Clinical predictors of response to intranasal esketamine in treatment-resistant depression: a single-center real-world analysis from the Polish B.147 drug program

Background

Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder and remains a major contributor to disability and healthcare burden. Intranasal esketamine has demonstrated rapid antidepressant effects; however, clinically useful predictors of response are still lacking, limiting precision in patient selection. Real-world data provides a unique opportunity to investigate determinants of treatment response under routine clinical conditions. The Polish B.147 drug program, launched in 2023, enables reimbursed access to esketamine in a highly selected TRD population.

Aims

To evaluate real-world effectiveness and safety of intranasal esketamine and to identify clinical and biological predictors of treatment response in TRD.

Methods

This retrospective, single-center observational study included 30 adult patients with TRD treated with intranasal esketamine between July 2023 and January 2026 as part of the B.147 program.

Inclusion criteria were: age 18–75 years; recurrent depressive disorder (ICD-10 F33.1/F33.2) with MADRS ≥20; episode duration ≥6 months; failure of ≥2 (≤5) antidepressant trials in the current episode; ongoing SSRI/SNRI treatment; and electroconvulsive therapy contraindicated, ineffective, or declined. Exclusion criteria included bipolar disorder, borderline personality disorder, substance use disorders, pregnancy or breastfeeding, and clinically significant somatic contraindications.

Outcomes included response (≥50% reduction in MADRS at 4 weeks), remission (MADRS ≤10), and longitudinal changes in MADRS, PHQ-9, and VAS scores. Safety was assessed through adverse event monitoring. Predictor analyses applied Boruta feature selection to demographic, clinical, and laboratory variables, followed by logistic regression. Group comparisons used non-parametric tests.

Results

Baseline depression severity was high (mean MADRS 37). Esketamine treatment produced substantial symptom reduction. Among responders, mean MADRS decreased by 64.3% (24.6 points) after induction and 78.2% (29.9 points) after treatment completion. Parallel improvements were observed for PHQ-9 (−72.3% and −80.5%) and VAS (−57.9% and −64.2%).

At 4 weeks (end of induction phase), 73.9% of patients achieved response and 17.6% remission. Remission rates increased to 47% at treatment completion. Treatment was well tolerated, with predominantly transient, mild-to-moderate adverse events (dizziness, nausea, dissociation) and a 6% discontinuation rate due to adverse effects.

Feature selection consistently identified older age and duration of illness as relevant predictors, with platelet count emerging as a tentative biological correlate. Logistic regression did not yield statistically significant predictors, likely reflecting limited statistical power; however, longer illness duration showed a positive association with response (β=0.27, p=0.075). Baseline symptom severity did not differentiate responders from non-responders, suggesting that illness course and patient-level characteristics may be more informative than initial severity.

Conclusions

In this single-center real-world cohort, intranasal esketamine demonstrated robust effectiveness and favorable tolerability in TRD. Exploratory findings indicate that illness chronicity and demographic factors may influence treatment outcomes, supporting their consideration in patient stratification, while peripheral biomarkers warrant further validation. Despite strong clinical effectiveness, the B.147 program remains underutilized on the national scale, highlighting systemic barriers. Optimization of eligibility criteria, service accessibility, and clinical awareness may enhance implementation and support the development of data-driven, personalized treatment strategies.

References

No references