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

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.