Plasma esketamine and noresketamine levels and antidepressant response with oral esketamine treatment
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: Oral esketamine has relatively low and variable bioavailability, which may complicate broader use as an antidepressant. This study aimed to investigate associations between different pharmacokinetic outcomes and change in depressive symptoms following oral esketamine administration in patients with treatment-resistant depression. Understanding such associations may inform dosing and administration strategies in clinical practice. Oral esketamine was administered twice weekly for six weeks using a titration approach in 17 patients. Esketamine and noresketamine serum levels were measured 30 min and 60 min after esketamine administration. Change in depression severity was plotted against the serum levels of esketamine and noresketamine, their sum and their ratios. We observed high inter-individual variability in oral esketamine pharmacokinetics, and we found no association between depressive symptom change and the pharmacokinetic outcomes. The small sample size and flexible-dose regimen complicate definitive conclusions. In the treatment of depression, clinical response may not correspond to esketamine pharmacokinetic outcomes. Individually-based titration strategies based on clinical antidepressant effects appear to be the optimal approach moving forward. • Oral esketamine could be an alternative treatment option for TRD • The relationship between esketamine concentrations and clinical response is unknown • Oral esketamine pharmacokinetics showed high inter-individual variability • We observed no link between (nor)esketamine levels and antidepressant response
Source: European Journal of Pharmacology
Institutions: University Medical Center Groningen, University of Groningen, PsyQ
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,230
OpenAlex ID: W4408225330