ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol

Contemp Clin Trials. 2019 Feb;77:19-26. doi: 10.1016/j.cct.2018.12.009. Epub 2018 Dec 17.


Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3-5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies.

Trial registration: ClinicalTrials.gov NCT03113968.

Keywords: Clinical trial; Electroconvulsive therapy; Ketamine; Major depression; Non-inferiority; Treatment-resistant.

Publication types

  • Clinical Trial Protocol
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use
  • Cognition
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Depressive Disorder, Treatment-Resistant / therapy*
  • Electroconvulsive Therapy / adverse effects
  • Electroconvulsive Therapy / methods*
  • Equivalence Trials as Topic
  • Female
  • Humans
  • Ketamine / administration & dosage
  • Ketamine / adverse effects
  • Ketamine / therapeutic use*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Young Adult


  • Antidepressive Agents
  • Ketamine

Associated data

  • ClinicalTrials.gov/NCT03113968