A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019

J Affect Disord. 2020 Dec 1:277:831-841. doi: 10.1016/j.jad.2020.09.007. Epub 2020 Sep 7.


Background: Sub-anaesthetic administration of ketamine is an emerging practice in patients presenting treatment resistant depression (TRD), however several outstanding questions have yet to be answered.

Objective: To evaluate the effect of intravenous ketamine infusion for patients presenting TRD on depression scores, clinical remission and response rates, and to assess its efficacy over both time and frequency.

Methods: Five databases were searched up to January 4th 2019 to include primary studies evaluating the use of sub-anaesthetic dose of ketamine in adults presenting TRD. Two reviewers independently performed the study selection, quality assessment and data extraction. Results were summarised in a narrative synthesis. A meta-analysis using a random effects model was performed when possible to examine changes in standardized mean differences and odds ratios of outcome measures at 4 hours, 24 hours, or 7 days post-infusion.

Results: Twenty-eight studies in 35 publications were included. A strong ketamine effect was observed within 4 hours following a single infusion, and peaked at 24 hours. Ketamine's effectiveness was still present, yet somewhat diminished, 7 days post-infusion. Multiple infusions resulted in an enhanced and prolonged ketamine effect.

Limits: Due to insufficient data, long-term safety and efficacy of ketamine utilisation in patients presenting TRD are yet to be investigated.

Conclusions: Results provide support for the use of ketamine in the rapid management of depressive symptoms. While ketamine appears promising in the short-term treatment of TRD, more clinical and experimental data is needed with regards to the efficacy, tolerance and security of long-term administration of ketamine.

Keywords: Intravenous Ketamine; Meta-analysis; Systematic review; Treatment resistant depression.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Humans
  • Infusions, Intravenous
  • Ketamine* / adverse effects


  • Ketamine