Effects of Memantine in Patients with Traumatic Brain Injury: A Systematic Review

Abstract

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 early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies

“…On the other hand, significant glutamate release results in magnesium loss in the glutamate receptor's ion channel. Consequently, neuronal cells depolarize, swell, and necrotize (Khan et al, 2021). Preclinical models indicate that glutamate-mediated excitotoxicity is pivotal in the secondary injury cascade.…”

Targets of Neuroprotection and Review of Pharmacological Interventions in Traumatic Brain Injury

“…Donepezil has also shown benefit in TBI patients in the sub-acute and chronic phase of recovery, with improved attention and short-term memory (Walker et al, 2004;Khateb et al, 2005). A recent systematic review of memantine in TBI patients cited evidence of improved serum NSE levels and improved GCS, however overall there was a lack of high quality RCTs demonstrating direct cognitive improvement (Khan et al, 2021). The potential shown in the early studies of these other AChE inhibiting compounds suggests value in continued exploration.…”