Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale

Abstract

Introduction: Ketamine has rapid-acting antidepressant effects. Frequently, ketamine administration also causes acute psychoactive effects – in trials, these effects are commonly measured using the Clinician Administered Dissociative State Scale (CADSS). However, the CADSS was not designed for this specific purpose, having been validated in other clinical contexts, and anecdotally does not appear to fully capture ketamine’s acute psychoactive effects. Methods: Data were obtained from 110 individuals with mood disorders (predominantly major depressive disorder) who underwent intravenous ketamine infusion. An exploratory factor analysis (EFA) was performed on the CADSS, along with assessment of internal consistency. Qualitative methods were used to conduct in-depth interviews with a subset of these participants to identify key features of the acute ketamine experience, including aspects that may not be captured by the CADSS. Results: The mean total score of the CADSS was low at 7.7 (SD 9.2). Analysis of internal consistency showed a Cronbach’s alpha of 0.74. Five CADSS items had low correlations with the total score. EFA lead to a one-factor solution containing 16 items. Five of the six highest loading items involved perceptual disturbances, either of time or sensation. Qualitative analyses of 10 patient narratives revealed two phenomena not captured on the CADSS: disinhibition and a sense of peace. Limitations: This study was by limited by the absence of other ratings of the participants’ experience. Conclusion: Findings suggest that the CADSS partially captures the acute effects of ketamine administration. Further research may seek to validate a revised version of the CADSS that more accurately measures these effects.

Analgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins

“…This contrasts with gabapentin and pregabalin, which do not notably cause dissociative effects, disrupt memory nor cause agitation or psychosis in clinical use. Although ketamine (the most widely studied NMDA antagonist for treating pain) is used primarily for perisurgical pain (Kreutzwiser and Tawfic, 2019) and increasingly for treatment-resistant depression (Murrough et al, 2013;van Schalkwyk et al, 2018), it is not used for chronic neuropathic pain (Gilron, 2007), and it has strong psychotomimetic properties (Sos et al, 2013).…”

The Altered-State-of-Consciousness Aspect of a Feeling of Lightness Is Reported to Be Associated with Antidepressant Benefits by Depressed Individuals Receiving Ketamine Infusions: A Systematic Analysis of Internet Video Testimonials

“…There are two frequent effects of ketamine whose potential interrelationship has hardly been investigated: a feeling of lightness/floating in healthy participants and recreational users [1-3], and temporary antidepressant benefits in individuals with treatment-refractory depression [4, 5]. Feelings of lightness/floating are a typical occurrence in psychoactive-substance- or psychologically induced altered states of consciousness [6, 7].…”

Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence

“…There is an inverse relationship between ketamine metabolites and CADSS scores, which may also contribute to sex differences in disassociation symptoms severity [27]. Importantly, the validity of the CADSS for IV ketamine has been criticized as there is no robust association between dissociation symptoms and antidepressive response [28,29]. A systematic review of 60 studies reported that headaches, dizziness, dissociation, and elevated blood pressure were the most frequently reported adverse events of IV ketamine [9].…”

“…We used the CADSS as the primary safety instrument to quantify the severity of dissociation. The CADSS was not developed primarily as a safety measure for ketamine treatment and likely underestimates the extent of dissociation experience with ketamine [29]. It should also be recognized that the CADSS was initially developed for dissociative symptoms of PTSD and may not adequately capture the phenomenology of IV ketamine treatment for TRD.…”