Ketamine: Is It Superior to Midazolam for Depression?
May 27, 2026 DOI: 10.64239/pi-qt8704
Summary
A randomized trial found that serial intravenous ketamine was not significantly more effective than the active placebo midazolam in reducing depressive symptoms or improving quality of life. The improvement in MADRS scores fell short of the minimal clinically important difference. The study had a small sample size of 63 participants and faced blinding failures, with 78% of patients and 90% of raters correctly identifying the ketamine group, suggesting results may have been influenced by unblinded expectations. Further research that controls for non-specific effects is needed.
Study at a glance
| Characteristics | Randomized controlled trial |
|---|---|
| Sample size | 63 |
| Population | Patients with depression |
| Key finding | Serial intravenous ketamine was not significantly more effective than midazolam in reducing depressive symptoms or improving quality of life. |
Abstract
A new randomized trial found serial intravenous ketamine was not significantly more effective than the active placebo midazolam in reducing depressive symptoms or improving quality of life. While the study may have been underpowered due to a small sample size (n=63), the improvement in MADRS scores fell short of the minimal clinically important difference. The study faced blinding failures, with 78% of patients and 90% of raters correctly identifying the ketamine group, suggesting results may have been influenced by unblinded expectations. Further research that effectively controls for non-specific effects is needed.