Dissociation and Antidepressant Response to Subcutaneous Esketamine: A Clinical Study

In patients with treatment-resistant depression receiving up to eight weekly subcutaneous doses of esketamine, those who responded to treatment (≥50% reduction in MADRS scores) showed significantly higher levels of dissociation, particularly derealization, compared with non-responders. Depersonalization and amnesia scores also tended to be higher among responders, though these differences were not statistically significant. The authors suggest that dissociative experiences, especially derealization, may be clinically relevant correlates of antidepressant outcomes, but note that further prospective studies with larger samples and dose-controlled designs are needed before clinical utility can be established.

Study at a glance

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.