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.
Comparable studies
Other observational and cohort studies on esketamine for anxiety, most cited first.
Citations in the library
Cited by 25
- Esketamine Treatment Trajectory of Patients with Treatment-Resistant Depression in the Mid and Long-Term Run: Data from REAL-ESK Study Group. Current Neuropharmacology 2025
- Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada. Frontiers in Psychiatry 2023
- Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience) Journal of Personalized Medicine April 1, 2025
- Anhedonia in bipolar depression treated with ketamine Bipolar Disorders February 4, 2024
- Effectiveness of repeated Esketamine nasal spray administration on anhedonic symptoms in treatment-resistant bipolar and unipolar depression: A secondary analysis from the REAL-ESK study group. Psychiatry Research July 26, 2025
and 20 more in the library
Cites 23
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
and 18 more in the library