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

Carola Rong, Caroline Park, Joshua D Rosenblat, Mehala Subramaniapillai, Hannah Zuckerman, Dominika Fus, Yena L Lee, Zihang Pan, Elisa Brietzke, Rodrigo B Mansur, Danielle S Cha, Leanna M W Lui, Roger S McIntyre, Carola Rong, Caroline Park, Joshua D Rosenblat, Mehala Subramaniapillai, Hannah Zuckerman, Dominika Fus, Yena L Lee, Zihang Pan, Elisa Brietzke, Rodrigo B Mansur, Danielle S Cha, Leanna M W Lui, Roger S McIntyre

Abstract

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, ClinicalTrials.gov, 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.

Keywords: MDD; depression; ketamine; predictors; remission; response.

Conflict of interest statement

R.S.M. has received speaking fees from Allergan, AstraZeneca, Bristol-Meyers, Janssen-Ortho, Lundbeck, Otsuka, Purdue, Pfizer, Shire, Sunovion, Neurocrine and Takeda. The other authors report no potential conflict of interest.

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