Article Text

Download PDFPDF

Effects of ketamine in electroconvulsive therapy for major depressive disorder: meta-analysis of randomised controlled trials
  1. Xiao-Mei Li1,
  2. Zhan-Ming Shi2,
  3. Pei-Jia Wang1 and
  4. Hua Hu1
  1. 1Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  2. 2Department of Psychiatry, Chongqing Jiangbei Mental Health Center, Chongqing, China
  1. Correspondence to Dr Hua Hu; huhuateam{at}


Background The use of ketamine in electroconvulsive therapy (ECT) has been examined in the treatment of major depressive disorder (MDD); however, there has been no systematic review and meta-analysis of related randomised controlled trials (RCTs).

Aim To examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.

Methods Two reviewers searched Chinese (China National Knowledge Infrastructure and Wanfang) and English (PubMed, PsycINFO, Embase and Cochrane Library) databases from their inception to 23 July 2019. The included studies' bias risk was evaluated using the Cochrane risk of bias assessment tool. The primary outcome of this meta-analysis was improved depressive symptoms at day 1 after a single ECT treatment session. Data were pooled to calculate the standardised mean difference and risk ratio with their 95% CIs using RevMan V.5.3. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the whole quality of evidence.

Results Four RCTs (n = 239) compared ketamine alone or ketamine plus propofol (n = 149) versus propofol alone (n = 90) in patients with MDD who underwent a single ECT session. Three RCTs were considered as unclear risk with respect to random sequence generation using the Cochrane risk of bias. Compared with propofol alone, ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms at days 1, 3 and 7 after a single ECT session. Moreover, compared with propofol alone, ketamine alone and the combination of ketamine and propofol were significantly associated with increased seizure duration and seizure energy index. Compared with propofol, ketamine alone was significantly associated with increased opening-eye time. Based on the GRADE approach, the evidence level of primary and secondary outcomes ranged from very low (26.7%, 4/15) to ‘low’ (73.3%, 11/15).

Conclusion Compared with propofol, there were very low or low evidence levels showing that ketamine alone and the combination of ketamine and propofol appeared to rapidly improve depressive symptoms of patients with MDD undergoing a single ECT session. There is a need for high-quality RCTs.

  • ketamine
  • propofol
  • electroconvulsive therapy

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors X-ML and Z-MS selected the studies, conducted the statistical analysis, extracted the data and wrote the first draft. HH reviewed all the data and helped mediate disagreements. HH and P-JW made critical revisions. All the authors contributed to the interpretation of data and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No additional unpublished data are sharing.