OBJECTIVES: Neurocognitive impairment affects about 50-90% of brain metastases patients who receive radiation therapy. However, literature search revealed that memantine had potential to prevent neurocognitive impairments induced by radiation therapy. However, due to lack of comprehensive data on memantine in prevention of neurocognitive impairments following radiation therapy, we conduct this systematic review to gather the safety and efficacy data of memantine therapy in prevention of neurocognitive dysfunction induced by radiation therapy in brain metastases patients.

METHODS: We performed a comprehensive literature search in PubMed^®, Embase®, Scopus^®, The Cochrane Library, ClinicalTrail.gov and Google scholar from inception until November 2021 to identify the full-text randomized clinical trials (RCTs) and non-randomized controlled studies that evaluated the impact of memantine in prevention neurocognitive dysfunction following radiation therapy among brain metastases patients.

RESULTS: A total of four eligible studies were selected in this review and that included 1444 [Intervention group (n=729) and control group (n=715)] patients with brain metastases who received radiation therapy for final analysis. Overall, in three studies (75%) found that the substantial improvement in neurocognitive function at least one or more parameter such as recall and recognition (P=0.39, P=0.10 and P=0.005), normal appearing white matter (P=0.01), verbal fluency (P=0.03 and P<0.001), and complex attention (P=0.01) and executive function (P=0.01) following memantine therapy compared to control group. Further, two studies (50%) reveal an improvement in patients’ quality of life following memantine therapy compared to the control group, but there was no significant difference in toxicity profile after memantine therapy compared to the control group in two studies.

CONCLUSIONS: This comprehensive review revealed that memantine therapy had considerable benefits in preventing neurocognitive dysfunction and enhancing patients’ quality of life following radiation therapy in brain metastatic patients. Hence, memantine therapy can be considered as a suitable option to prevent neurocognitive dysfunction during whole-brain radiation therapy.