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The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder

Mark J. Niciu, Nicolas D. Iadarola, Dipavo Banerjee, David A. Luckenbaugh, Minkyung Park, Marc S. Lener, Lawrence T. Park, Dawn F. Ionescu, Elizabeth D. Ballard, Nancy E. Brutsché, Nirmala Akula, Francis J. McMahon, Rodrigo Machado‐Vieira, Allison C. Nugent, Carlos A. Zarate

Journal of Psychopharmacology October 17, 2017 DOI: 10.1177/0269881117732514 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 55
Population Unmedicated individuals with treatment-resistant major depressive disorder
Intervention Ketamine infusion
Dose 0.5 mg/kg
Duration Single 40-minute infusion with follow-up at 230 minutes, 1 day, and 1 week
Topics Depression Ketamine Esketamine
Keywords Antidepressant Anesthesia Hippocampus Amygdala
Citations 23
Key findings Baseline subcortical volumes did not correlate with ketamine's antidepressant efficacy, but thalamic volume and BDNF genotype may together predict rapid response.

Abstract

Background: This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype.

Methods: Unmedicated subjects with treatment-resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software. The amygdala, hippocampus, and thalamus were selected a priori for analysis. All subjects received a single 0.5mg/kg × 40-minute ketamine infusion. Pearson correlations were performed with subcortical volumes and percent change in MADRS score (from baseline to 230 minutes, 1 day, and 1 week post-infusion).

Results: Raw and corrected subcortical volumes did not correlate with antidepressant response at any timepoint. In val/val subjects ( n=23), corrected left and right thalamic volume positively correlated with antidepressant response to ketamine at 230 minutes post-infusion but did not reach statistical significance. In met carriers ( n=14), corrected left and right thalamic volume negatively correlated with antidepressant response to ketamine.

Conclusion: Baseline subcortical volumes implicated in MDD did not correlate with ketamine's antidepressant efficacy. Baseline thalamic volume and BDNF genotype may be a combinatorial rapid antidepressant response biomarker.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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