Memantine Prevents Radiation-Induced Cognitive Decline in Brain Metastases - A Randomized Placebo-Controlled Trial
In brief
Memantine raised cognitive scores by 11 points six months after brain radiation
In a randomized trial of 130 patients with brain metastases, those taking memantine scored 84 on a cognitive test six months after radiotherapy, compared with 73 for placebo recipients. Quality-of-life scores also improved, but appetite loss was more common with memantine, and the global cognitive benefit in the stereotactic radiosurgery subgroup remains uncertain.
- Journal
- International journal of radiation oncology, biology, physics (Q1)
- Published
- 25 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Haripriya Parapparambil Surendran, Debnarayan Dutta, Kalavagunta Sruthi, Mazhuvancherry Kesavan Unnikrishnan, Dhanya Chandran, Renjitha Bhaskaran, et al.
- PMID
- 42790603
- DOI
- 10.1016/j.ijrobp.2026.09.010
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (top studies of the week, 11 October 2026): Randomized memantine trial preventing RT‑induced cognitive decline
Abstract
BACKGROUND: This prospective, double-blind, placebo-controlled, randomized clinical trial evaluated the role of memantine in preventing cognitive decline following radiotherapy (RT) for brain metastases (BM). METHODS: Patients with BM undergoing either stereotactic radiosurgery (SRS) or whole-brain radiotherapy with or without hippocampal avoidance (HA/WBRT) were randomized to receive memantine (20 mg/day) or placebo for 6 months post-RT. Primary outcomes included cognitive function (Addenbrooke's Cognitive Examination [ACE]), quality of life (QoL; EORTC QLQ-C30 and BN20), white matter volume changes (MRI T2 FLAIR), plasma memantine levels (LC-MS/MS), and adverse events (CTCAE v5.0). RESULTS: 130 patients were enrolled (memantine n=66; placebo n=64; SRS n=75; HA/WBRT n=55). At 6 months post-RT, cognitive decline was significantly higher in the placebo group (mean ACE: 72.9 ± 20.2) than in the memantine group (83.9 ± 10.8; p=0.005). Memantine improved memory (p<0.001), delayed recall (p<0.001), and verbal fluency (p=0.007), with better domain-specific cognitive preservation in the SRS subgroup (p<0.001). Memantine was associated with improved cognitive function in both HA/WBRT and SRS cohorts; the effect was statistically significant in HA/WBRT patients, whereas in the SRS subgroup better domain-specific cognitive preservation was observed but the global cognitive effect estimate was underpowered. Global health status improved with memantine (median change +33.3 points) but was unchanged with placebo (between-arm difference +33.3 points, 95% CI +16.7 to +41.7; p<0.001). Common toxicities included appetite loss (25.7% vs. 12.5%) and gastric irritation (7.5% vs. 0%). White matter volume correlated negatively with cognitive decline (r = -0.544; p = 0.055). The optimal trough concentration (118.06 ng/mL) was achieved at 5 mg BID; while levels exceeded the alert threshold (300 ng/mL) at 10 mg BID for 6.25% patients. CONCLUSION: Memantine preserved cognitive function relative to placebo and improved QOL in patients receiving radiotherapy for BM, with benefits observed in both SRS and HA/WBRT cohorts.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.