Trial PaperAnxiety DisordersDepressive DisordersMajor Depressive Disorder (MDD)Safety & Risk ManagementEquity and EthicsKetamine

Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial

This randomised, double-blind, placebo-controlled study investigated the efficacy of using low-dose ketamine (35mg/70kg) as an anaesthetic adjunct to propofol during electroconvulsive therapy (ECT) for treating patients with depression (MDD). Adding ketamine did not alter the antidepressant efficacy or the hemodynamics of electroconvulsive therapy, although it may help reduce the dose requirements of propofol anaesthesia.

Authors

  • Woolsey, A. J.
  • Nanji, J. A.
  • Moreau, C.

Published

brazilian Journal of Psychiatry
individual Study

Abstract

Objective

Electroconvulsive therapy (ECT) is a well-established therapeutic intervention for major depressive disorder. Recent literature has shown that the anesthetic agent ketamine has some antidepressant properties at low doses and may be an alternative therapy for treatment-resistant major depressive disorder. We hypothesized that the use of low-dose ketamine as an anesthetic adjunct in ECT would more rapidly improve depression while maintaining hemodynamic stability than ECT with propofol alone.

Methods

Institutional ethics approval was obtained, and the use of ketamine in this study was approved by Health Canada. This is a randomized, double-blinded, placebo-controlled trial that involved ketamine administration at 0.5 mg/kg IV in addition to propofol anesthesia for ECT. The primary outcome was the number of ECT treatments required to achieve a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included the number of ECT treatments required to achieve a 25% reduction in MADRS score, as well as any differences in the Clinical Global Impression Scale for Severity, hemodynamic variables, and seizure duration. Adverse events were recorded for safety assessment.

Results

A total of 45 patients completed the study. No difference was found between groups with respect to the primary or secondary outcomes. The ketamine group showed a trend towards a decreased dose of propofol required to achieve adequate anesthesia. No adverse events were reported.

Conclusion

Low-dose ketamine does not improve psychiatric outcomes in the setting of propofol-based anesthesia for ECT. Specifically, ketamine did not reduce the number of ECT sessions necessary to achieve a 50 or 25% reduction in MADRS scores. Reassuringly, the fact that no differences in hemodynamic variables or unexpected adverse events occurred suggests that low-dose ketamine may be safely used in this setting should clinical indications warrant its use.

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Research Summary of 'Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial'

Introduction

Electroconvulsive therapy (ECT) is an established, highly effective treatment for major depressive disorder, with reported remission rates up to 87%, but its precise mechanism remains uncertain. Routine practice uses a short-acting general anaesthetic such as propofol to ensure patient comfort and safety; however, propofol is a potent antiepileptic that can shorten seizure duration, a factor that might reduce ECT efficacy. Ketamine, a dissociative anaesthetic with N-methyl-D-aspartate (NMDA) receptor antagonist properties, has shown rapid antidepressant effects at low, sub‑anaesthetic doses in outpatient settings and can prolong seizure duration when used as an induction agent, but higher doses are associated with haemodynamic and psychotomimetic effects. Woolsey and colleagues designed this trial to test whether adding low-dose intravenous ketamine to a propofol-based anaesthetic regimen for ECT would accelerate clinical improvement in depression compared with placebo. The primary hypothesis was that ketamine would reduce the number of ECT treatments required to achieve a 50% reduction in depressive symptoms as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS); secondary hypotheses addressed more modest symptom reductions, global severity, physiological parameters, seizure duration, and safety outcomes.

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