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Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression

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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.
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.
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.
Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine’s antidepressant efficacy; the possibility of Type I errors in secondary analyses.
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.
Niciu, M. J., Shovestul, B. J., Jaso, B. A., Farmer, C., Luckenbaugh, D. A., Brutsche, N. E., … & Zarate, C. A. (2018). Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression. Journal of affective disorders232, 310-315. 10.1016/j.jad.2018.02.049
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