Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial
Michael F Grunebaum, Hanga C Galfalvy, Tse-Hwei Choo, John G Keilp, Vivek K. Moitra, Michelle S. Parris, Julia E. Marver, A. Burke, Matthew S. Milak, M. Sublette, M. Oquendo, J. Mann
American Journal of Psychiatry December 5, 2017 DOI: 10.1176/appi.ajp.2017.17060647 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized clinical trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Adults with current major depressive disorder and a Scale for Suicidal Ideation score of 4 or higher |
| Interventions | Ketamine Midazolam |
| Dose | sub-anesthetic intravenous |
| Duration | 24 hours for primary outcome; benefit sustained up to six weeks with clinical pharmacotherapy |
| Topics | Depression Esketamine Ketamine |
| Citations | 428 |
| Key findings | Adjunctive ketamine reduced clinically significant suicidal ideation more than midazolam within 24 hours, with a response rate of 55% versus 30%. |
Abstract
Objective: Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation.
Method: This randomized clinical trial tested the effect of adjunctive sub-anesthetic intravenous ketamine on clinically significant suicidal ideation in major depressive disorder (MDD). Adults (N=80) with current MDD and score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomized to ketamine or midazolam infusion. The primary outcome was Day 1 SSI score (24 hours post-infusion). Other outcomes included global depression and adverse effects.
Results: Reduction of SSI score was 4.96 points greater after ketamine compared with midazolam at Day 1 (95% confidence interval (CI)=2.33 to 7.59; p=0.0003; Cohen’s d=0.75). Proportion of responders (≥50% reduction in SSI) at Day 1 was 55% after ketamine and 30% after midazolam (OR=2.85 (95% CI=1.14 to 7.15); p=0.0237; NNT=4.00). Improvement in the Profile of Mood States (POMS) depression subscale was greater at Day 1 compared with midazolam treatment (Estimate=7.65 (95% CI=1.36 to 13.94), df=75, t=2.42, p=0.0178), and this effect mediated 33.6% of ketamine’s effect on SSI score. Side effects were short-lived. Benefit was sustained for up to six weeks with clinical pharmacotherapy.
Conclusions: Adjunctive ketamine demonstrated greater reduction of clinically significant suicidal ideation in depressed patients within 24 hours compared to midazolam, partially independent of antidepressant effect. Research is needed to understand ketamine’s mechanism of action and to develop safe, longer-term treatment.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.