Ketamine and esketamine are the first non-monoamine-based antidepressants with rapid-onset efficacy for adults with treatment-resistant depression, offering hope to those who do not recover fully with standard antidepressants. However, concerns remain about their safety, tolerability, and appropriate placement in treatment algorithms. An international group of mood disorder experts synthesizes evidence on efficacy, safety, and tolerability, and provides guidance for clinical implementation, including practice parameters at point of care. Areas of consensus and future research directions are discussed.
Ketamine reduces anxiety symptoms within 12 hours of administration, and the effect lasts for 1 to 2 weeks. A systematic review and meta-analysis of 14 randomized controlled trials found significant reductions in anxiety scores compared to placebo at acute (less than 12 hours), subacute (24 hours), and sustained (7–14 days) time points. Improvements in anxiety and depression symptoms were correlated at 24 hours and at 7–14 days. The relationship between peak dissociation and anxiety improvement was not significant. Most studies had a high risk of bias.