Evidence map›Paper›PMID 42164345›Full record

ArticleFrontiers in pharmacology2026

Pilot study on esketamine response in treatment-resistant depression: impact of pharmacogenetic, clinical, and demographic variables.

Michaela Krivosova, Matteo Marcatili, Gessica Guerrera, Ranieri Domenico Cornaggia, Federico Luigi Motta, Tommaso Paolini, Beatrice Gamba, Emanuela Giampieri, Francesca Bertola, Beatrice Benatti and 1 more

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Michaela Krivosova *Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovakia.
Matteo Marcatili *Department of Mental Health, Fondazione IRCSS San Gerardo dei Tintori, Monza, Italy.
Gessica GuerreraSchool of Medicine and Surgery, University of Messina, Messina, Italy.
Ranieri Domenico CornaggiaSchool of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Federico Luigi MottaSchool of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Tommaso PaoliniSchool of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Beatrice GambaSchool of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Emanuela GiampieriDepartment of Mental Health, Fondazione IRCSS San Gerardo dei Tintori, Monza, Italy.
Francesca BertolaCytogenetics and Medical Genetics Unit, Centre for Disorders of Iron Metabolism, San Gerardo Hospital, Fondazione IRCSS San Gerardo dei Tintori, Monza, Italy.
Beatrice BenattiDepartment of Biomedical and Clinical Sciences Luigi Sacco, Department of Psychiatry, ASST Fatebenefratelli-Sacco, CRC 'Aldo Ravelli' for Neurotechnology & Experimental Brain Therapeutics, University of Milan, Milan, Italy.
Massimo ClericiDepartment of Mental Health, Fondazione IRCSS San Gerardo dei Tintori, Monza, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Esketamine, the S-enantiomer of ketamine, is a rapid-acting antidepressant approved for treatment-resistant depression (TRD) when used in combination with an oral antidepressant. Identifying reliable clinical or genetic predictors of treatment response remains a critical unmet need. This study aimed to evaluate the impact of selected clinical and genetic variables on esketamine response in a real-world TRD cohort. Methods: Thirty-two TRD patients received intranasal esketamine over 2 months (12 administrations) and underwent pharmacogenetic testing. Depressive symptoms were assessed at baseline and at each session. Response and remission rates were analyzed in relation to clinical, demographic, and genetic variables, including Results: No single demographic, clinical, or genetic variable reliably predicted treatment response. Adjunctive psychotherapy emerged as the only factor significantly associated with remission. Because most patients reached the standard 84 mg dose under the protocol, nominal dosing explained little of the observed variability in outcomes. Exploratory analyses suggested that metabolic phenotype and concomitant pharmacotherapy may contribute to inter-individual differences in treatment response. Discussion and Conclusions: In real-world TRD care, variability in esketamine response appears to be driven less by patient selection or nominal dose and more by a combination of pharmacologic exposure, biological factors, and psychotherapeutic engagement. These findings support a multidimensional, clinically oriented approach to treatment optimization rather than reliance on a single predictor. Given the limited sample size, the study may have been underpowered to detect modest associations, and the results should be therefore considered exploratory. Future research should prioritize the co-optimization of dosing strategies and psychotherapeutic engagement in routine care, and confirm these findings in larger, prospective studies.

Indexed as

BDNFCYP2B6esketamineOPRM1pharmacogeneticspsychotherapyTRDtreatment-resistant depression

Identifiers

PMID42164345
PMCPMC13185135

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