Current neuropharmacology
January 1, 2025
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati et al.
23 citations
Among patients with treatment-resistant depression who continued esketamine nasal spray for at least six months, 76.2% responded or achieved remission. Of those who had not responded by six months, a subset improved by twelve months. Side effects occurred in 71.8% of patients at six months, decreasing to 42% at twelve months; the most common were sedation and dissociation. Only two patients stopped treatment due to tolerability issues. The findings suggest esketamine is effective and safe for mid- to long-term treatment, with a novel observation of late clinical response in some patients. Results require confirmation in larger samples and longer observation periods.
Frontiers in psychiatry
January 1, 2025
Miriam Olivola, Filippo Mazzoni, Barbara Tarantino et al.
7 citations
In treatment-resistant depression, esketamine—a glutamatergic modulator approved in 2019—may improve not only depressive symptoms but also key psychological factors such as mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. In a six-month observational study of 36 patients with treatment-resistant depressive episodes, depressive symptoms significantly decreased, as measured by the Montgomery-Åsberg Depression Rating Scale. By six months, 69% of patients achieved remission, indicating a robust and sustained response. The findings suggest esketamine may be particularly beneficial in reducing cognitive rigidity and improving mentalization, potentially breaking the inflexible thinking patterns that sustain depression. Personalized treatment approaches are emphasized.
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.