Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety
This post-hoc meta-analysis (n=133) examined the relationship between the antidepressant efficacy of intravenous ketamine (35mg/70kg) and its effects on suicidal ideation (SI) among patients with depression. Ketamine increased the patient's wish to live and decreased their wish to die, and these reductions in suicidal ideation independent of reductions in depressive and anxiety symptoms.
Authors
- Carlos Zarate
- Daniel Ionescu
- David Luckenbaugh
Published
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 (0.5mg/kg over 40 minutes). 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 minutes post-infusion.
Results
At 230 minutes 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 (F(1,587)= 10.31, p = .001) and anxiety (F(1,567)= 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.
Research Summary of 'Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety'
Introduction
Suicidal ideation is a common and potentially life‑threatening presentation in psychiatry, yet there are few rapid-acting pharmacological treatments specifically approved for suicidal thoughts. Earlier research has shown that ketamine, an NMDA receptor antagonist, produces rapid antidepressant effects and can reduce suicidal ideation, anxiety and hopelessness within hours to days after a single subanesthetic infusion. However, because suicidal thinking is closely related to both depressive and anxiety symptoms, it remains uncertain whether ketamine's anti‑suicidal effects are merely a by‑product of mood and anxiety improvement or whether ketamine has a more specific effect on suicidal cognition. This study set out to evaluate whether ketamine reduces suicidal ideation independently of its effects on depression and anxiety. Using pooled patient‑level data from previous ketamine trials, the investigators tested correlations between changes in ideation, depression and anxiety at 230 minutes post‑infusion, and used linear mixed models in placebo‑controlled subsets to assess the effect of ketamine on suicidal ideation while statistically controlling for concurrent changes in depressive and anxiety symptoms. They also examined two cognitive components of ideation—the wish to live and the wish to die.
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Study Details
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Ballard, E. D., Ionescu, D. F., Vande Voort, J. L., Niciu, M. J., Richards, E. M., Luckenbaugh, D. A., Brutsché, N. E., Ameli, R., Furey, M. L., & Zarate, C. A. (2014). Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety. Journal of Psychiatric Research, 58, 161-166. https://doi.org/10.1016/j.jpsychires.2014.07.027
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Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)
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