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Trial, Mar/22: Ketamine vs midazolam: Mood improvement reduces suicidal ideation


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The full title of this randomized controlled trial paper is "Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression".







Objective: Studies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored.


Methods: Exploratory, post hoc analysis of data from a randomized clinical trial of ketamine vs midazolam in patients with major depressive disorder (MDD) and clinically significant suicidal ideation examined changes in factor analysis-derived symptom clusters from standard measures of depression (Hamilton Depression Rating Scale, HDRS; Beck Depression Inventory, BDI) and mood disturbance (Profile of Mood States, POMS), and their relationship to severity of suicidal ideation (Beck Scale for Suicidal Ideation; SSI). Ratings obtained before and one day after blinded intravenous infusion were decomposed into component factors or published subscales. Treatment effects on factors/subscales were compared between drugs, correlations with changes in suicidal ideation were tested, and stepwise regression was used to derive predictors of change in SSI.


Results: Factor scores for HDRS Psychic Depression, HDRS Anxiety, BDI Subjective Depression, POMS Depression and POMS Fatigue improved more with ketamine than midazolam. Stepwise regression showed across both drugs that improvement in HDRS Psychic Depression, POMS Depression, and HDRS Anxiety predicted 51.6% of the variance in reduction of suicidal ideation.


Limitations: Secondary analysis of clinical trial data.


Conclusions: Ketamine's rapid effects on suicidal ideation appear to be mostly a function of its effects on core mood and anxiety symptoms of MDD, with comparatively little contribution from neurovegetative symptoms with the potential exception of vigor/fatigue.


Trial registration: Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01700829.


Copyright © 2021 Elsevier Ltd. All rights reserved.


Conflict of interest statement


Drs. Mann and Burke receive royalties for the commercial use of the Columbia Suicide Severity Rating Scale which was not part of this analysis. The other authors report no financial or other relationships pertinent to the subject of this article.

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