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Characterizing the course of suicidal ideation response to ketamine.

Elizabeth D. Ballard, Julia S Yarrington, Cristan A Farmer, Erica M. Richards, Rodrigo Machado‐Vieira, Bashkim Kadriu, Mark J. Niciu, Peixiong Yuan, Lawrence T. Park, Carlos A. Zarate

Journal of Affective Disorders December 1, 2018 DOI: 10.1016/j.jad.2018.07.077 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Secondary analysis of pooled clinical trial data using growth mixture modeling Peer reviewed
Sample size 128
Population Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or bipolar depression
Intervention Ketamine
Dose 0.5 mg/kg
Duration Single infusion over 40 min; follow-up to Day 3
Topics Depression Ketamine Esketamine
Keywords Growth mixture modeling Suicidal ideation Suicide
Key findings Three distinct suicidal ideation response classes emerged after ketamine: Non-Responders (29%), Responders (44%), and Remitters (27%), with maximal improvement by Day 1. Suicidal ideation improvement was independent of depressed-mood improvement for Responders and partially independent for Remitters. Chronic suicidal ideation and self-injury indicators predicted Non-Responder membership, while higher baseline plasma IL-5 was linked to Remitter status.

Abstract

No pharmacological treatments exist for active suicidal ideation (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We developed data-driven subgroups of SI trajectories after ketamine administration, then evaluated clinical, demographic, and neurobiological factors that might predict SI response to ketamine. Data were pooled from five clinical ketamine trials. Treatment-resistant inpatients (n = 128) with DSM-IV-TR-diagnosed major depressive disorder (MDD) or bipolar depression received one subanesthetic (0.5 mg/kg) ketamine infusion over 40 min. Composite SI variable scores were analyzed using growth mixture modeling to generate SI response classes, and class membership predictors were evaluated using multinomial logistic regressions. Putative predictors included demographic variables and various peripheral plasma markers. The best-fitting growth mixture model comprised three classes: Non-Responders (29%), Responders (44%), and Remitters (27%). For Responders and Remitters, maximal improvements were achieved by Day 1. Improvements in SI occurred independently of improvements in a composite Depressed Mood variable for Responders, and partially independently for Remitters. Indicators of chronic SI and self-injury were associated with belonging to the Non-Responder group. Higher levels of baseline plasma interleukin-5 (IL-5) were linked to Remitters rather than Responders. Subjects were not selected for active suicidal thoughts; findings only extend to Day 3; and plasma, rather than CSF, markers were used. The results underscore the heterogeneity of SI response to ketamine and its potential independence from changes in Depressed Mood. Individuals reporting symptoms suggesting a longstanding history of chronic SI were less likely to respond or remit post-ketamine.

Comparable studies

Other non-randomized and open-label trials on ketamine for depression, most cited first.

Study Year Design Participants
Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder 2010 Open-label trial n = 33
Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression 2020 Phase 3, open-label, multicenter, long-term study n = 802
Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression 2020 Open-label pilot trial n = 7
A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... 2024 Open label study n = 17
Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... 2014 Pooled analysis of three clinical trials n = 97

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