학술논문
Adverse Events and Measurement of Dissociation After the First Dose of Esketamine in Patients With TRD
Regular Research Article
treatment-resistant depression
Regular Research Article
treatment-resistant depression
Document Type
Report
Author
Source
International Journal of Neuropsychopharmacology. March 2023, Vol. 26 Issue 3, p198, 9 p.
Subject
Language
English
ISSN
1461-1457
Abstract
INTRODUCTION Dissociation is a clinical construct that incorporates a variety of different types of symptoms, ranging from disturbances in perception of sensory, proprioceptive, or temporal information to disturbances in one's [...]
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 Keywords: esketamine, CADSS, dissociation, BPRS+, psychosis
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 Keywords: esketamine, CADSS, dissociation, BPRS+, psychosis