Do the dissociative side effects of ketamine mediate its antidepressant effects?

David A Luckenbaugh; Mark J Niciu; Dawn F Ionescu; Neal M Nolan; Erica M Richards; Nancy E Brutsche; Sara Guevara; Carlos A Zarate

doi:10.1016/j.jad.2014.02.017

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Do the dissociative side effects of ketamine mediate its antidepressant effects?

Journal article

Peer reviewed

Do the dissociative side effects of ketamine mediate its antidepressant effects?

David A Luckenbaugh, Mark J Niciu, Dawn F Ionescu, Neal M Nolan, Erica M Richards, Nancy E Brutsche, Sara Guevara and Carlos A Zarate

Journal of affective disorders, Vol.159, pp.56-61

04/2014

DOI: 10.1016/j.jad.2014.02.017

PMCID: PMC4065787

PMID: 24679390

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Abstract

The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression. Psychotomimetic symptoms, dissociation and hemodynamic changes are known side effects of ketamine, but it is unclear if these side effects relate to its antidepressant efficacy. Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item Hamilton Depression Rating scale (HDRS) at 40 and 230min and Days 1 and 7. Pearson correlations showed significant association between increased CADSS score at 40min and percent improvement with ketamine in HDRS at 230min (r=-0.35, p=0.007) and Day 7 (r=-0.41, p=0.01). Changes in YMRS or BPRS Positive Symptom score at 40min were not significantly correlated with percent HDRS improvement at any time point with ketamine. Changes in systolic blood pressure, diastolic blood pressure, and pulse were also not significantly related to HDRS change. Secondary data analysis, combined diagnostic groups, potential unblinding. Among the examined mediators of ketamine׳s antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant. Prospective, mechanistic investigations are critically needed to understand why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine.

Prospective Studies

Humans

Middle Aged

Male

Treatment Outcome

Bipolar Disorder - drug therapy

Bipolar Disorder - psychology

Antidepressive Agents - therapeutic use

Depressive Disorder, Major - psychology

Dissociative Disorders - chemically induced

Ketamine - adverse effects

Psychiatric Status Rating Scales

Adult

Female

Ketamine - therapeutic use

Antidepressive Agents - adverse effects

Depressive Disorder, Major - drug therapy

Details

Title: Subtitle: Do the dissociative side effects of ketamine mediate its antidepressant effects?
Creators: David A Luckenbaugh - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Mark J Niciu - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Dawn F Ionescu - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Neal M Nolan - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Erica M Richards - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Nancy E Brutsche - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Sara Guevara - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA
Carlos A Zarate - Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD USA. Electronic address: zaratec@mail.nih.gov
Resource Type: Journal article
Publication Details: Journal of affective disorders, Vol.159, pp.56-61
DOI: 10.1016/j.jad.2014.02.017
PMID: 24679390
PMCID: PMC4065787
NLM abbreviation: J Affect Disord
ISSN: 0165-0327
eISSN: 1573-2517
Publisher: Netherlands
Grant note: ZIA MH002927-03 / Intramural NIH HHS ZIA MH002857-09 / Intramural NIH HHS
Language: English
Date published: 04/2014
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003489202771

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