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The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: results from a randomized double-blind study

A. Feeney, Rebecca S. Hock, Marlene P. Freeman, M. Flynn, Bettina B. Hoeppner, Dan V. Iosifescu, Madhukar H. Trivedi, Gerard Sanacora, S. Mathew, Charles DeBattista, Dawn F. Ionescu, Maurizio Fava, George I. Papakostas

European Neuropsychopharmacology June 2, 2021 DOI: 10.1016/j.euroneuro.2021.04.024 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 56
Population Patients with treatment-resistant depression and clinically significant suicidal ideation
Interventions IV ketamine IV midazolam
Duration 30-day follow-up
Topics Depression Esketamine Ketamine
Citations 33
Registration NCT01920555
Key findings A single intravenous ketamine infusion was associated with lower suicidal ideation scores at 30 days compared to midazolam placebo, but early anti-suicidal effects diminished rapidly and recurrence was common.

Abstract

This study aimed to assess the effect of a single infusion of intravenous (IV) ketamine on suicidal ideation in patients with treatment-resistant depression (TRD). Patients with TRD were randomized in a double-blind fashion to a single infusion of IV ketamine or IV midazolam placebo. Suicidal ideation was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) suicide item at 3, 5, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p=0.049; Hedges’ g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation. Trial registration: NCT01920555.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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