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.
A severely depressed and chronically suicidal patient who had not responded to many antidepressant treatments, including electroconvulsive therapy (ECT) and ketamine alone, was given a combination of ECT (up to 150% bilateral stimulation) 2–3 times per week and intravenous racemic ketamine (up to 75 mg per infusion) on ECT-free days. Robust anti-suicidal and antidepressant effects appeared during the first week. After 9 ECT treatments and 7 ketamine infusions, the patient achieved a stable state and was discharged. A maintenance plan of monthly ECT with two ketamine infusions (up to 100 mg) around each ECT prevented relapse. The alternating regimen proved safe and long-term effective in this case.