Adverse cognitive effects of glucocorticoids: A systematic review of the literature

Glucocorticoids as a drug class are widely used in the treatment of many conditions including more recently as one of the mainstay treatments for the SARS-CoV-2 infection. The physiological adverse effects are well described. However, less is known and understood about the potentially deleterious neuro-cognitive effects of this class of medication.

We carried out a systematic review of the literature using two separate search strategies. The first focussed on the rates of reporting of adverse cognitive effects of glucocorticoid use in randomised controlled trials. The second looked at those studies focussing directly on adverse cognitive effects associated with the use of glucocorticoids. MEDLINE, Embase and Cochrane Library was searched for randomised controlled trials utilising glucocorticoids as a part of a treatment regimen. Additionally, these databases were also used to search for articles looking directly at the adverse cognitive effects of glucocorticoids.

Of the forty-three RCTs included as a part of the first search strategy, only one (2.3%) included specific documentation pertaining to cognitive side effects. As a part of the twenty studies included in the second search strategy, eleven of the included studies (55%) were able to demonstrate a correlation between glucocorticoid use and decreased cognition. Most studies within this strategy showed that GCs predominately affected hippocampus-dependent functions such as memory, while sparing executive function and attention.

Overall, the data reporting of adverse clinical effects of glucocorticoid use is poor in recent RCTs. Given the demonstrable effect on predominately hippocampal-dependent cognitive functions evident within the literature, more thorough documentation is needed within clinical research to fully appreciate the potentially widespread nature of these effects.