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Clinical Trial
Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.
- Mark J Niciu, Bridget J Shovestul, Brittany A Jaso, Cristan Farmer, David A Luckenbaugh, Nancy E Brutsche, Lawrence T Park, Elizabeth D Ballard, and Carlos A Zarate.
- National Institutes of Health, National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Building 10/CRC, 10 Center Dr., Unit 7 Southeast, Room 7-5342, Bethesda, MD 20892, USA.
- J Affect Disord. 2018 May 1; 232: 310-315.
BackgroundKetamine 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.MethodsTreatment-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.ResultsFactor 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.LimitationsPossible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine's antidepressant efficacy; the possibility of Type I errors in secondary analyses.ConclusionsFrom 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.Published by Elsevier B.V.
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