Traumatic brain injury (TBI) affects millions of people around the world and amongst other effects, causes cognitive decline, neurodegenerative disease and increased risk of seizures and sensory disturbances. Excitotoxicity and apoptosis occur after TBI and are mediated through the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Memantine is effective in blocking excessive activity of NMDA-type glutamate receptors and reduces the progression of dementia and may have benefits after TBI. Here, we performed a systematic review of the literature to evaluate whether memantine is effective in improving outcomes, including cognitive function in patients with TBI. Our search yielded only 4 randomized control trials (RCTs) that compared the effects of memantine to placebos, standard treatment protocols or piracetam. A single RCT reported that serum neuron-specific enolase (NSE) levels were significantly reduced (p = 0.009) in the memantine compared to the control group, and this coincided with reported significant day-to-day improvements in Glasgow Coma Scale (GCS) for patients receiving memantine. The remaining RCTs investigated the effects of memantine on cognitive function using 26 standardized tests for assessing cognition function. One RCT reported significant improvements in cognitive function across all domains whilst the other two RCTs, reported that patients in the memantine group underperformed in all cognitive outcome measures. This review shows that despite laboratory and clinical evidence reporting reduced serum NSE and improved GCS, supporting the existence of the neuroprotective properties, there is a lack of reported evidence from RCTs to suggest that memantine directly leads to cognitive improvements in TBI patients.
Effects of acetylcholinesterase inhibitors on cognitive function in patients with chronic traumatic brain injury: A systematic review