DOI: 10.1192/j.eurpsy.2026.10616 ISSN: 0924-9338

Like Stepping Outside the Noise: Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression

G. Versaci, M. Olivola, K. La Monica, M. C. Angeletti, V. Casati, A. Frediani, T. Prodi, F. Mazzoni, G. Miacca, A. Guffanti, N. Brondino, V. Martiadis, R. Anniverno, B. M. Dell’osso

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.

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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

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