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Ketamine's antidepressant effects have rapid onset but are short-lived. In a three-phase, single-site study, investigators compared single infusions of ketamine to an active placebo and examined the impact of multiple infusions per week and weekly boosters.
The 41 participants had treatment-resistant major depression and had failed at least two 6-week trials of different antidepressant classes and two 6-week augmentation trials (mean age, 42; 56% women). In phase 1, which used a crossover design, the patients were randomized to midazolam or subanesthetic ketamine and, about 10 days later, received the alternate infusion. Within 24 hours, 27% responded to ketamine (≥50% on a clinician-rated scale), and none responded to midazolam; all respons…