Ketamine and Esketamine for TRD in Older Adults: Efficacy and Tolerability

Introduction: Promising Results for a Challenging Demographic

A recent systematic review and meta-analysis published in 2026 has shed light on the potential efficacy and tolerability of ketamine and esketamine in treating treatment-resistant depression (TRD) among older adults. This demographic often faces limited options due to the reduced effectiveness of conventional antidepressants and increased risk of adverse effects. The study, which analyzed data from 13 primary studies conducted between 2023 and 2025, suggests that these rapid-acting antidepressants could offer significant relief for older patients.

Mechanisms and Context: Understanding the Findings

The review utilized standardized mean change (SMC) to measure antidepressant effects and found a pooled SMC of −1.68, indicating a large and clinically meaningful reduction in depressive symptoms. Approximately 47% of participants experienced at least one adverse event (AE), though most were mild. Discontinuation due to AEs was relatively low, with a pooled rate of 16%. The study's risk-of-bias assessments, conducted using ROBINS-I and RoB 2 tools, varied across studies but were consistently low in randomized trials. Additionally, funnel plot analysis revealed no significant publication bias.

Implications for Policy and Future Research

The findings underscore the need for further geriatric-focused randomized trials to refine dosing strategies and assess long-term outcomes. Given the positive sentiment and relevance score of 7/10, these results could significantly impact clinical decision-making and patient care for older adults with TRD. Policymakers and healthcare providers should consider integrating these findings into treatment guidelines, while researchers should prioritize studies that address the unique physiological and psychological needs of older populations.

Risks and Unknowns: Navigating Uncertainties

While the results are promising, there are still several unknowns that warrant caution. The study highlights the need for more comprehensive data on long-term effects and optimal dosing in older adults. Additionally, the potential for adverse effects, although generally mild, remains a concern that must be carefully managed in clinical settings. Researchers and clinicians must work collaboratively to address these uncertainties through well-designed trials and observational studies.

Conclusion: A Forward-Looking Perspective

The systematic review and meta-analysis provide a hopeful outlook for the use of ketamine and esketamine in treating TRD among older adults. As the population ages, the demand for effective and safe antidepressant treatments will only increase. By continuing to explore and refine these therapeutic options, the medical community can better meet the needs of this vulnerable demographic, ultimately improving quality of life and mental health outcomes.