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Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression

Naji C. Salloum, Maurizio Fava, Marlene P. Freeman, Martina Flynn, Bettina B. Hoeppner, Rebecca S. Hock, Cristina Cusin, Dan V. Iosifescu, Madhukar H. Trivedi, Gerard Sanacora, Sanjay J. Mathew, Charles DeBattista, Dawn F. Ionescu, George I. Papakostas

Depression and Anxiety December 30, 2018 DOI: 10.1002/da.22875 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 99
Population Subjects with treatment-resistant depression
Interventions Ketamine Midazolam
Dose 0.1, 0.2, 0.5, 1.0 mg/kg ketamine; 0.045 mg/kg midazolam
Duration 1 and 3 days postinfusion
Topics Anxiety Depression Ketamine Esketamine
Keywords Depression economics Psychotherapist Antidepressant
Citations 49
Key findings No statistically significant interaction was found between treatment group (ketamine vs midazolam) and anxious/nonanxious status on depression scores at 1 or 3 days postinfusion.

Abstract

Objective: To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD).

Methods: In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six-item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion.

Results: N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73).

Conclusion: In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

Comparable studies

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

Study Year Design Participants
Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial Patients with mood and anxiety spectrum disorders who presented with clinically... 2015 Randomized controlled trial n = 24
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence Detoxified inpatients with heroin dependence 2007 Randomized controlled trial n = 59
Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study Patients with treatment-resistant generalized anxiety and social anxiety disorders who... 2020 Double-blind, psychoactive-controlled ascending dose study n = 12
Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant Patients with treatment resistant depression 2020 Randomized controlled trial
Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response Patients with treatment-resistant depression 2021 Pooled post hoc analysis of two phase 3, double-blind, active-controlled studies

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