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Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING)

Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea, Luisa de Risio, Antea D’Andrea, Stefania Chiappini, Rosalba Carullo, Sergio Barlati, Raffaella Zanardi, Gianluca Rosso, Sergio De Filippis, Marco Di Nicola, Ileana Andriola, Matteo Marcatili, Giuseppe Nicolò, Vassilis Martiadis, Roberta Bassetti, Domenica Nucifora, Pasquale De Fazio, Joshua D. Rosenblat, Massimo Clerici, Bernardo Maria Dell’osso, Antonio Vita, Laura Marzetti, Stefano L. Sensi, Giorgio Di Lorenzo, Roger S McIntyre, Giovanni Martinotti

Psychiatry Research July 29, 2023 DOI: 10.1016/j.psychres.2023.115378 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Retrospective, multicentric, real-world study Peer reviewed
Sample size 149
Population Treatment-resistant depression patients
Intervention Esketamine Nasal Spray
Duration Three months post-treatment initiation
Topics Anxiety Depression Esketamine
Keywords Rating scale Depression economics Anhedonia Clinical psychology Mood Schizophrenia object-oriented programming Developmental psychology
Citations 56
Key points Machine learning classifiers predicted response to esketamine nasal spray in treatment-resistant depression with accuracies of 68.53% at one month and 66.26% at three months, and remission at three months with 68.60% accuracy.

Abstract

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • Machine learning classifiers predicted esketamine response with about 66-69% accuracy, and features such as anxious distress positively predicted response and remission.

    Synthesized

Comparable studies

Other observational and cohort studies on esketamine for anxiety, most cited first.

Study Year Design Participants
Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression Patients with treatment-resistant bipolar depression (B-TRD) and unipolar... 2023 Observational cohort n = 70
Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study Patients with treatment-resistant depression and a substance use disorder 2023 Observational, retrospective, multicentre study n = 26
Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group Adults aged 65 years or older with treatment-resistant depression 2023 Post-hoc analysis of a multicenter, retrospective, observational study n = 30
Perioperative esketamine exposure and postoperative depression and anxiety in elderly patients undergoing joint replacement surgery: a retrospective cohort study Elderly patients aged 65–80 years undergoing unilateral hip or knee joint replacement... 2026 Retrospective cohort study n = 60
Is the reduction in suicidal ideation and deliberate self-harm during intranasal esketamine treatment independent of antidepressant response? A secondary, longitudinal analysis of a real-world TRD cohort with and without comorbid borderline personality disorder Real-world esketamine cohort enriched for comorbid borderline personality disorder 2026 Secondary analysis of a longitudinal cohort

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