Psychopathology
January 1, 2024
Pietro Sarasso, Martina Billeci, Irene Ronga et al.
18 citations
Dissociative experiences from ketamine, often seen as undesirable side effects, may be essential for its antidepressant action in certain depression subtypes. The 'relaxed prior hypothesis' proposes that ketamine enhances sensitivity to bodily signals by blocking glutamate, improving short-term plasticity. Two patients with 'depersonalized depression' (Entfremdungsdepression) in a six-month esketamine program showed that induced dissociation, particularly disembodiment, could suspend ingrained patterns of feeling and behavior. This creates a window of psychological plasticity, allowing the body to regain responsiveness to emotional cues. The findings suggest esketamine's dissociative effects may be especially beneficial for those with compromised interoceptive awareness and interaffectivity.
Journal of Clinical Medicine
February 20, 2026
Vassilis Martiadis, Fabiola Raffone, Serena Testa et al.
7 citations
Intranasal esketamine provides rapid symptom relief for treatment-resistant depression when standard antidepressants fail, but its real-world effectiveness depends on organizational and multidisciplinary factors beyond pharmacology. This narrative review synthesizes clinical and real-world evidence to propose a phase-based integration framework that specifies complementary roles for psychiatry, nursing, and psychotherapy across pre-treatment assessment, induction, session delivery, post-session integration, and maintenance phases. The framework emphasizes safety, continuity of care, and patient-centred monitoring, with measurable implementation indicators. While evidence supports esketamine's efficacy in reducing depressive symptoms, anhedonia, and suicidality, prospective implementation studies are needed to evaluate clinical effectiveness, feasibility, and cost-effectiveness of the proposed multidisciplinary approach.
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.
Behavioral sciences (Basel, Switzerland)
May 14, 2026
Fabiola Raffone, Carlo Ignazio Cattaneo, Enrico Pessina et al.
Trauma-related autobiographical memories can become intrusive and distressing, contributing to post-traumatic stress disorder (PTSD) and depression, including treatment-resistant depression (TRD). Intranasal esketamine, an approved rapid-acting treatment for TRD, may create conditions that facilitate psychotherapeutic work on traumatic memories. This narrative review synthesizes evidence on ketamine and esketamine for PTSD and trauma symptoms, distinguishing intravenous ketamine studies, intranasal esketamine data, and combination approaches with psychotherapy.