Ketamine No Better Than Placebo for Depression

Intravenous ketamine delivered during surgical anesthesia has no greater effect than placebo in reducing severity of depression

WEDNESDAY, Oct. 25, 2023 (HealthDay News) — For patients with major depressive disorder, a single dose of intravenous ketamine delivered during surgical anesthesia has no greater effect than placebo, according to a study published online Oct. 19 in Nature Mental Health.

Theresa R. Lii, M.D., from the Stanford University School of Medicine in California, and colleagues randomly assigned 40 adult patients with major depressive disorder who were scheduled for routine surgery to a single infusion of ketamine or placebo during usual anesthesia. Depression severity, measured by the Montgomery-Åsberg Depression Rating Scale, was the primary outcome, assessed at one, two, and three days after infusion. Participants were asked to guess which intervention they received after all follow-up visits.

The researchers found no evidence of treatment assignment on the primary outcome in a mixed-effects model (−5.82; 95 percent confidence interval, −13.3 to 1.64; P = 0.13). Overall, 36.8 percent of the participants guessed their treatment assignment correctly, with similar proportions in both groups.

“Our primary findings differ from those of previous antidepressant trials with ketamine conducted without adequate masking, which find robust effects of ketamine,” the authors write. “Our robust, masked placebo response suggests that previously reported large effect sizes for ketamine may reflect a degree of expectancy bias.”

Several authors disclosed ties to industry.

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