Adverse Events and Measurement of Dissociation After the First Dose of Esketamine in Patients With TRD
David Williamson, Ibrahim Turkoz, Ewa Wajs, Jaskaran Singh, Stephane Borentain, Wayne C. Drevets
The International Journal of Neuropsychopharmacology December 14, 2022 DOI: 10.1093/ijnp/pyac081 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of an open-label, long-term safety, phase 3 study Qualitative Peer reviewed |
|---|---|
| Sample size | 764 |
| Population | Patients with treatment-resistant depression |
| Intervention | Esketamine |
| Duration | Initial treatment session (40 minutes post first esketamine dose) |
| Topics | Esketamine |
| Keywords | Dissociative Dissociation chemistry Rating scale Adverse effect Psychosis Logistic regression Clinical psychology Developmental psychology Electroconvulsive therapy studies |
| Citations | 11 |
| Registration | NCT02497287 |
| Key points | CADSS scores and severity of dissociation adverse events generally move in the same direction, but with substantial variability, and psychotic symptoms were uncommon. |
Abstract
Background: "Dissociation" comprises distinct phenomena, some of which are associated with esketamine treatment and some may overlap with positive symptoms of psychosis. Relationships between dissociation and psychotic symptoms assessed by -clinician report vs conventional rating scales were investigated in a post hoc analysis of data from the initial treatment session in an -open-label, -long-term safety, phase 3 study of esketamine plus a newly initiated oral antidepressant in patients with treatment-resistant depression.
Methods: Adverse events of dissociation or psychosis were examined via investigator report and the Clinician Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale-Plus, respectively, 40 minutes post first esketamine dose. The range of CADSS total scores associated with investigator-reported severity of dissociation was determined by equipercentile linking. Logistic regression models and receiver operating curve analysis explored the CADSS cutoff point for determining presence/absence of dissociation. Frequency of response to specific CADSS items was examined to investigate qualitative differences in the pattern of symptoms reported across investigator-reported levels of adverse event severity.
Results: Dissociation was reported as an adverse event in 14.3% (109/764) of patients. Severity of most CADSS items increased with the severity of investigator-reported dissociation. No CADSS cutoff point discriminated well between the presence and absence of dissociation events. Hallucinations were reported as adverse events in 5 patients; none reported delusions.
Conclusions: CADSS scores and severity of dissociation adverse events move generally in the same direction; however, there is substantial variability in this relationship. No signature profile of dissociative experiences was revealed, and psychotic symptoms were uncommon.
Trial Registration: Clinical Trials.gov identifier: NCT02497287.
Comparable studies
Other non-randomized and open-label trials on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Adults with treatment-resistant depression | 2023 | Open-label, long-term extension study | n = 1,148 |
| Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Adults with treatment-resistant depression who participated in ≥1 of 6 phase 3 parent... | 2025 | Open-label, single-arm long-term extension study | n = 1,148 |
| Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Patients with treatment-resistant major depressive disorder and comorbid post-traumatic... | 2022 | Open-label, single-arm, retrospective pilot study | n = 11 |
| Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data Patients with treatment-resistant depression | 2020 | Post-hoc analysis of an open-label, long-term study | n = 778 |