Citicoline for traumatic brain injuries: A systematic review and implications for future research

Background and Objectives: Traumatic brain injury (TBI) is a catastrophic condition that exerts a high burden on individuals, families, and societies. The objective of this study was to systematically review the human studies on the efficacy and safety of citicoline for the management of TBIs. Materials and Methods: Relevant articles were identified by searching PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials on July 1, 2022. Results: Eighteen studies met the predefined eligibility criteria, including 12 randomized controlled trials (RCTs). Citicoline was administered via injectional (n = 11, 61.1%), enteral (n = 5, 27.8%), both injectional and enteral (n = 1, 5.5%), and unknown (n = 1, 5.5%) routes. Numerically, studies reporting the favorable impact of citicoline on patient outcome outnumbered (n = 13, 72.2%). However, the largest RCT could not demonstrate positive results. Only two studies reported complications, and the observed difference between citicoline and placebo groups was not statistically significant in either of them. Conclusion: Despite promising results in animal studies, human studies have shown inconsistent results regarding the role of citicoline in TBI management. Homogeneity of patients, subgroups of patients who might benefit more, the efficacy of citicoline as a part of combination therapies, and factors that could potentially influence the pharmacokinetics and brain uptake of citicoline should be considered when designing future studies.