Trial PaperDepressive DisordersMajor Depressive Disorder (MDD)Neuroimaging & Brain MeasuresKetamine

Predictive value of heart rate in treatment of major depression with ketamine in two controlled trials

This open-label study (n=51) found that a large increase in heart rate (HR) and -variability (HRV) predicted better outcomes for those suffering from depression (MDD) after administration of ketamine.

Authors

  • Erich Seifritz
  • Martin Brunovský
  • Jiří Horacek

Published

Clinical Neurophysiology
individual Study

Abstract

Objective

Ketamine has been shown to be effective in treatment of episodes of major depressive disorder (MDD). This controlled study aimed to analyse the predictive and discriminative power of heart rate (HR) and heart rate variability (HRV) for ketamine treatment in MDD.

Methods

In 51 patients, HR and HRV were assessed at baseline before and during ketamine infusion and 24 hours post ketamine infusion. Montgomery-Åsberg Depression Rating Scale (MADRS) was used to assess changes of depressive symptoms. A 30% or 50% reduction of symptoms after 24 hours or within 7 days was defined as response. A linear mixed model was used for analysis.

Results

Ketamine infusion increased HR and HRV power during and after infusion. Responders to ketamine showed a higher HR during the whole course of investigation, including at baseline with medium effect sizes (Cohen’s d = 0.47-0.67). Furthermore, HR and HRV power discriminated between responders and non-responders, while normalized low and high frequencies did not.

Conclusion

The findings show a predictive value of HR and HRV power for ketamine treatment. This further underlines the importance of the autonomous nervous system (ANS) and its possible malfunctions in MDD.

Significance

The predictive power of HR and HRV markers should be studied in prospective studies. Neurophysiological markers could improve treatment for MDD via optimizing the choice of treatments.

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Research Summary of 'Predictive value of heart rate in treatment of major depression with ketamine in two controlled trials'

Introduction

Meyer and colleagues frame the study against a background in which ketamine has shown rapid antidepressant effects, but objective predictors of which patients will benefit remain scarce. Previous work has explored genetic markers (for example BDNF polymorphisms), functional neuroimaging correlates, MRS glutamate metrics and sleep-architecture features as candidate predictors, yet clinical implementation has been limited. The authors note that ketamine exerts marked effects on the autonomic nervous system (ANS), typically increasing heart rate (HR) via sympathetic activation, and highlight prior literature linking reduced heart rate variability (HRV) to depression severity and to differential antidepressant response, suggesting that ANS measures could carry predictive information. This study set out to evaluate whether HR and HRV-derived parameters, measured before, during and after a single intravenous ketamine infusion, discriminate responders from non-responders in major depressive disorder (MDD). The principal aim was to test the predictive and discriminative power of simple ECG-derived markers for ketamine treatment outcome, with the hypothesis that higher baseline sympathetic tone (higher HR, greater HRV power and increased low-frequency power) would be associated with larger symptomatic improvement after ketamine.

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Study Details

Related Clinical Trial

Completed

Ketamine Autonomic / EEG Biomarkers in MDD: Pooled Czech Controlled Trials 2010–2015 (Meyer / Horacek / Novak, NIMH CZ)

Pooled secondary analysis of two Czech unregistered controlled ketamine infusion studies conducted 2010–2015 (Clin Neurophysiol 2021; Meyer T, Brunovsky M, Horacek J, Novak T, Andrashko V; National Institute of Mental Health / Charles University, Czech Republic; PMID 33888426). Total n=51 MDD inpatients across two studies; racemic IV ketamine 0.54 mg/kg administered over 30 min. Primary focus: autonomic nervous system responses (heart rate variability, sympatho-vagal balance) as predictors/mediators of antidepressant effect; EEG biomarkers also assessed. Study periods pooled: approximately 2010–2015 across two Prague-based sites. No CT.gov registration; no registration number reported in methods. CT.gov PMID reverse-lookup: 0 hits.

Started
Type
interventional
Randomized
No
Registry ID
HORACEK-NOVAK-2010-2015-CLINNEURO-KETAMINE-MDD-CZECH

References (2)

Papers cited by this study that are also in Blossom

Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies

Han, Y., Chen, J., Zou, D. et al. · Neuropsychiatric Disease And Treatment (2016)

A consensus statement on the use of ketamine in the treatment of mood disorders

Sanacora, G., Frye, M. A., McDonald, W. et al. · JAMA Psychiatry (2017)

470 cited

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Predictive value of heart rate in treatment of... — Research Summary & Context | Blossom