Trial PaperAnxiety DisordersDepressive DisordersAdolescentsTreatment-Resistant Depression (TRD)Neurocognitive DisordersKetamine

Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression

This randomised, double-blind, active placebo-controlled study (n=90) compared the antidepressant efficacy between ketamine (56mg/70kg), the anesthetic propofol (56mg/70kg), and the combination of ketamine (35mg/70kg) plus propofol (35mg/70kg), within the context of pretreatment for electroconvulsive therapy for patients with treatment-resistant depression (TRD). Compared to the others, the ketamine group exhibited earlier improvements in depression, better seizure parameters and seizure quality in electroconvulsive therapy, and a lower degree of executive cognitive impairment, which highlights the usefulness of ketamine-assisted electroconvulsive therapy for treating depression.

Authors

  • Zhong, X.
  • He, H.
  • Zhang, C.

Published

Journal of Affective Disorders
individual Study

Abstract

Background

Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects.

Methods

Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters.

Results

The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group.

Limitations

The postoperative dissociative side effect was not assessed.

Conclusions

Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD.

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Research Summary of 'Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression'

Introduction

Zhong and colleagues situate the study within the clinical problem of treatment-resistant depression (TRD), noting that a substantial minority of patients fail to remit after adequate trials of antidepressant drugs. Electroconvulsive therapy (ECT) is presented as an effective option for TRD, but response rates when common anaesthetic agents (for example propofol, thiopental or etomidate) are used are only around 50–60%, motivating investigation of augmentation strategies. Ketamine, an NMDA receptor antagonist with rapid antidepressant effects at low intravenous doses, has been proposed as an anaesthetic agent for ECT to improve antidepressant outcomes and possibly protect cognition, but prior ECT studies have produced inconsistent results and suggested a possible dose–response relationship for ketamine's mood effects. This study set out to compare three anaesthetic approaches for ECT in TRD: an anaesthetic dose of ketamine, a subanaesthetic ketamine plus propofol combination, and propofol alone. The investigators aimed to evaluate effects on depressive symptoms, seizure parameters during ECT, neurocognitive outcomes, and safety, with particular interest in whether anaesthetic versus subanaesthetic ketamine produces different antidepressant and cognitive effects.

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Study Details

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References (2)

Papers cited by this study that are also in Blossom

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)

The role of ketamine in treatment-resistant depression: a systematic review

Serafini, G., Howland, R. H., Rovedi, F. et al. · Current Neuropharmacology (2014)

Cited By (1)

Papers in Blossom that reference this study

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

Woolsey, A. J., Nanji, J. A., Moreau, C. et al. · brazilian Journal of Psychiatry (2022)

7 cited

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