Ketamine and Esketamine for Late-Life Depression: A Systematic Review of Efficacy, Safety, and Tolerability.
Ronesh Sukhdeo, Jocelyn K. Tamura, Christine E. Dri, Roger S McIntyre
The American journal of geriatric psychiatry August 1, 2025 DOI: 10.1016/j.jagp.2025.08.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Open-label Peer reviewed |
|---|---|
| Sample size | 757 |
| Population | Adults aged 60 years and older with major depression |
| Interventions | Ketamine ketamine combined with ECT |
| Topics | Depression Esketamine Ketamine |
| Key findings | Across 13 prospective trials (757 adults aged 60+), antidepressant effects of ketamine were mixed: some studies showed symptomatic improvement, but not all reported positive outcomes. Adverse events were generally mild to moderate and rarely led to discontinuation, and cognitive outcomes were mostly stable or improved, with small long-term declines in reaction time. Ketamine used as an ECT anesthetic did not enhance antidepressant outcomes. The authors rate evidence certainty as very low to low. |
Abstract
Ketamine has emerged as a promising treatment for major depression, though its efficacy and safety remain incompletely characterized in older adults. This systematic review synthesizes current evidence for ketamine in geriatric depression. A search of PubMed, EMBASE, and PsycINFO was conducted. Prospective clinical trials were included, with age restriction to participants ≥60 years applied at full-text review to capture subgroup data. Thirteen studies met inclusion criteria, comprising 757 adults. Studies examined intranasal (n = 5), intravenous (n = 4), subcutaneous (n = 1), and oral (n = 1) ketamine formulations, as well as ketamine combined with ECT (n = 2). Antidepressant efficacy findings were mixed; with preliminary findings of symptomatic improvement in this difficult to treat disease state, although not all studies reported out positive outcomes.. Adverse events were generally mild to moderate and discontinuation due to side effects was rare. Cognitive outcomes were mostly stable or improved, though long-term studies noted small declines in reaction time. Ketamine as an ECT anesthetic did not enhance antidepressant outcomes. Evidence certainty was very low to low; findings were limited by small samples, open-label designs, and inconsistent age-stratified reporting.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |