Effect of ketamine dose on self-rated dissociation in patients with treatment refractory anxiety disorders

Ketamine produces dose-dependent dissociative symptoms in patients with treatment-resistant anxiety, while midazolam does not. The Clinician-Administered Dissociative States Scale (CADSS) shows high internal consistency (Cronbach alpha = 0.937) for measuring these symptoms, though it does not capture thought disorder. Individual items varied in their sensitivity to ketamine dose and magnitude of change. Removing items did not meaningfully improve the scale's reliability, and acceptable consistency remained even after excluding items unresponsive at lower doses. The CADSS is an internally consistent tool for assessing ketamine-induced dissociation in clinical trials for anxiety.

Study at a glance

Abstract

Patients receiving ketamine for refractory depression and anxiety report dissociative symptoms in the first 60 min post-dose. The most commonly used instrument to assess this is the Clinician-Administered Dissociative States Scale (CADSS), developed based on the assessment of patients with dissociative symptoms. Its psychometric properties for ketamine-induced dissociation have not been reported. We evaluated these from a study using 0.25–1 mg/kg ketamine and midazolam (as an active control) in 18 patients with treatment-resistant anxiety. Dissociation ratings were increased by ketamine in a dose-dependent manner. In contrast, midazolam showed no effect on ratings of dissociation. For individual CADSS items, the magnitude of change and the ketamine dose at which changes were observed were not homogenous. The Cronbach alpha for the total scale was high (0.937), with acceptable item-rest correlations for almost all individual items. Purposefully removing items to maximise alpha did not lead to meaningful improvements. Acceptable internal consistency was still observed after removing items which lacked evidence of responsiveness at lower doses. The high Cronbach alpha values identified in this study suggests that the CADSS is an internally consistent instrument for evaluating ketamine-induced dissociation in clinical trials in anxiety, although it does not capture symptoms such as thought disorder.