Depression with ECT Therapy Does Not Benefit From Ketamine

Ketamine does not appear to offer any benefits to patients who receive electroconvulsive therapy.

Ketamine does not appear to offer any benefits to patients who receive electroconvulsive therapy (ECT), according to new research published in the Lancet.

Preliminary research suggested that ketamine may reduce the memory impairment that may result from ECT, but findings have been inconsistent. Other prior studies suggested that participants receiving ketamine with ECT may experience longer seizures and increased agitation and confusion after waking up.

“Interpretation of the literature is made difficult by small sample sizes and differences in methods used by different groups,” the investigators noted.

In this randomized controlled trial, participants performed equally well on a verbal memory test whether they received ketamine or saline during their ECT treatments.

“The place of ketamine in combination with ECT has not been finally defined, but our study suggests that there is no beneficial effect when it is given at a standard dose of 0.5 mg during ECT as it is routinely given in the UK,” wrote Ian M. Anderson, MD, of the University of Manchester in the United Kingdom, and his colleagues.

The researchers recruited 79 adults with moderate or severe unipolar or bipolar depression at 11 sites throughout northern England. In the study, 40 participants were randomly assigned to receive 0.5 mg/kg of intravenous ketamine directly before anesthesia (propofol), and 39 participants received saline before anesthesia. Most participants had major depression with a recent severe episode that did not respond to approximately 4 medications. Of the 70 participants who completed the trial, 33 received ketamine and 37 received saline.

After 4 ECT treatments, the participants took a verbal recall test (HVLT-R-DR), which they repeated after the full course of ECT and at 1 and 4 months later. No significant differences in verbal test scores existed in the 2 groups at any point.

It took an average of 10 ECT treatments to reach remission in the patients receiving ketamine, compared to 7 in the saline group, but the difference was not significant. The difference in total adverse events, most commonly psychiatric events, between the groups — 45% in the ketamine group and 27% in the saline group — was also not significant. In the study, 2 patients in the ketamine group and 5 in the saline group experienced serious adverse events, including worsening depression, chest pain in 1 patient, and seizures in 1 patient.

“Some studies have suggested that ketamine could accelerate the clinical response to ECT, but we did not find any evidence for this,” the researchers wrote. “On average, participants treated with ketamine achieved remission later than those on saline, although this observation was not significant. However, the lower than predicted recruitment means that small- to-moderate sized benefits and moderate-to-large sized harms of ketamine cannot be excluded.”

The research was funded by the National Institute for Health Research. 


Anderson IM, Blamire A, Branton T, et al. Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial [published online March 27, 2017]. Lancet Psychiatry. doi:10.1016/S2215-0366(17)30077-9