The Efficacy and Safety of Animal-Derived Nootropics in Neurocognitive Disorders: A Systematic Review and Meta- Analysis of Randomised Controlled Trials.

Abstract

Background: Animal-derived nootropics, Cerebrolysin, Actovegin and Cortexin, represent a promising approach in treating neurocognitive disorders (NCDs). These drugs are widely utilised internationally to treat neurological conditions; however, evidence supporting their clinical significance is controversial. Aim: To critically appraise available evidence using contemporary methods and provide an updated systematic and quantitative assessment on the efficacy and safety of animal-derived nootropics in treating NCDs, based on clinical trials. Methods: Seven databases were searched to identify trials evaluating the effects of animal-derived nootropics. The quality and strength of evidence were critically appraised using the risk of bias (RoB-2) and GRADE assessment tools. Due to the limited number of eligible studies for Actovegin and Cortexin, all conducted meta-analyses solely evaluated Cerebrolysin. Results: The meta-analyses suggested Cerebrolysin to be potentially beneficial in improving cognitive (SMD: -0.16, 95% CI: -0.31 to -0.01; P=0.03) and global function (OR: 2.64, 95% CI: 1.17 to 5.98; P=0.02). Furthermore, the difference in adverse event incidence rates was comparable to placebo (RR: 0.96, 95% CI 0.78 to 1.18; P=0.67), suggesting Cerebrolysin to be safe. Similarly, Actovegin and Cortexin were suggested to be safe and potentially beneficial in improving cognition. However, across the included studies, the risk of bias was moderate to high and certainty of evidence was considered low to very low. Conclusion: Although the findings suggested animal-derived nootropics to be safe and exhibit minimal to modest efficacy in treating NCDs, available evidence posed many quality concerns, and therefore, is not sufficiently convincing to change medical practices.