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.
For treatment-resistant major depression without psychosis, intravenous ketamine is at least as effective as electroconvulsive therapy (ECT). In a randomized trial with 403 patients, 55.4% of those receiving ketamine and 41.2% of those receiving ECT showed a 50% or greater reduction in depression scores over three weeks. ECT was linked to a notable decline in memory recall after three weeks (average decrease of 9.7 points on a memory test vs. 0.9 points with ketamine), with gradual recovery during follow-up. Quality-of-life improvements were similar between groups. Ketamine caused dissociation, while ECT led to musculoskeletal side effects.
Electroconvulsive therapy (ECT) and ketamine show similar response rates for treatment-resistant depression, but a head-to-head comparison in a large, well-powered trial has been lacking. This protocol describes a non-inferiority trial randomizing 400 patients with treatment-resistant depression to receive either ECT thrice weekly or intravenous ketamine twice weekly for 3-5 weeks. The primary outcome is the proportion of responders based on a patient-reported depression scale. The study is designed to determine whether ketamine retains at least 90% of ECT's treatment effect. Results will inform patient choice, clinical practice, and insurance policies.