Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression
This follow-up study (n=126) investigated whether the antidepressant effects of ketamine (35mg/70kg) were related to dissociative symptoms experienced by patients with (bipolar) depression, and found that the subjective effects of depersonalization were most closely related to the antidepressant response.
Authors
- Carlos Zarate
- Evan Ballard
- David Luckenbaugh
Published
Abstract
Background
Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters.
Methods
Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response.
Results
Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day 7) in one study. The amnesia subscale was unrelated to HAM-D percent change.
Limitations
Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine's antidepressant efficacy; the possibility of Type I errors in secondary analyses.
Conclusions
From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded.
Research Summary of 'Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression'
Introduction
Ketamine, an FDA-approved anaesthetic with dissociative effects at subanesthetic doses, produces rapid antidepressant effects in patients with major depressive disorder (MDD) and bipolar depression. Dissociation here refers to transient detachment from self or surroundings and can include depersonalization, derealization and amnesia; at typical clinical ketamine doses these phenomena are usually mild and short-lived. Prior studies have produced mixed findings about whether ketamine-induced dissociation is associated with antidepressant response: some small studies found no relationship, others found correlations with psychotomimetic symptoms, and an earlier report from the investigators observed that increased dissociative symptoms correlated with antidepressant improvement at 230 minutes and seven days post-infusion. These inconsistencies left unresolved whether specific dimensions of dissociation might uniquely predict clinical benefit. Niciu and colleagues designed the present follow-up study to test whether empirically derived subdimensions of the Clinician-Administered Dissociative States Scale (CADSS)—derealization, depersonalization, and amnesia—are differentially associated with subsequent antidepressant response to a single subanesthetic ketamine infusion. Using a larger pooled sample (n = 126) drawn from three clinical studies, the investigators hypothesised that greater dissociative symptoms would predict greater reductions in depressive symptoms and that particular CADSS subscales would show unique predictive relationships.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Niciu, M. J., Shovestul, B. J., Jaso, B. A., Farmer, C., Luckenbaugh, D. A., Brutsche, N. E., Park, L. T., Ballard, E. D., & Zarate, C. A. (2018). Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression. Journal of Affective Disorders, 232, 310-315. https://doi.org/10.1016/j.jad.2018.02.049
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