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.


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.”

Authors: Mark J. Niciu, Bridget J. Shovestul, Brittany A. Jaso, Cristan Farmer, David A. Luckenbaugh, Nancy E. Brutsche, Lawrence T. Park, Elizabeth D. Ballard & Carlos A. Zarate Jr.

Study details

Compounds studied

Topics studied
Depression Treatment-Resistant Depression Bipolar Disorder

Study characteristics



Authors associated with this publication with profiles on Blossom

Mark Niciu
Mark Niciu is an Assistant Professor of Psychiatry at the University of Iowa. Mark and his team are interested in the therapeutic effects of ketamine.