A systematic review and meta-analysis of randomized controlled trials of adjunctive ketamine in electroconvulsive therapy: Efficacy and tolerability

Alexander McGirr, Marcelo T. Berlim, David J. Bond, Nicholas H. Neufeld, Peter Y. Chan, Lakshmi N. Yatham, Raymond W. Lam

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations


Background: Electroconvulsive therapy (ECT) remains one of the most effective tools in the psychiatric treatment armamentarium, particularly for refractory depression. Yet, there remains a subset of patients who do not respond to ECT or for whom clinically adequate seizures cannot be elicited, for whom ketamine has emerged as a putative augmentation agent. Methods: We searched EMBASE, PsycINFO, CENTRAL, and MEDLINE from 1962 to April 2014 to identify randomized controlled trials evaluating ketamine in ECT (PROSPERO #CRD42014009035). Clinical remission, response, and change in depressive symptom scores were extracted by two independent raters. Adverse events were recorded. Drop-outs were assessed as a proxy for acceptability. Meta-analyses employed a random effects model. Results: Data were synthesized from 5 RCTs, representing a total of 182 patients with major depressive episodes (n=165 Major Depressive Disorder, n=17 Bipolar Disorder). ECT with ketamine augmentation was not associated with higher rates of clinical remission (Risk Difference (RD) = 0.00; 95%CI = -0.08 to 0.10), response (RD = -0.01; 95%CI = -0.11 to 0.08), or improvements in depressive symptoms (SMD = 0.38; 95%CI = -0.41 to 1.17). Ketamine augmentation was associated with higher rates of confusion/disorientation/prolonged delirium (OR=6.59, 95%CI: 1.28-33.82, NNH=3), but not agitation, hypertension or affective switches. Conclusion: Our meta-analysis of randomized controlled trials of ketamine augmentation in the ECT setting suggests a lack of clinical efficacy, and an increased likelihood of confusion. Individuals for whom adequate seizures or therapeutic response cannot be obtained have not been studied using randomized controlled designs. Additional research is required to address the role of ketamine in this population.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalJournal of Psychiatric Research
StatePublished - Mar 1 2015

Bibliographical note

Funding Information:
LNY has received research grants from or is on speaker/advisory boards for AstraZeneca, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Eli Lilly & Co., GlaxoSmithKline, Janssen, Michael Smith Foundation for Health Research, Novartis, Pfizer, Ranbaxy, Servier, and the Stanley Foundation.

Funding Information:
DJB has received speaking fees or acted as a consultant for: the Canadian Network for Mood and Anxiety Treatments (CANMAT), the Canadian Psychiatric Association, Pfizer, Sunovion, BMS, Otsuka, Astra-Zeneca, Janssen-Ortho and Myriad; and has received research support from: the Canadian Institutes of Health Research (CIHR), the UBC Institute of Mental Health/Coast Capital Depression Research Fund, and Pfizer.

Publisher Copyright:
© 2015 Elsevier Ltd.


  • ECT
  • Electroconvulsive therapy
  • Ketamine
  • Ketofol
  • Major depression


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