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The evidence for ketamine treatment in older adults with psychiatric illness: a scoping review

Kayla Murphy, Julia C. Golden, Haley Schuster, Rajesh R. Tampi

Therapeutic Advances in Chronic Disease October 1, 2025 DOI: 10.1177/20406223251384803 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Peer reviewed
Population Older adults (age >60) with psychiatric disorders
Intervention Ketamine
Topics Depression Ketamine Esketamine
Keywords Depression economics Delirium Medline Schizophrenia object-oriented programming Epidemiology Clinical psychology
Citations 3
Key findings Ketamine shows mixed results for depression and delirium in older adults, with some studies showing improvement and others showing no benefit or harm, and data are lacking for other psychiatric conditions.

Abstract

Background: Ketamine, an N-methyl-D-aspartate antagonist, has been used for decades as an anesthetic agent, but more recently it has been studied in psychiatric illness. Though ketamine has been investigated for use in the general population, fewer studies have investigated the efficacy and tolerability of this treatment for older (age >60) adults.

Objectives: This review sought to compile the randomized controlled trials (RCTs) investigating the evidence for ketamine treatment in older adults with psychiatric disorders. Eligibility criteria: Only RCTs published in English language journals, or with official English language translations, and human studies were included. Sources of evidence: Our team searched PubMed, Cochrane Database, and Ovid with the terms ketamine, depression, suicidal ideation, bipolar disorder, mania, anxiety, schizophrenia, psychotic disorders, dementia, delirium, and post-traumatic stress disorder. Charting

Methods: Covidence was used to extract and organize included studies.

Results: Our review yielded 14 RCTs and 2 post-hoc analyses evaluating ketamine treatment in older patients. Eight of these studies examined ketamine for the treatment of delirium, while the remaining eight examined its use in depression. The studies had significant heterogeneity so direct comparisons of the results were challenging. However, five studies showed no significant impact of ketamine on delirium incidence. Two studies showed a lower incidence of delirium in the ketamine group, but another study showed a higher incidence of delirium with ketamine. Four studies showed improvement in depressive symptoms with ketamine treatment, while the others showed a lack of improvement. Most reported side effects were mild.

Conclusion: Several studies have investigated ketamine for depression and delirium in older adults and show mixed results. This review reveals the paucity of current data on ketamine for other psychiatric conditions in older adults. It reaffirms that use of ketamine in older adults with psychiatric illness, including depression and delirium, remains an individual risk versus benefit analysis using shared decision making.

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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