Randomized trial of ketamine masked by surgical anesthesia in patients with depression
Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr, Robin L. Okada, Cynthia A. Nyongesa, Lisa J. Cianfichi, Laura M Hack, Alan F. Schatzberg, Boris D. Heifets
Nature Mental Health October 19, 2023 DOI: 10.1038/s44220-023-00140-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Adults with major depressive disorder scheduled for routine surgery |
| Intervention | Ketamine |
| Dose | 0.5 mg kg−1 |
| Duration | 3 days post-infusion |
| Topics | Depression Esketamine Ketamine |
| Citations | 94 |
| Registration | NCT03861988 |
| Key findings | Intravenous ketamine delivered during surgical anesthesia had no greater effect than placebo on reducing depressive symptoms in adults with major depressive disorder. |
Abstract
Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. Here we present a single-center, parallel-arm, triple-masked, randomized, placebo-controlled trial assessing the antidepressant efficacy of intravenous ketamine masked by surgical anesthesia (ClinicalTrials.gov, NCT03861988). Adult patients (N = 40) with major depressive disorder who were scheduled for routine surgery were randomized to a single infusion of ketamine (0.5 mg kg−1) or placebo (saline) during usual anesthesia. All participants, investigators and direct-patient-care staff were masked to treatment allocation. The primary outcome was depression severity measured by the Montgomery–Åsberg Depression Rating Scale at 1, 2 and 3 days post-infusion. After all follow-up visits, participants were asked to guess which intervention they received. A mixed-effects model showed no evidence of effect of treatment assignment on the primary outcome (−5.82, 95% confidence interval −13.3 to 1.64, P = 0.13). Of all participants, 36.8% guessed their treatment assignment correctly; both groups allocated their guesses in similar proportions. In conclusion, a single dose of intravenous ketamine delivered during surgical anesthesia had no greater effect than placebo in acutely reducing the severity of depressive symptoms in adults with major depressive disorder. This trial successfully masked treatment allocation in patients with moderate-to-severe depression using surgical anesthesia. Although this masking strategy is impractical for most placebo-controlled trials, future studies of novel antidepressants with acute psychoactive effects should make efforts to fully mask treatment assignment to minimize participant-expectancy bias. In this clinical trial, a single dose of intravenous ketamine delivered during surgical anesthesia had no greater effect than placebo in acutely reducing the severity of depressive symptoms in adults with major depressive disorder.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.