Effectiveness of Intranasal Esketamine on Suicidal Ideation and Depressive Symptoms - A Longitudinal Study

Q: What is the primary goal of this longitudinal study?

To evaluate the efficacy of intranasal esketamine on suicidal ideation and depressive symptoms and to identify potential predictors of clinical response.

Q: How were suicidal ideation and depressive symptoms measured?

Suicidal ideation was assessed with the Columbia Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated with the Montgomery–Åsberg Depression Rating Scale (MADRS).

Q: What predictor was found for treatment response?

Male sex predicted lower odds of early response on the C-SSRS, while no other baseline variable showed significance as a predictor.

Sep 30, 2026

Uploaded by Aditya

Intranasal esketamine is evaluated for its ability to rapidly reduce suicidal ideation and depressive symptoms in patients with treatment-resistant depression, using real-world, longitudinal evidence. The study assesses efficacy with C-SSRS and MADRS at baseline and at five follow-ups (1 week through 6 months), while collecting sociodemographic, clinical, and pharmacological variables. In 80 enrolled patients, suicidal ideation and depressive severity decline significantly, with a higher proportion achieving SI and MADRS response over time.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background, Aims, Methods

Results and Conclusions

Introduction

Article Effectiveness of Intranasal Esketamine on Suicidal Ideation and Depressive Symptoms in Patients with Treatment-Resistant Depression: A Longitudinal Study Matteo Leonardi 1, Alice Frediani 1, Maria Chiara Angeletti 1, Monica Biseo 1, Giada Versaci 1, Michele Castiglioni 1, Miriam Olivola 1,2, *, Matteo Vismara 1, Alberto Varinelli 1, Monica Bosi 1, Beatrice Benatti 1, Natascia Brondino 2 and Bernardo Maria Dell’osso 1,3,4,5 Academic Editor: Silvia Cimino Received: 11 November 2025 Revised: 13 December 2025 Accepted: 27 December 2025 Published: 29 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Psychiatry, ASST Fatebenefratelli Sacco, University of Milan, 20157 Milan, Italy; [matteo.leonardi@unimi.it](matteo.leonardi@unimi.it) (M.L.); [frediani.alice@asst-fbf-sacco.it](frediani.alice@asst-fbf-sacco.it) (A.F.); [angeletti.maria@asst-fbf-sacco.it](angeletti.maria@asst-fbf-sacco.it) (M.C.A.); [monica.biseo@unimi.it](monica.biseo@unimi.it) (M.B.); [versaci.giada@gmail.com](versaci.giada@gmail.com) (G.V.); [castiglioni.michele@asst-fbf-sacco.it](castiglioni.michele@asst-fbf-sacco.it) (M.C.); [vismara.matteo@asst-fbf-sacco.it](vismara.matteo@asst-fbf-sacco.it) (M.V.); [varinelli.alberto@asst-fbf-sacco.it](varinelli.alberto@asst-fbf-sacco.it) (A.V.); [bosi.monica@asst-fbf-sacco.it](bosi.monica@asst-fbf-sacco.it) (M.B.); [dellosso.bernardo@asst-fbf-sacco.it](dellosso.bernardo@asst-fbf-sacco.it) (B.M.D.) 2 Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy; [natascia.brondino@unipv.it](natascia.brondino@unipv.it) 3 Department of Biomedical and Clinical Sciences, Neuroscience Research Center, University of Milan, 20157 Milan, Italy 4 Bipolar Disorders Clinic, Department of Psychiatry and Behavioral Sciences, Stanford Medical School, Stanford University, Stanford, CA 94305, USA 5 “Aldo Ravelli” Center for Neurotechnology and Brain Therapeutic, University of Milan, 20157 Milan, Italy * [Correspondence: miram.olivola@asst-fbf-sacco.it](Correspondence: miram.olivola@asst-fbf-sacco.it) Abstract Background: Suicidal ideation (SI) represents a clinical challenge in patients with treatmentresistant depression (TRD), and the management of this condition should be as rapid and effective as possible. Intranasal Esketamine has shown promise in patients with TRD due to its rapid onset of action on both SI and depressive symptoms. Since this medication has been recently approved, real-world data on its efficacy remain scarce, and little is known about which patients are most likely to benefit from this approach. Aims: This study aimed (1) to evaluate the efficacy of intranasal Esketamine on SI and depressive symptoms and (2) to find potential predictors of clinical response. Methods: Patients with TRD who received intranasal Esketamine were included in this study. Clinical evaluationsand psychometric assessments were made at baseline (T0) and at five subsequent time points (one week [T1], one month [T2], two months [T3], three months [T4], and six months [T5]) . SI was assessed using the Columbia Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS) . Furthermore, sociodemographic, clinical, and pharmacological data were collected. Results: Eighty patients diagnosed with TRD were enrolled. Suicidal ideation (CSSRS items 1–5) decreased from 1.56 ± 1.65 at baseline to 0.78 ± 1.28 at T1 and 0.12 ± 0.52 at T5 (all p < 0.001) . MADRS fell from 31.81 ± 7.94 to 23.62 ± 9.08 and 10.19 ± 7.33 at the same time points (all p < 0.001) . By T1, 68.4% achieved an SI response on the C-SSRS. The MADRS response rate increased from 16.7% at T1 to an overall response of 62.5% at T5 . Male sex predicted lower odds of early

FAQs

What is the primary goal of this longitudinal study?

To evaluate the efficacy of intranasal esketamine on suicidal ideation and depressive symptoms and to identify potential predictors of clinical response.

How were suicidal ideation and depressive symptoms measured?

Suicidal ideation was assessed with the Columbia Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated with the Montgomery–Åsberg Depression Rating Scale (MADRS).

What predictor was found for treatment response?

Male sex predicted lower odds of early response on the C-SSRS, while no other baseline variable showed significance as a predictor.

Sep 30, 2026

Uploaded by Aditya