Auto-Induction in Oral Esketamine Treatment for Treatment-Resistant Depression: An Exploratory Study.
Pharmaceuticals (Basel, Switzerland) April 25, 2025 Jolien K E Veraart, Cornelis F Vos, Nieko C Punt et al. 2 citations
In patients with treatment-resistant depression receiving oral esketamine for six weeks, plasma concentrations of esketamine and noresketamine on day 39 were 59% and 35% lower than predicted by a pharmacokinetic model. This suggests that auto-induction of drug-metabolizing enzymes CYP3A4 and CYP2B6 occurs, which may explain the diminished therapeutic effects and side effects observed with long-term use. Identifying auto-induction as a mechanism of tolerance could have important clinical implications for maintaining efficacy.