Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial
This randomised study (n=80) found that participants with depression (MDD) and suicidal ideation (SSI/SI) who were treated with ketamine (IV, 35mg/70kg) have significantly lower SSI scores versus treatment with midazolam (another anesthetic). This effect consistently held up to 6 weeks later.
Authors
- Michael Grunebaum
Published
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. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder.
Method
In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1).
Results
The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen’s d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine’s effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.
Conclusions
Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.
Research Summary of 'Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial'
Introduction
There is a substantial unmet need for rapid-acting pharmacotherapy to relieve suicidal ideation in major depressive disorder. Earlier research has indicated that standard antidepressants can reduce suicidal thoughts indirectly via improvement in depressive symptoms, but these effects typically take weeks and many patients do not achieve adequate response. Other somatic treatments (for example, clozapine, electroconvulsive therapy, lithium) have some evidence for antisuicidal benefit in other diagnoses, yet trials of antidepressants have often excluded suicidal patients or failed to assess suicidal ideation systematically, leaving limited evidence for pharmacological reduction of clinically significant suicidal ideation in depressed patients. Grunebaum and colleagues therefore conducted a randomised, midazolam‑controlled clinical trial to test whether a single adjunctive subanesthetic intravenous ketamine infusion would produce a more rapid reduction in clinically significant suicidal ideation than an active control. The primary outcome was score on the clinician‑rated Scale for Suicidal Ideation (SSI) at 24 hours after infusion (day 1). Secondary outcomes included other measures of depression and mood, safety and adverse events, and the course of symptoms during a subsequent 6‑week uncontrolled follow‑up during which standard pharmacotherapy was optimised.
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Study Details
- Study Typeindividual
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- APA Citation
Grunebaum, M. F., Galfalvy, H. C., Choo, T., Keilp, J. G., Moitra, V. K., Parris, M. S., Marver, J. E., Burke, A. K., Milak, M. S., Sublette, M. E., Oquendo, M. A., & Mann, J. J. (2018). Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. American Journal of Psychiatry, 175(4), 327-335. https://doi.org/10.1176/appi.ajp.2017.17060647
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