more recently, tumor treating fields. Due to the persistently grim prognosis associated with GBM, experimental approaches evaluating diverse immunotherapeutic treatments including vaccines, immune checkpoint inhibitors, and CAR T-cells are actively under clinical study. To-date, these methods have failed to demonstrate improvement in GBM patient OS among phase III clinical trials (Weller et al, 2017; Reardon et al, 2017; Schuster et al, 2015; Bloch et al, 2017), motivating research into adjunct treatments that may improve survival through a synergistic mechanism (Ladomersky et al, 2018; Tan et al, 2018).
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