The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research

Neurosci Biobehav Rev. 2021 Jan;120:78-85. doi: 10.1016/j.neubiorev.2020.11.020. Epub 2020 Nov 23.


Replicated evidence has documented cognitive deficits in populations with treatment-resistant depression (TRD). Approximately 40 % of patients with MDD present with impairment of one or more cognitive domains. As such, there is an unmet need to discover treatments that have pro-cognitive effects in TRD patients. Ketamine has demonstrated efficacy as a rapid-onset intervention for the treatment of depression. The objective of the current review was to assess the effects of ketamine on cognition in TRD patients. We systematically searched PubMed, Google Scholar and PsycINFO between database inception to March 24th, 2020. We identified five studies that evaluated cognition in TRD populations following ketamine treatment. All studies included a 0.5 mg/kg subanesthetic intravenous (IV) administration of ketamine. One study found significant improvements in complex (p = .008) and simple (p = .027) working memory and one study found improvements in visual learning memory following IV ketamine infusions (p = .014). Improvements in speed of processing and verbal learning memory were observed in anxious TRD participants only. Importantly, a subanesthetic dose of IV ketamine does not worsen cognitive function.

Keywords: Esketamine; Major depression; Neurocognition; Racemic ketamine; Treatment-resistant depression.

Publication types

  • Review
  • Systematic Review

MeSH terms

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


  • Antidepressive Agents
  • Ketamine