Intravenous ketamine at 0.5 mg/kg and 1.0 mg/kg produces rapid antidepressant effects in adults with treatment-resistant depression, with most improvement seen one day after a single 40-minute infusion. Lower doses (0.1 mg/kg and 0.2 mg/kg) did not show consistent benefit. The study compared four ketamine doses against an active placebo (midazolam) in 99 outpatients across six U.S. sites. Higher doses caused more dissociative symptoms and temporary blood pressure increases, but infusions were generally well tolerated. The findings indicate a range of effective subanesthetic doses, with no clear advantage for doses below 0.5 mg/kg.
A single dose of intravenous ketamine given during surgical anesthesia was no more effective than placebo at reducing depressive symptoms in adults with major depressive disorder. The trial randomized 40 patients to receive either ketamine or saline while under anesthesia for routine surgery, ensuring that neither participants, investigators, nor staff knew which treatment was given. Depression severity was measured over three days after infusion. Only about 37% of participants correctly guessed their treatment, indicating successful masking. The results suggest that ketamine's antidepressant effect may be influenced by its psychoactive effects, which complicate placebo-controlled testing.