(Es)Ketamine for Suicidal Ideation and Behavior: Clinical Efficacy.

Suicidal ideation and behavior are among the most severe psychiatric presentations, warranting emergency room visits and psychiatric admission for higher levels of care. In the United States, suicide rates continue to climb, especially in younger patients, and the continued psychosocial stressors of the COVID-19 pandemic may further exacerbate this crisis. Suicidal ideation and behavior are core features of a major depressive episode, but there are limited treatment options to rapidly redress these life-threatening symptoms. Racemic ketamine and its S-enantiomer, esketamine, are N-methyl-D-aspartate receptor antagonists and glutamate modulators that have robust antidepressant efficacy in treatment-resistant major depressive disorder and bipolar depression. Additionally, both ketamine and esketamine have demonstrated rapid-acting antisuicidal efficacy in major mood disorders. In August 2020, this culminated in a first-in-class approval of Spravato® (intranasal esketamine) for the treatment of major depressive disorder with acute suicidal ideation and behavior. In this article, we review the literature in support of the antisuicidal efficacy of ketamine and esketamine.

Biomarkers of ketamine's antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology.

Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.