In people with treatment-resistant depression who do not have psychosis, intravenous ketamine works as well as electroconvulsive therapy (ECT) overall. Among outpatients with moderately severe or severe depression, ketamine produced greater improvement in depressive symptoms than ECT. In contrast, inpatients with very severe depression improved more with ECT early in treatment, though by the end of the three-week course both treatments were similarly effective. Higher premorbid intelligence and a diagnosis of posttraumatic stress disorder were linked to greater improvement with ECT, but not with ketamine. These findings may help patients and clinicians decide between the two treatments.
Over eleven million U.S. Veterans are 65 or older, and nearly 20% of that group experiences clinically significant depression. Existing medications often work poorly for late-life depression, especially when it is treatment-resistant. Ketamine offers a potentially rapid-acting option, but few studies have tested it in older adults. This ongoing trial uses an adaptive randomization design to compare the safety, tolerability, efficacy, and durability of three different low doses of intravenous ketamine against a single dose of an active placebo (midazolam) in older depressed veterans. As the study proceeds, Bayesian adaptive randomization shifts the odds of assignment toward the more promising dose conditions.