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.
Two intravenous infusions of ketamine (0.5 mg/kg) given 24 hours apart, added to usual treatment, led to full remission of suicidal ideas by day 3 in 63.0% of hospitalized patients with suicidal ideation, compared to 31.6% with placebo. The benefit was strongest in patients with bipolar disorder (odds ratio 14.1), not significant in those with depressive disorder (odds ratio 1.3), and intermediate for other disorders (odds ratio 3.7). At six weeks, remission remained high in the ketamine group (69.5% vs 56.3%) but was no longer statistically significant. Side effects were limited, with no manic or psychotic symptoms observed. An analgesic effect on mental pain may explain the anti-suicidal action.