Ketamine and Esketamine: Foundations, Patient Selection, and Algorithm Placement

Ketamine and esketamine should be reserved for patients who have not responded to two to four adequate antidepressant trials. For mild depression, these treatments may not be appropriate. Esketamine may be considered for acute suicidality in treatment-resistant depression, even though clinical trials did not show a clear benefit; placebo groups receiving excellent inpatient care improved substantially, which masked the drug's effect. These drugs should be avoided in people with active substance use disorder and used with caution even in early recovery, reconsidering only after years of sustained remission.

Study at a glance

Abstract

Reserve ketamine or esketamine for patients who have failed two to four adequate antidepressant trials. Weigh severity too; mild cases may not warrant it. Consider esketamine for acute suicidality in TRD despite the negative trial results. Placebo groups received excellent inpatient standard of care and improved substantially, masking the drug's benefit. Avoid ketamine and esketamine in active substance use disorder. Hesitate even in early recovery. Reconsider only after years of sustained remission.