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Open AccessArticle

Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, ON MT5 2S8, Canada
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
Department of Psychiatry, Federal University of São Paulo, São Paulo 05403-903, Brazil
Department of Pharmacology, University of Toronto, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2018, 15(4), 771;
Received: 28 February 2018 / Revised: 5 April 2018 / Accepted: 12 April 2018 / Published: 17 April 2018
(This article belongs to the Special Issue Adult Psychiatry )
Objectives: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. Method: Electronic search engines PubMed/MEDLINE,, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission. Results: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI), history of suicide, family history of alcohol use disorder), peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels), polysomnography (abnormalities in delta sleep ratio), neurochemistry (i.e., glutamine/glutamate ratio), neuroimaging (i.e., anterior cingulate cortex activity), genetic variation (i.e., Val66Met BDNF allele), and cognitive functioning (i.e., processing speed). High BMI and a positive family history of alcohol use disorder were the most replicated predictors. Conclusions: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information. View Full-Text
Keywords: ketamine; depression; MDD; response; predictors; remission ketamine; depression; MDD; response; predictors; remission
MDPI and ACS Style

Rong, C.; Park, C.; Rosenblat, J.D.; Subramaniapillai, M.; Zuckerman, H.; Fus, D.; Lee, Y.L.; Pan, Z.; Brietzke, E.; Mansur, R.B.; Cha, D.S.; Lui, L.M.W.; McIntyre, R.S. Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder. Int. J. Environ. Res. Public Health 2018, 15, 771.

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