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; Carlos A Zarate

doi:10.1016/j.jad.2018.02.049

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

Journal article

Peer reviewed

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

Journal of affective disorders, Vol.232, pp.310-315

05/2018

DOI: 10.1016/j.jad.2018.02.049

PMCID: PMC5858990

PMID: 29501990

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Abstract

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. •Intra-infusion dissociation is associated with antidepressant response to ketamine.•Antidepressant response may be uniquely related to dissociative symptom clusters.•Depersonalization was globally associated with antidepressant response.•Derealization was discriminately associated with antidepressant response.

Depression

Ketamine

Dissociation

Details

Title: Subtitle: Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression
Creators: Mark J Niciu - 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
Bridget J Shovestul - 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
Brittany A Jaso - University of Miami, Department of Psychology, P.O. Box 248185-0751, Coral Gables, FL 33124-0751, USA
Cristan Farmer - 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
David A Luckenbaugh - National Institutes of Health, Office of Equity, Diversity and Inclusion, 2115 E Jefferson St., Rockville, MD 20892, USA
Nancy E Brutsche - 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
Lawrence T Park - 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
Elizabeth D Ballard - 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
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
Resource Type: Journal article
Publication Details: Journal of affective disorders, Vol.232, pp.310-315
DOI: 10.1016/j.jad.2018.02.049
PMID: 29501990
PMCID: PMC5858990
NLM abbreviation: J Affect Disord
ISSN: 0165-0327
eISSN: 1573-2517
Publisher: Elsevier B.V
Grant note: name: Intramural Research Program at the National Institute of Mental Health, National Institutes of Health, award: (IRP-NIMH-NIH, ZIA MH002857, NIH Protocol 04-M-0222
Language: English
Date published: 05/2018
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003462602771

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