Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety

Abstract

Objective: Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms.

Methods: 133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion.

Results: At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004).

Conclusions: Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.

Trial registration: ClinicalTrials.gov NCT00088699.

Keywords: Depression; Ketamine; Suicidal ideation; Suicide.

Conflict of interest statement

Conflict of Interest

Dr. Furey is listed as a co-inventor on a patent application for the use of scopolamine in major depression and Dr. Zarate is listed as a co-inventor on a patent application for the use of ketamine and its metabolites in major depression. Drs. Furey and Zarate have assigned their rights in the patent to the U.S. Government but will share a percentage of any royalties that may be received by the Government. The remaining authors have no conflicts of interest to disclose, financial or otherwise.

Published by Elsevier Ltd.

Figures

Figure 1

Figure 1a and 1b. Change in ideation at 230 minutes after ketamine infusion compared to changes in depression and anxiety. Note: Markers in graphs represent frequencies; larger markers represent more patients scoring at that value.

Figure 2

Figures 2a and 2b. Reductions in cognitions related to suicidal ideation as measured by the SSI in placebo-controlled trials of ketamine, limited to patients any suicidal thoughts at baseline. 2a. Wish to Live 2b. Wish to Die