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.
Patients with treatment-resistant depression who also have anxiety tend to respond less well to antidepressants. This analysis of existing trial data examined whether adding esketamine to an antidepressant improves outcomes for such patients. Among those with comorbid anxiety, the combination of esketamine and an antidepressant led to greater improvement in depressive symptoms compared to an antidepressant alone. The benefit was also seen in patients without anxiety, though the difference was less pronounced. The results suggest that esketamine augmentation may be particularly helpful for treatment-resistant depression patients who also struggle with anxiety.