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Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study

Miriam Olivola, Tiziano Prodi, Giada Versaci, Andrea Pignatti, Kevin la Monica, Fabiola Raffone, Nicolaja Girone, Natascia Brondino, Roberta Anniverno, Vassilis Martiadis, Giovanni Martinotti, Bernardo Dell’osso

Brain Sciences February 7, 2026 DOI: 10.3390/brainsci16020196 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Qualitative exploratory study Peer reviewed
Sample size 36
Population Adults with treatment-resistant depression receiving intranasal esketamine in outpatient settings in Northern Italy
Intervention Intranasal esketamine
Topics Anxiety Depression Esketamine
Keywords Dissociative experiences scale Dissociation chemistry Distress Exploratory research Thematic analysis Qualitative research Narrative Clinical psychology Psychotherapist Somatization Dissociative disorders Coping psychology Extrasensory perception Developmental psychology Interpretative phenomenological analysis Hypomania Thought suppression Psychosis
Citations 2
Key findings Patients describe four experiential domains of esketamine-induced dissociation, with psychic distance from suffering being the most common, and most narratives frame dissociation as neutral or subjectively meaningful rather than distressing.

Abstract

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 underexplored. This qualitative exploratory study investigated how patients narrate, interpret, and integrate dissociative experiences occurring during intranasal esketamine treatment for treatment-resistant depression (TRD).

Methods: We conducted semi-structured interviews with 36 adults with TRD who were receiving intranasal esketamine in outpatient settings in Northern Italy (2022-2024). Interviews focused on the most salient dissociative experiences during treatment. Transcripts were anonymized and analyzed using inductive thematic analysis. Two researchers coded the data independently; discrepancies were resolved by consensus, and recruitment continued until thematic saturation was reached.

Results: Four experiential domains emerged: sensory alteration and perceptual flow (10/36, 27.8%), time suspension and chronological drift (21/36, 58.3%), body and space alteration (20/36, 55.6%), and psychic distance from suffering (30/36, 83.3%). While a minority described transient distress or loss of control, most narratives framed dissociation as neutral or subjectively meaningful, often associated with a temporary reduction in ruminative self-focus and depressive distress.

Conclusions: A narrative, phenomenological lens complements quantitative research by clarifying what esketamine-induced dissociation feels like to patients and how it is appraised in context. The findings do not imply a causal or mediating role in antidepressant efficacy. Rather, they suggest that dissociation functions as a transitional subjective state, the clinical relevance of which depends on anticipation, framing, monitoring, and integration. These results support the use of structured psychoeducation, in-session support, and post-session integration within real-world esketamine programs.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • Patients described four experiential domains of esketamine-induced dissociation, with psychic distance from suffering being most common, and most framed dissociation as neutral or subjectively meaningful rather than distressing.

    Synthesized

Comparable studies

Other qualitative studies on esketamine, most cited first.

Study Year Design Participants
Holding on or letting go? Patient experiences of control, context, and care in oral esketamine treatment for treatment-resistant depression: A qualitative study. Patients with treatment-resistant depression participating in off-label oral esketamine... 2022 Qualitative study n = 17
Phenomenology and therapeutic potential of patient experiences during oral esketamine treatment for treatment-resistant depression: an interpretative phenomenological study. Patients with treatment-resistant depression undergoing oral esketamine treatment 2023 Qualitative study using Interpretative Phenomenological Analysis n = 17
Person-centred care during treatment with nasal esketamine - a qualitative study. Patients with treatment-resistant depression who had received at least eight treatments... 2025 Qualitative study n = 20
Esketamine Implementation Challenges in Psychiatry: A Qualitative Analysis of Mental Healthcare Providers’ Social Media Commentary Online posts and comments from mental healthcare providers 2026 Qualitative study n = 186
Integrative Use of Esketamine and Psychotherapy in a Real-World Outpatient Setting: A Mixed-Methods Case Series Adult patients with treatment-resistant depression receiving concurrent esketamine and... 2026 Qualitative study n = 5

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