Pilot study on esketamine response in treatment-resistant depression: impact of pharmacogenetic, clinical, and demographic variables.
Frontiers in pharmacology January 1, 2026 Michaela Krivosova, Matteo Marcatili, Gessica Guerrera et al.
In a real-world group of 32 patients with treatment-resistant depression receiving intranasal esketamine over two months, no single demographic, clinical, or genetic variable—including BDNF (rs6265), OPRM1 (rs1799971) polymorphisms, or CYP2B6, CYP2C9, and CYP3A4 metabolizer status—reliably predicted treatment response. Adjunctive psychotherapy was the only factor significantly associated with remission. Most patients received the standard 84 mg dose, so nominal dosing explained little of the outcome variability. Exploratory analyses suggested that metabolic phenotype and concomitant pharmacotherapy may contribute to inter-individual differences. The findings support a multidimensional, clinically oriented approach to optimizing esketamine treatment rather than relying on a single predictor. The small sample size may have limited the ability to detect modest associations, so results are exploratory.