Frontiers in PsychiatrySeptember 15, 2026Serena Chiara Civardi, Filippo Besana, Federico Durbano et al.
Background Treatment-resistant depression (TRD) is a major clinical challenge, with many patients failing to respond to conventional antidepressants. Psychedelic compounds such as psilocybin and ayahuasca have recently gained attention as potential rapid-acting therapies. Beyond their neurobiological effects, methodological, ethical, and real-world applicability concerns are critical for...
Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without...
Esketamine has demonstrated efficacy in treatment-resistant depression (TRD), but medium-term real-world functional outcomes remain understudied. This study described 6-month depressive symptoms and functional trajectories during routine esketamine treatment, focusing on functional outcomes and remission correlates. In this prospective multicenter study, 60 patients with TRD initiating...
Suicidal ideation and deliberate self-harm are frequent and persistent in treatment-resistant depression (TRD), particularly when comorbid borderline personality disorder (BPD) is present. Real-world evidence on antisuicidal outcomes during intranasal esketamine in this population remains limited. In this multicentre prospective observational study, 90 outpatients with TRD received intranasal...
Introduction Intranasal esketamine has emerged as an innovative treatment for TRD due to its rapid antidepressant effects. However, the clinical response is heterogeneous, and growing evidence suggests that comorbid personality disorders (PDs) may significantly shape treatment outcomes. Although PDs are frequently diagnosed in TRD patients, little is known about their differential influence on...
Introduction Esketamine-induced dissociation is a transient, pharmacologically mediated alteration in consciousness, often distinct from pathological dissociation. While not required for clinical improvement, these states may engage neural circuits implicated in therapeutic change. Objectives This study explores patients’ lived experiences of dissociation as potentially meaningful transitional...
Introduction Treatment-resistant depression (TRD) is a severe condition associated with high suicide risk and limited response to conventional antidepressants. Intranasal esketamine has shown rapid efficacy in reducing depressive symptoms and suicidal ideation. Objectives This observational study assessed the real-world effectiveness of esketamine in reducing suicidal ideation, self-harm...
Introduction The role of dissociation in mediating antidepressant response to intranasal esketamine remains debated. While dissociative experiences are often observed during treatment, their predictive value for clinical outcomes is uncertain. Objectives We aimed to assess whether (i) baseline dissociative traits (DES-II) and (ii) early changes in dissociation (ΔDES T0→T2) predict short-term...
Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no...
Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and...
Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pathological dissociation typically observed in trauma-related conditions. While most studies have quantified these effects using the Clinician-Administered Dissociative States Scale (CADSS), patients' subjective phenomenology and meaning-making remain...
Background: Suicidal ideation (SI) represents a clinical challenge in patients with treatment-resistant 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...
INTRODUCTION Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive...
Case Report Esketamine in Geriatric Depression and Pseudodementia: A Case Study Filippo Mazzoni 1,2, Giovanni Carnevale Miacca 1,2, Alessandro Guffanti 1,2, Vassilis Martiadis 3, Benardo Maria Dell’Osso 4,5,6,7, Natascia Brondino 1,2 and Miriam Olivola 1,4 1 Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy 2 Department of Mental Health and Addiction, ASST...
Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups. This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study...
Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, was approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes,...
Major depression is a common comorbidity in autism spectrum disorder (ASD), often difficult to identify and to treat. Autistic subjects are more at risk for suicidal thoughts and behaviors compared to typically developing peers. Unfortunately, ASD individuals are more frequently treatment-resistant and often show side-effects which reduce efficacy. Intranasal esketamine has been recently...