Dissociation and Antidepressant Response to Subcutaneous Esketamine: A Clinical Study
K S de Freitas Goncalves, Vagner Deuel O de Tavares, Fernanda Palhano-Fontes, Patrícia Cavalcanti-Ribeiro, Victor Rocha Nobrega de Almeida, D. Barbosa, Tatiane Uetti Gomes Fernandes, Eduardo Igor Torquato Cardoso, Nicole Bezerra de Medeiros Lima, Aldielyson Jorge Cavalcante de Brito, Raynara Bolcont, Marcelo Falchi-Carvalho, Emerson Arcoverde Nunes, Dráulio Barros de Araújo, Nicole Leite Galvão‐coelho
Journal of Psychiatric Research July 1, 2026 DOI: 10.1016/j.jpsychires.2026.07.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary exploratory analysis Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Patients with treatment-resistant depression |
| Intervention | subcutaneous esketamine |
| Duration | Up to eight weekly doses |
| Topics | Depression Esketamine |
| Keywords | Depersonalization Beck depression inventory Derealization Antidepressant Dissociative disorders Dissociative experiences scale Psychological intervention Rating scale Clinical psychology Culprit Dissociation chemistry Depression economics Amnesia Anesthesia Clinical significance Clinical trial Exploratory research Electroconvulsive therapy studies |
| Key points | Responders exhibited significantly higher CADSS total scores and derealization scores compared with non-responders across the treatment period. |
Abstract
ABSTRACT: Introduction Ketamine and esketamine have reemerged as promising interventions for treatment-resistant depression (TRD), yet debate persists regarding the clinical relevance of acute dissociative experiences. This secondary exploratory analysis examined the relationship between dissociative experiences induced by subcutaneous esketamine and antidepressant response in patients with TRD, comparing responders and non-responders.
Methods: Patients received up to eight weekly subcutaneous doses of esketamine. Dissociation was assessed using the Clinician-Administered Dissociative States Scale (CADSS), and depressive symptoms were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory-II (BDI-II). Responders were defined as patients who achieved a ≥50% reduction in MADRS scores from baseline to the end of treatment, whereas participants who did not meet this criterion were classified as non-responders.
Results: Of 30 patients eligible for inclusion, 23 were included in the final analysis (mean age, 34.3 years; 65.2% women). Dissociation levels remained stable across treatment sessions. Responders exhibited significantly higher CADSS total scores (p = 0.024) and derealization scores (p = 0.011) compared with non-responders across the treatment period. Depersonalization and amnesia scores also tended to be higher among responders, although these differences did not reach statistical significance (p = 0.056 and p = 0.089, respectively). These exploratory findings suggest that dissociative experiences, particularly derealization, may represent clinically relevant correlates of antidepressant outcomes following subcutaneous esketamine treatment in TRD, although further prospective studies with larger samples and dose-controlled designs are needed before their clinical utility can be established.