Anxiety DisordersMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersPTSDKetamine

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

This study (n=110) examined the psychometric properties of the CADSS, the instrument most commonly used to assess the acute psychoactive effects of ketamine, and found that it only partially captured those effects.

Authors

  • Gerard Sanacora
  • Scott Wilkinson

Published

Journal of Affective Disorders
individual Study

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.

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Research Summary of 'Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: analysis of the Clinician Administered Dissociative State Scale'

Introduction

Since 2000, randomized controlled trials have shown that subanesthetic doses of ketamine produce rapid antidepressant effects in unipolar and bipolar depression. At commonly used clinical doses (0.5 mg/kg IV over 40 minutes), ketamine also produces short-lived psychoactive effects—changes in perception and alertness—that typically resolve within an hour. These acute effects are often labelled "dissociative," and the Clinician Administered Dissociative State Scale (CADSS) has been the most widely used instrument to quantify them in ketamine research. However, the CADSS was developed and validated in other clinical contexts (notably PTSD) and, based on the authors' clinical and trial experience, may not fully capture the phenomenology elicited by subanesthetic ketamine in mood-disordered patients. Van Schalkwyk and colleagues set out to evaluate whether the CADSS adequately measures the acute psychoactive effects of intravenous ketamine and to identify aspects of the ketamine experience that the scale may miss. To address these aims they performed an exploratory factor analysis (EFA) of CADSS ratings obtained at the 40-minute infusion point from a pooled sample of 110 patients who received ketamine, and complemented the quantitative work with semi-structured qualitative interviews in a subsample to characterise first-person accounts of the acute experience. The mixed-methods approach was intended to show both where the CADSS aligns with patient experience and where it may require revision for ketamine research.

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Study Details

References (9)

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Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)

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Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)

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Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)

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Zanos, P., Moaddel, P. J., Morris, P. J. et al. · Nature (2016)

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