Current neuropharmacology
January 1, 2025
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati et al.
23 citations
Among patients with treatment-resistant depression who continued esketamine nasal spray for at least six months, 76.2% responded or achieved remission. Of those who had not responded by six months, a subset improved by twelve months. Side effects occurred in 71.8% of patients at six months, decreasing to 42% at twelve months; the most common were sedation and dissociation. Only two patients stopped treatment due to tolerability issues. The findings suggest esketamine is effective and safe for mid- to long-term treatment, with a novel observation of late clinical response in some patients. Results require confirmation in larger samples and longer observation periods.
Frontiers in psychiatry
January 1, 2025
Miriam Olivola, Filippo Mazzoni, Barbara Tarantino et al.
7 citations
In treatment-resistant depression, esketamine—a glutamatergic modulator approved in 2019—may improve not only depressive symptoms but also key psychological factors such as mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. In a six-month observational study of 36 patients with treatment-resistant depressive episodes, depressive symptoms significantly decreased, as measured by the Montgomery-Åsberg Depression Rating Scale. By six months, 69% of patients achieved remission, indicating a robust and sustained response. The findings suggest esketamine may be particularly beneficial in reducing cognitive rigidity and improving mentalization, potentially breaking the inflexible thinking patterns that sustain depression. Personalized treatment approaches are emphasized.
Asian journal of psychiatry
June 1, 2026
Fabiola Raffone, Filippo Mazzoni, Arianna De Ciechi et al.
3 citations
In a six-month observational study of 90 outpatients with treatment-resistant depression receiving intranasal esketamine, those with and without comorbid borderline personality disorder showed sustained reductions in suicidal ideation, suicidal behavior, and deliberate self-harm. Improvements were significant from month one onward. Self-harm episode frequency in the borderline group dropped from a mean of 30.8 at baseline to 2.4 at six months. Baseline impulsivity correlated with self-harm and suicidal measures, but these associations weakened by six months. No serious adverse events, treatment discontinuations, or increases in suicidality occurred. Controlled studies are needed to confirm durability, especially for patients with borderline personality disorder.
Brain Sciences
February 7, 2026
Miriam Olivola, Tiziano Prodi, Giada Versaci et al.
2 citations
During intranasal esketamine treatment for treatment-resistant depression, patients describe four distinct types of dissociative experiences: sensory alteration and perceptual flow (27.8%), time suspension and chronological drift (58.3%), body and space alteration (55.6%), and psychic distance from suffering (83.3%). Most patients frame these experiences as neutral or meaningful, often linked to temporary relief from rumination and depressive distress, though a minority report transient distress or loss of control. The findings suggest dissociation functions as a transitional subjective state whose clinical relevance depends on anticipation, framing, monitoring, and integration, supporting structured psychoeducation and in-session support in esketamine programs.
Psychiatry research
June 16, 2026
Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi et al.
Among 90 outpatients with treatment-resistant depression, half also had borderline personality disorder (BPD). Depressive symptoms, measured by the MADRS scale, improved substantially over six months of intranasal esketamine treatment. The BPD group showed faster early improvement, and from one month onward had higher response rates (≥50% reduction in symptoms). Remission rates at six months were similar between groups (48.9% with BPD vs. 57.8% without). Anxiety and impulsivity decreased across the whole sample, and cognitive function did not worsen. No serious adverse events or dropouts occurred. Comorbid BPD did not hinder the overall remission outcome.
European psychiatry : the journal of the Association of European Psychiatrists
June 10, 2026
Riccardo Guglielmo, Miriam Olivola, Alberto Inuggi et al.
Over six months of routine esketamine treatment for treatment-resistant depression, depressive symptoms and daily functioning both improved progressively. By month six, 78.3% of patients showed a symptomatic response and 46.7% reached symptomatic remission, while 78.3% showed a functional response but only 33.3% achieved functional remission. Functional remission accumulated more slowly than symptomatic remission, with cumulative rates of 5% at one month, 15% at three months, and 33.3% at six months. Higher baseline disability and more previous antidepressant trials were linked to lower odds of functional remission at six months. The findings suggest that functional improvement follows a distinct trajectory from symptom improvement and should be monitored separately in treatment-resistant depression.
Journal of clinical psychopharmacology
March 24, 2026
Riccardo Guglielmo, Emma Laura Facchinetti, Daniele Cioci et al.
Treatment-resistant depression, affecting up to one third of people with major depressive disorder, often involves lasting cognitive problems that hinder recovery. A systematic review of six studies found that esketamine does not appear to cause cognitive decline in adults aged 18 to 80. Improvements in attention and processing speed were the most frequent and robust findings, seen in both randomized trials and naturalistic studies. Memory remained stable in short-term studies but improved with longer follow-up. Executive functions improved mainly in participants with baseline impairments and in long-term assessments. Overall, esketamine appears cognitively safe and may offer selective cognitive benefits, particularly in attention and processing speed, potentially supporting functional recovery.
Clinics and practice
March 13, 2026
Alessandro Guffanti, Matteo Leonardi, Natascia Brondino et al.
In three young adults (ages 20–25) with mild to moderate autism spectrum disorder and treatment-resistant depression, intranasal esketamine added to standard antidepressants reduced depressive symptoms. Two patients achieved clinical remission at six months, and one showed partial response. Suicidal ideation decreased, but mentalization and social cognition improved only mildly. Subjective quality of life rose substantially for all three. No major side effects occurred. These preliminary observations require confirmation in controlled trials.
Preprints.org
January 15, 2026
A. Guffanti, Matteo Leonardi, Natascia Brondino et al.
preprint
Intranasal Esketamine, when added to standard antidepressants, reduced depressive symptoms in three young adults with both treatment-resistant depression and autism spectrum disorder. Two patients achieved full remission and one showed partial remission over six months, with no major side effects. Suicidal thoughts decreased, but abilities related to understanding others' mental states improved only slightly. Quality of life scores rose substantially for all three patients. The authors note the small sample prevents statistical conclusions and call for larger, randomized studies.
Journal of Clinical Medicine
December 29, 2025
Matteo Leonardi, Alice Frediani, Mauro Angeletti et al.
Intranasal esketamine rapidly reduces suicidal ideation and depressive symptoms in patients with treatment-resistant depression. Suicidal ideation scores dropped from 1.56 at baseline to 0.78 after one week and to 0.12 after six months. Depressive symptoms improved from a mean Montgomery-Åsberg Depression Rating Scale score of 30.9 at baseline to 17.5 after one week and 9.8 after six months. Male gender was a negative predictor of response; no other baseline variable predicted outcomes. The findings suggest intranasal esketamine is effective for rapid reduction and resolution of suicidal ideation in this population, and gender differences should be considered in treatment planning.