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.
Higher body mass index (BMI) and obesity are linked to a stronger acute antidepressant effect from a single intravenous dose of ketamine in patients with treatment-resistant depression. In a randomized, double-blind, placebo-controlled trial, patients with obesity showed a significantly greater reduction in depression symptoms 24 hours after ketamine infusion compared to those with normal BMI. Overweight patients also showed a trend toward greater improvement. Similar but weaker effects were observed at 72 hours. The findings suggest that obesity may enhance the rapid antidepressant response to ketamine, which could have clinical relevance for the many patients with both major depressive disorder and obesity.