N-methyl-D-aspartate receptor antagonists in improving cognitive deficits following traumatic brain injury: a systematic review.

OBJECTIVE

To review the role of N-methyl-D-aspartate receptor (NMDAR) antagonists in managing post-TBI cognitive deficits.

METHODS

A search of PubMed, Embase, and Cochrane was conducted on Jan 12, 2021 without publication date or language restriction.

RESULTS

Forty-seven studies were included, involving 20 (42.6%) randomized controlled trials. Four (8.5%) studies had a low risk of bias (RoB), while 34 (72.3%) had unclear and nine (19.2%) had high RoB. Six NMDAR antagonists had been investigated: amantadine (n = 32), memantine (n = 4), magnesium (n = 4), traxoprodil (n = 3), selfotel (n = 2), and dextromethorphan (n = 2).

CONCLUSION

Although some benefits were observed, there are still some concerns regarding the efficacy and safety of NMDAR antagonists in improving post-TBI cognitive deficits. Further research is required to examine whether (i) these agents, notably amantadine, could accelerate cognitive improvement and shorten the hospital stay, (ii) these agents affect different cognitive domains/subdomains in the same direction, (iii) an optimal therapeutic time window exists, (iv) a member of this drug class can be proved to be effective without interfering in non-excitotoxic actions of glutamate, (v) they can be more effective as part of combination therapies or in particular subgroups of patients with TBI.