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Ketamine-based anesthesia improves electroconvulsive therapy outcomes: a randomized-controlled study

  • Jonathan J. Gamble
  • Henry Bi
  • Rudy Bowen
  • Grahme Weisgerber
  • Rohan Sanjanwala
  • Renuka Prasad
  • Lloyd Balbuena
Reports of Original Investigations

Abstract

Background

Major depressive disorder (MDD) is a common and debilitating condition that can be challenging to treat. Electroconvulsive therapy (ECT) is currently the therapeutic gold standard for treatment-resistant MDD. We tested our hypothesis that ketamine-based anesthesia for ECT results in superior improvement in treatment-resistant MDD outcomes compared with propofol-based anesthesia.

Methods

Patients with treatment-resistant MDD were enrolled in a randomized clinical trial with assignment to ketamine- or propofol-based anesthesia arms. Using a modified intention-to-treat analysis, we compared the median number of ECT treatments required to achieve a 50% reduction (primary outcome) and a score ≤ 10 (secondary outcome) on the Montgomery-Asberg depression rating scale (MADRS) between anesthesia groups.

Results

The study was terminated as significant results were found after the first planned interim analysis with 12 patients in each of the ketamine (intervention) and propofol (control) groups. All ketamine patients achieved at least a 50% MADRS reduction after a median of two ECT treatments whereas ten propofol patients (83%) achieved the same outcome after a median of four ECT treatments. All ketamine patients and seven propofol patients (58%) achieved MDD remission (MADRS 10). Log rank tests showed that both time-to-50% reduction and remission differed significantly between groups. Adverse events and recovery time were similar between groups.

Conclusions

In this early-terminated small-sized study, ketamine-based anesthesia compared with propofol-based anesthesia provided response and remission after fewer ECT sessions.

Trial registration

www.clinicaltrials.gov (NCT01935115). Registered 4 September 2013.

L’anesthésie à base de kétamine améliore les résultats de l’électro-convulsivothérapie : une étude randomisée contrôlée

Résumé

Contexte

Le trouble dépressif majeur (TDM) est une affection fréquente et invalidante qui peut être difficile à traiter. L’électro-convulsivothérapie (ECT) est actuellement l’option de choix pour les TDM résistant au traitement pharmacologique. Nous avons testé l’hypothèse qu’une anesthésie à base de kétamine pour l’ECT contribuerait à de meilleurs résultats dans le traitement du TDM résistant qu’une anesthésie à base de propofol.

Méthodes

Des patients atteints de TDM résistant au traitement ont été inclus dans cet essai clinique randomisé pour recevoir une anesthésie à base de kétamine ou une anesthésie à base de propofol. Nous avons comparé au moyen d’une analyse en intention-de-traiter modifiée le nombre médian d’ECT requis pour obtenir une réduction de 50% (critère d’évaluation principal) et un score ≤ 10 (critère d’évaluation secondaire) sur l’échelle d’évaluation de la dépression de Montgomery-Asberg (MADRS) entre les groupes d’anesthésies.

Résultats

L’étude a été arrêtée de façon précoce, car des résultats significatifs ont été trouvés à la première analyse intérimaire prévue avec 12 patients dans chaque groupe : kétamine (groupe interventionnel) et propofol (groupe témoin). Tous les patients du groupe kétamine ont obtenu une réduction d’au moins 50% sur l’échelle MADRS après un nombre médian de deux ECT, alors que seulement dix patients du groupe propofol (83%) parvenaient au même résultat après un nombre médian de 4 traitements par ECT. Tous les patients du groupe kétamine et sept patients du groupe propofol (58%) ont obtenu une rémission du TDM (MADRS ≤ 10). Des tests du rang logarithmique ont montré que le délai d’atteinte de la réduction de 50% et le délai d’obtention de la rémission étaient tous deux significativement différents entre les groupes. Les événements indésirables et les temps de récupération ont été semblables entre les deux groupes.

Conclusions

Dans cette étude de petite taille arrêtée précocement, l’anesthésie à base de kétamine a entraîné une réponse et une rémission après moins de séances d’ECT qu’une anesthésie à base de propofol.

Enregistrement de l’essai clinique

www.ClinicalTrials.gov (NCT01935115). Enregistré le 4 septembre 2013.

Notes

Acknowledgements

We gratefully acknowledge the assistance of Dr. Dennis Lawson and Dr Jennifer O’Brien of the University of Saskatchewan. We also acknowledge the Departments of Anesthesiology, Perioperative Medicine and Pain Management and Department of Psychiatry, University of Saskatchewan, in facilitating this study. Finally, we acknowledge the support of the Saskatoon Health Region and College of Medicine, University of Saskatchewan. Detailed information regarding estimation of sample size and individual Montgomery Asberg Depression Rating Scale scores are provided as Electronic Supplementary Material.

Conflicts of interest

Commercial or non-commercial affiliations that are or may be perceived to be a conflict of interest with the work for each author, and any other associations, such as consultancies: No author has any commercial or other affiliations that are, or may be perceived to be, a conflict of interest.

Editorial responsibility

This submission was handled by Dr. Gregory L. Bryson, Deputy Editor-in-Chief, Canadian Journal of Anesthesia.

Author contributions

The manuscript is the collaborative work of seven authors. Jonathan J. Gamble, Henry Bi, Rudy Bowen, Lloyd Balbuena, and Renuk Prasad conceptualized the study and provided theoretical guidance in interpretation. Rohan Sanjanwala, Henry Bi, and Grahme Weisgerber acquired the data. Lloyd Balbuena and Rohan Sanjanwala analyzed the data. Jonathan J. Gamble wrote the initial draft and all seven authors revised the manuscript. All of the authors approved the manuscript as submitted.

Funding

This study received support from the Schulman Research Award (University of Saskatchewan) and the Royal University Hospital Foundation (Saskatoon, Saskatchewan).

Supplementary material

12630_2018_1088_MOESM1_ESM.pdf (14 kb)
Supplementary material 1 (PDF 13 kb)
12630_2018_1088_MOESM2_ESM.pdf (53 kb)
Supplementary material 2 (PDF 52 kb)

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Copyright information

© Canadian Anesthesiologists' Society 2018

Authors and Affiliations

  1. 1.Department of Anesthesia, Perioperative Medicine, and Pain ManagementUniversity of Saskatchewan, Royal University HospitalSaskatoonCanada
  2. 2.Department of PsychiatryUniversity of Saskatchewan, Royal University HospitalSaskatoonCanada

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