Like Stepping Outside the Noise: Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression
Giada Versaci, Miriam Olivola, Kevin la Monica, Mauro Angeletti, V. Casati, Alice Frediani, Tiziano Prodi, Filippo Mazzoni, G. Miacca, Alessandro Guffanti, Natascia Brondino, V. Martiadis, Roberta Anniverno, Bernardo Dell'Osso
European Psychiatry June 1, 2026 DOI: 10.1192/j.eurpsy.2026.10616 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Qualitative study Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Patients with treatment-resistant depression treated with intranasal esketamine in Northern Italy |
| Intervention | Intranasal esketamine |
| Topics | Depression Esketamine |
| Key findings | Most patients described esketamine-induced dissociation as neutral to positive, interpreting it as peaceful, transformative, or a "pause" from suffering, while a minority reported transient fear or disorientation often eased by anticipatory guidance and post-session integration. The authors argue these states can function as a liminal mental state that temporarily interrupts maladaptive self-processing and may foster relief, insight, and psychological reorganization within a supportive therapeutic context. |
Abstract
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 states rather than adverse effects.
Methods: We conducted a qualitative, narrative-based study on 36 patients with treatment-resistant depression (TRD) treated with intranasal esketamine in Northern Italy (2022–2024). Patients provided detailed accounts of dissociative episodes during treatment. Narratives were anonymized and thematically analyzed, focusing on phenomenological dimensions: sensory alterations, temporal distortion, body–space reconfiguration, and emotional detachment from suffering.
Results: Four thematic domains emerged: 1. Sensory Intensification: Enhanced colors, synesthetic experiences, and altered auditory landscapes. 2. Temporal Distortion: Time dilation, loops, and present-centered awareness. 3. Body–Space Alteration: Weightlessness, out-of-body perspectives, and merging with surroundings. 4. Psychic Distance from Suffering: Temporary suspension of depressive thoughts and emotional pain. Most participants described neutral-to-positive experiences, interpreting dissociation as peaceful, transformative, or offering a “pause” from suffering. A minority reported transient fear or disorientation, often mitigated by anticipatory guidance and post-session integration. Image 1: Image 1: Long description.A conceptual diagram illustrating four psychological effects surrounding a central core of DISSOCIATION. See long description.
Conclusions: In TRD patients, esketamine-induced dissociation can function as a liminal mental state that temporarily interrupts maladaptive self-processing. When framed within a supportive therapeutic context, these states may foster relief, insight, and psychological reorganization. Clinical protocols should incorporate psychoeducation and post-treatment reflection to optimize meaning-making and reduce distress. Disclosure of Interest None Declared
Comparable studies
Other qualitative studies on esketamine for depression, 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 |
| Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study Adults with treatment-resistant depression receiving intranasal esketamine in... | 2026 | Qualitative exploratory study | n = 36 |
| 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 |