SSRIs Are Not Recommended as a Treatment for Glioblastoma
SSRIs should not be used as a therapeutic intervention for glioblastoma, as they have no established role in the treatment of this malignancy and recent high-quality evidence suggests potential harm. The standard of care for glioblastoma remains maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide 1.
Evidence Against SSRIs as Glioblastoma Treatment
Lack of Guideline Support
No major clinical practice guidelines recommend SSRIs for glioblastoma treatment. The EANO 2021 guidelines, ASCO-SNO 2022 guidelines, and ESMO guidelines comprehensively outline standard treatments (surgery, radiotherapy, temozolomide, bevacizumab, tumor-treating fields) but make no mention of SSRIs as therapeutic agents 1.
SSRIs are only mentioned in guidelines as adjuvant analgesics for pain management or as antidepressants for cancer-related fatigue, not as antitumor agents 1.
Recent High-Quality Evidence Shows Harm
The most recent and highest quality study (2024 Swedish registry-based cohort of 1,231 glioma patients) demonstrated that SSRI treatment was significantly associated with worse survival 2.
In grade 4 glioblastoma, SSRI treatment was associated with a hazard ratio of 3.32 (95% CI 2.69-4.10, P < .001) compared to patients without antidepressants, indicating substantially increased mortality risk 2.
In grade 2-3 gliomas, the hazard ratio for SSRI treatment was 3.26 (95% CI 2.19-4.85, P < .001) 2.
Conflicting and Inconclusive Earlier Studies
A 2020 Northwestern Medicine retrospective study of 497 GBM patients found no association between SSRI usage and overall survival 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 3.
A 2020 Swiss population-based study of 404 IDH-wildtype glioblastoma patients found no differences in overall survival between those who took antidepressants and those who did not (P = .356), confirmed in multivariate analysis (P = .315) 4.
An older 2011 Mayo Clinic retrospective review of 160 GBM patients suggested possible benefit (2-year survival 32% vs 17%, P = 0.18), but this was not statistically significant and predates the larger, more rigorous 2024 study 5.
Critical Clinical Interpretation
The weight of evidence, particularly the most recent and largest study, indicates SSRIs should be avoided as a treatment strategy for glioblastoma. While the 2024 Swedish study demonstrates association rather than causation, the magnitude of the negative association (HR >3) is clinically significant and concerning 2.
Appropriate Use of SSRIs in Glioblastoma Patients
SSRIs may be prescribed for their intended indication—treatment of depression—which is common in glioblastoma patients (27% prevalence) 2.
When treating depression in glioblastoma patients, clinicians should be aware of the potential negative survival association and consider this in shared decision-making 2.
SSRIs like paroxetine have been studied for cancer-related fatigue but showed no benefit over placebo in reducing fatigue in cancer patients 1.
Standard of Care Remains Unchanged
For patients <70 years with KPS >70: maximal safe resection followed by radiotherapy (60 Gy in 2 Gy fractions) with concurrent temozolomide (75 mg/m²/day) and six cycles of adjuvant temozolomide (150-200 mg/m²/day for 5 days every 28 days) 1.
MGMT promoter methylation status should guide treatment decisions in elderly patients, with temozolomide alone considered for methylated tumors and hypofractionated radiotherapy for unmethylated tumors 1.