Effect of long‐term treatment with memantine on mortality in patients with major cognitive disorders: A systematic review and meta‐analysis

BACKGROUND Dementia is responsible for a reduction in life expectancy, and the effect of memantine on mortality is still poorly understood. Our aim was to evaluate the effect of long‐term treatment with memantine on all‐cause mortality. METHODS In this systematic review and meta‐analysis, we searched five databases from their creation to June 2024. RESULTS We found 12 randomized trials ( n = 4266) and 7 observational studies ( n = 20,216). Treatment with memantine was associated with a reduction in all‐cause mortality (risk ratios [RRs] 0.81, 95% CI: 0.72–0.92, p = 0.001). In the sensitivity analysis, the pooled RR was similar for randomized controlled trials (RCT) (RR 0.86) and non‐randomized studies (RR 0.81) but pooled results from RCTs did not reach statistical significance (95% confidence interval [CI]: 0.59–1.26, p = 0.45), while they did for observational studies (95% CI: 0.70–0.95, p = 0.008), so we consider the overall evidence as of low certainty. CONCLUSION Our results suggest that the use of memantine in patients with dementia may be associated with a reduction in all‐cause mortality. Highlights Dementia reduces patients’ survival and the effect of long‐term use of memantine on all‐cause mortality is not well known. This systematic review and metanalysis included 19 studies including more than 24000 patients. We found that memantine in patients with dementia may be associated with a reduction in all‐cause mortality.