Postoperative Gabapentinoid Use Is Associated with Improved Survival in Glioblastoma: A Nationwide Population-Based Study

Abstract Background Glioblastoma (GBM) is a highly aggressive primary brain tumor that can integrate into neural circuits implicated in tumor progression and treatment resistance. Gabapentinoids are proposed to disrupt such interactions. We analyzed postoperative gabapentinoid use and overall survival (OS) in nationwide adult GBM cohort. Methods This retrospective population-based study utilized the Turkish national healthcare registry, identifying adult patients with pathology-confirmed GBM who underwent surgery between 2016 and 2024. The primary endpoint was OS. Stabilized inverse probability of treatment weighting (sIPTW) was applied to adjust for potential confounders, and survival associations were evaluated using multivariable Cox proportional hazards models. Survival curves were analyzed using Kaplan–Meier estimator, and statistical significance was defined as two-sided p-value <0.05. Results Of 11,924 patients, 701 (5.9%) utilized postoperative gabapentinoids. In sIPTW-weighted analyses, gabapentinoid utilization was associated with reduced mortality risk (HR 0.75; 95% CI, 0.66-0.84; p < 0.001). Age-stratified analyses demonstrated effect modification, with survival benefit observed in patients aged ≥55 years (HR 0.70; 95% CI, 0.60-0.81) but not in those <55 years. Within older subgroup, both gabapentin (n = 349; HR 0.70; 95% CI, 0.59-0.83; p < 0.001) and pregabalin (n = 248; HR 0.68; 95% CI, 0.56-0.83; p < 0.001) independently improved OS. Dose-response analyses suggested lower-mortality exposure ranges (gabapentin: 1,200-2,400 mg/day; pregabalin: >400 mg/day). Conclusions In this nationwide cohort, postoperative gabapentinoid use was associated with improved survival in patients with GBM, particularly aged ≥55 years. These findings support targeting neuron-glioma axis and warrant prospective evaluation of gabapentinoids as adjuvant therapies in GBM.