The cognitive effects of esketamine: what do we know so far?
European Psychiatry June 1, 2022 DOI: 10.1192/j.eurpsy.2022.1879 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Population | 24 healthy individuals and 802 patients with treatment-resistant depression, drawn from randomized controlled trials |
| Intervention | Esketamine |
| Duration | One study assessed cognition pre- and postdose at 40 minutes, 2, 4, and 6 hours; another had a 1-year follow-up |
| Topics | Esketamine |
| Key findings | Across the randomized trials reviewed, intranasal esketamine produced a brief cognitive decline at 40 minutes postdose in healthy participants that resolved by 2 hours, while one-year data in 802 treatment-resistant depression patients showed stable or slightly improved cognition in those under 65 and mostly stable or improved performance in those 65 and older, except for slowing simple and choice reaction times from week 20. The authors conclude esketamine is a promising treatment for treatment-resistant depression and call for larger trials to clarify short- and long-term cognitive effects. |
Abstract
IntroductionEsketamine is an S-enantiomer of ketamine approved by the EMA for treatment-resistant depression (TRD). As an NMDA receptor antagonist, its administration results in increase of glutamate release and AMPA receptor activation, supporting both rapid-onset and long-term antidepressant effects. Short-term tolerability seems acceptable but major concerns remain regarding long-term safety, specifically regarding potential neurocognitive toxicity.ObjectivesTo clarify the potential short and long-term cognitive beneficial-effects and side-effects of esketamine.MethodsResearch was made using the Medline database, through the Pubmed search engine, using the keywords: “esketamine”, “cognition”. Only randomized-controlled trials were considered.ResultsOne study focused on the effects of intranasal esketamine (INE) on cognitive functioning in 24 healthy individuals, who were evaluated pre- and postdose (40 min, 2h, 4h and 6h). The results showed a decline in cognitive performance at 40 min postdose, returning to comparable levels as placebo by 2h postdose. Another study, with a follow-up of 1 year, involving 802 TRD patients, accessed the long-term safety of INE. In patients aged <65 years-old, performance on all cognitive tests remained stable or slightly improved from baseline during long-term treatment. In patients ≥ 65 years-old, the mean performance on all tests improved or remained stable, while the simple and choice reaction time began slowing at week 20.ConclusionsEsketamine has proven to be a promising new option for the treatment of TRD and available studies have shown promising results regarding patients’ cognitive function. Larger clinical trials are needed to further evaluate its short-term and long-term cognitive effects.DisclosureNo significant relationships.