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.
A single dose of intravenous ketamine (0.5 mg/kg) delivered during surgical anesthesia did not reduce depressive symptoms more than placebo in adults with major depressive disorder. In a triple-masked, randomized trial of 40 patients, depression severity scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) did not differ between the ketamine and placebo groups at 1, 2, or 3 days after infusion. Clinical response rates were similar (60% versus 50% on day 1). Only 36.8% of participants correctly guessed their treatment assignment, indicating successful masking. One serious adverse event occurred in each group, unrelated to ketamine. The findings suggest that ketamine's acute psychoactive effects may contribute to previously reported antidepressant results through subject-expectancy bias.