Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial

The Lancet Psychiatry
27 March 2017

Prof Ian M Anderson, MD, Prof Andrew Blamire, PhD, Tim Branton, MBBS, Ross Clark, MBChB, Darragh Downey, PhD, Prof Graham Dunn, PhD, Andrew Easton, MMedSc, Prof Rebecca Elliott, PhD, Prof Clare Elwell, PhD, Katherine Hayden, MBChB, Fiona Holland, MSc, Salman Karim, MD, Prof Colleen Loo, MD, Jo Lowe, Rajesh Nair, MBBS, Timothy Oakley, MBChB, Antony Prakash, MBBS, Parveen K Sharma, MD, Prof Stephen R Williams, DPhil, R Hamish McAllister-Williams, MD on behalf of the Ketamine-ECT Study team



The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine.


In this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study. Patients were randomly assigned (1:1) to ketamine (0·5 mg/kg intravenous bolus) or saline adjunctive to the anaesthetic for the duration of their ECT course. Patients and assessment and ECT treatment teams were masked to treatment allocation, although anaesthetists administering the study medication were not. We analysed the primary outcome, Hopkins Verbal Learning Test-Revised delayed verbal recall (HVLT-R-DR) after four ECT treatments, using a Gaussian repeated measures model in all patients receiving the first ECT treatment. In the same population, safety was assessed by adverse effect monitoring. This trial was registered with International Standard Randomised Controlled Trial Number, number ISRCTN14689382.


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