Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis

J Psychiatr Res. 2022 Jul:151:693-709. doi: 10.1016/j.jpsychires.2022.04.037. Epub 2022 May 25.


Ketamine is a promising therapeutic option in treatment-resistant depression (TRD). The acute efficacy of ketamine in TRD has been demonstrated in replicated randomised-controlled trials (RCTs), but the generalizability of RCT data to real-world practice is limited. To this end, we conducted a systematic review (Search date: 25/12/2021; 1482 records identified) and meta-analysis of studies evaluating the real-world clinical effectiveness of ketamine in TRD patients. Four overlapping syntheses (Total n = 2665 patients; k = 79 studies) and 32 meta-regressions (Total n = 2050; k = 37) were conducted. All results suggest that the mean antidepressant effect is substantial (mean ± 95% CI, % responded = 45 ± 10%; p< 0.0001, % remitted = 30 ± 5.9%; p< 0.0001, Hedges g of symptomatological improvement = 1.44 ± 0.609; p < 0.0001), but the effect varies considerably among patients. The more treatment-resistant cases were found to remit less often (p < 0.01), but no such effect on response was evident (p > 0.05). Meta-regressions also confirmed that the therapeutic effect does not significantly decline with repeated treatments (p > 0.05). These results demonstrate that even the most treatment-resistant patients may benefit from ketamine, and that mid-to-long term treatment is effective in many patients.

Keywords: Bipolar disorder; Depression; Esketamine; Ketamine; Suicide; Treatment resistant depression.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Humans
  • Ketamine* / adverse effects
  • Treatment Outcome


  • Antidepressive Agents
  • Ketamine