Ketamine for Depression in Serious Illness: Evidence, Safety, and Practical Approaches.
Journal of pain and symptom management August 1, 2026 Paul Noufi, Joshua B Borris, Danielle Chammas et al.
Ketamine and esketamine offer rapid antidepressant effects, with intravenous ketamine producing moderate-to-large improvements within 1–24 hours that last one to two weeks, and a number needed to treat of three in the first week. Esketamine nasal spray shows similar early efficacy and is FDA-approved for treatment-resistant depression and major depression with suicidal ideation. Evidence specific to people with serious illnesses is limited to perioperative cancer trials and small open-label studies, showing short-term reductions in depressive symptoms and suicidal ideation but not addressing long-term management. Safety is generally favorable, with transient dissociation, hypertension, and somnolence as common adverse effects. Rigorous psychiatric trials in serious illness are lacking.