In patients with advanced cancer and major depressive disorder, three flexible doses of intranasal ketamine (50–150 mg) over one week produced rapid antidepressant effects. By day 8, 70% of participants showed a response (depression scores reduced by more than half) and 45% achieved remission. Depression scores dropped from an average of 31 to 11, a decrease of 20 points. Some benefit persisted into the second week without further doses. Side effects were mostly mild and temporary, including fatigue, dissociation, nausea, altered taste, and headaches; one participant withdrew due to a negative dissociative episode. Larger controlled trials are warranted.
In adults with advanced cancer receiving palliative care, intranasal ketamine was associated with clinically meaningful improvements in existential distress, anxiety, symptom burden, and quality of life. Fifteen participants who completed three doses of ketamine showed improvements exceeding established minimal clinically important differences on measures of anxiety, death and dying distress, overall symptoms, and quality of life. Improvements in existential well-being were larger than those in physical symptoms. Changes in depression did not significantly correlate with changes in existential distress outcomes, suggesting ketamine may have independent effects on multiple dimensions of distress in this population.