Ketamine for Depression in Serious Illness: Evidence, Safety, and Practical Approaches

Area of Science:

• Palliative Care
• Psychiatry
• Pharmacology

Background:

• Serious illness and short prognoses are frequently associated with depression and suicidal ideation.
• Traditional antidepressants have a delayed onset, necessitating the development of rapidly acting therapies.
• Ketamine and esketamine are being investigated as potential rapid-acting antidepressants.

Purpose of the Study:

• To examine the evidence for ketamine/esketamine efficacy as antidepressants, particularly in patients with serious illnesses.
• To review the rapid antidepressant effects, duration, and safety of ketamine/esketamine.
• To identify gaps in the current research regarding long-term management in palliative care.

Main Methods:

• Review of psychiatric studies on intravenous ketamine for depression.
• Analysis of studies on esketamine nasal spray for treatment-resistant and major depression with suicidal ideation.
• Examination of limited evidence from peri-operative cancer trials and small open-label studies in serious illness populations.

Main Results:

• Intravenous ketamine shows rapid (1-24 hours), moderate-to-large antidepressant effects lasting 1-2 weeks in psychiatric studies.
• Esketamine nasal spray demonstrates similar early efficacy and is FDA-approved for specific depression types.
• Evidence in serious illness shows short-term reductions in depressive symptoms and suicidal ideation, but lacks long-term data. Safety is generally favorable with transient side effects.

Conclusions:

• Ketamine and esketamine represent the strongest evidence for rapid-acting antidepressants, suitable for urgent symptom relief.
• Rigorous psychiatric trials specifically in serious illness populations are lacking for comprehensive understanding of long-term management.
• Clinicians must consider patient prognosis, regulatory access, and maintenance strategies when integrating ketamine into palliative care.