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

Hartej Gill, Barjot Gill, Nelson B Rodrigues, Orly Lipsitz, Joshua D. Rosenblat, Sabine El‐halabi, Flora Nasri, Rodrigo B. Mansur, Yena Lee, Roger S McIntyre

Neuroscience and Biobehavioral Reviews November 23, 2020 DOI: 10.1016/j.neubiorev.2020.11.020 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Population Patients with treatment-resistant depression
Intervention Ketamine
Dose 0.5 mg/kg
Topics Depression Esketamine Ketamine
Citations 92
Key findings A subanesthetic dose of IV ketamine does not worsen cognitive function and may improve working memory and visual learning in some patients with treatment-resistant depression.

Abstract

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 the 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.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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