Psychiatry International
September 10, 2026
Tommaso Barlattani, Giorgio Sernia, Chiara D’Amelio et al.
Background: Evidence for repeated intranasal esketamine in obsessive–compulsive disorder (OCD) remains preliminary, particularly when OCD co-occurs with treatment-resistant depression (TRD). Methods: We report a 58-year-old woman treated with intranasal esketamine in routine clinical care for TRD; change in obsessive–compulsive symptoms was followed as a secondary observational outcome. Her...
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
July 17, 2026
Allan H. Young, Bernhard T Baune, Beatrice Benatti et al.
Esketamine nasal spray (NS) is an established treatment for patients with treatment resistant depression (TRD). To further optimise real-world outcomes, consensus is needed regarding strategies to enhance patient outcomes and decision-making factors for pivotal timepoints in esketamine NS treatment. This modified Delphi panel (3 rounds) established expert consensus (≥80% agreement) from 30...
The Lancet Regional Health - Europe
July 15, 2026
Vassilis Martiadis
The question of whether the striking antidepressant effects of psilocybin reported in randomised trials can be reproduced in everyday care remains largely unanswered. This is because those trials enrol highly selected patients, withdraw concomitant medication and deliver treatment under tightly standardised protocols. In this issue, Jungwirth et al. provide one of the first responses from...
Open MIND
July 13, 2026
Vassilis Martiadis, Fabiola Raffone
In acute trials of intravenous and intranasal ketamine/esketamine, the rapid anti-suicidal effect appears to be at least partly independent of the overall antidepressant response. That question has, to our knowledge, never been examined in a real-world esketamine cohort followed for six months, nor in a sample enriched for comorbid borderline personality disorder (BPD), a population excluded...
Clinical Neuropsychopharmacology and Addiction
June 25, 2026
Luca Persico, Giacomo D’andrea, Clara Cavallotto et al.
Background: Intranasal esketamine (ESK-NS) is an effective treatment for treatment-resistant depression (TRD), but whether antidepressant outcomes differ by sex and age remains insufficiently explored. Methods: This secondary analysis of the REAL-ESK study included 210 patients with TRD treated with ESK-NS in routine clinical practice and assessed at baseline (T0), one month (T1), and three...
Psychiatry Research
June 16, 2026
Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi et al.
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...
Asian Journal of Psychiatry
June 1, 2026
Fabiola Raffone, Filippo Mazzoni, Arianna De Ciechi et al.
3 citations
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...
Behavioral sciences (Basel, Switzerland)
May 14, 2026
Fabiola Raffone, Carlo Ignazio Cattaneo, Enrico Pessina et al.
Trauma-related autobiographical memories can manifest as involuntary, vivid, emotionally charged intrusions that perpetuate avoidance, negative emotions, and functional impairment. While these memories are central to post-traumatic stress disorder (PTSD), they also occur across diagnoses and are often reported in depressive disorders, including treatment-resistant depression (TRD). Although...
Clinics and practice
March 13, 2026
Alessandro Guffanti, Matteo Leonardi, Natascia Brondino et al.
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...
Journal of Clinical Medicine
February 20, 2026
Vassilis Martiadis, Fabiola Raffone, Serena Testa et al.
7 citations
Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providing rapid symptom relief when conventional antidepressant strategies fail. While its pharmacological efficacy has been demonstrated in randomized controlled trials, less attention has been paid to the organizational, relational, and multidisciplinary...
Brain Sciences
February 7, 2026
Miriam Olivola, Tiziano Prodi, Giada Versaci et al.
2 citations
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...
2026
Vassilis Martiadis, F. Raffone, Domenico de Berardis
BACKGROUND: Treatment-resistant depression (TRD) affects approximately one-third of patients with major depressive disorder and represents a critical clinical challenge. Esketamine (S-ketamine, Spravato), approved by FDA and EMA since 2019, and psychedelic-assisted therapies (psilocybin, MDMA) share a pharmacological feature unique among approved psychiatric treatments: they induce altered...
Current Neuropharmacology
October 20, 2025
Vassilis Martiadis, Fabiola Raffone, Danilo Atripaldi et al.
21 citations
Esketamine rapidly improved suicidality and depression in TRD, with preliminary evidence suggesting gender-specific responses, and highlighting the importance of tailored interventions to maximize outcomes. Further research is needed to confirm these differences, explore the long-term effects, and understand the underlying mechanisms.
Clinical Neuropsychopharmacology and Addiction
April 2, 2025
Filippo Mazzoni, Giovanni Carnevale Miacca, Alessandro Guffant et al.
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...
Current Neuropharmacology
2025
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati et al.
23 citations
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...
Frontiers in Psychiatry
2025
Miriam Olivola, Filippo Mazzoni, Barbara Tarantino et al.
7 citations
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,...
Frontiers in Psychiatry
2024
Matteo Di Vincenzo, Vassilis Martiadis, Bianca Della Rocca et al.
31 citations
Treatment-resistant depression (TRD) occurs when at least two different antidepressants, taken at the right dosage, for adequate period of time and with continuity, fail to give positive clinical effects. Esketamine, the S-enantiomer of ketamine, was recently approved for TRD treatment from U.S. Food and Drug Administration and European Medicine Agency. Despite proved clinical efficacy, many...
Psychopathology
2024
Pietro Sarasso, Martina Billeci, Irene Ronga et al.
18 citations
Dissociative experiences are considered undesirable ketamine's adverse events. However, they might be crucial for ketamine's antidepressant effects, at least in some depression subtypes. Current understandings of ketamine's therapeutic potentials converge on the so-called "relaxed prior hypothesis," suggesting that glutamatergic blockage up-weights bottom-up surprising somatosensory/affective...
Psychiatry Research
July 29, 2023
Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea et al.
56 citations
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...
American Journal of Geriatric Psychiatry
July 8, 2023
Giacomo D’andrea, Stefania Chiappini, Roger S McIntyre et al.
36 citations
INTRODUCTION: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still...