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Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study

Paul Glue, Shona Neehoff, A. Sabadel, Lucy Broughton, Martin Le Nedelec, Shabah M. Shadli, Neil McNaughton, Natalie J. Medlicott

Journal of Psychopharmacology March 1, 2020 DOI: 10.1177/0269881119874457 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, psychoactive-controlled ascending dose study Peer reviewed
Sample size 12
Population Patients with treatment-resistant generalized anxiety and social anxiety disorders who were not currently depressed
Interventions Ketamine Midazolam
Dose 0.25, 0.5, 1 mg/kg ketamine; 0.01 mg/kg midazolam
Duration Weekly intervals for ascending doses, with anxiety improvements persisting up to 1 week
Topics Anxiety Esketamine Ketamine
Citations 97
Key points Ketamine produced rapid and sustained anxiolytic effects with a dose-response profile in patients with treatment-resistant anxiety disorders.

Abstract

Background: We previously reported that ketamine has anxiolytic effects in patients with treatment-resistant generalized anxiety and social anxiety disorders.

Aims: The purpose of this study was to replicate our earlier report about ketamine‘s anxiolytic activity, using a more robust study design.

Methods: This was a double-blind, psychoactive-controlled ascending dose study in 12 patients with treatment-resistant generalized anxiety and social anxiety disorders who were not currently depressed. Ascending doses of ketamine (0.25, 0.5, 1 mg/kg) were administered at weekly intervals, and midazolam 0.01 mg/kg, the control, was randomly inserted into the ketamine dose sequence. Assessments included ratings of anxiety and dissociation, safety and tolerability, and blood samples for ketamine pharmacokinetics and BDNF concentrations.

Results: Improvements in anxiety ratings occurred within an hour of ketamine dosing, and persisted for up to 1 week. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate after ketamine dosing. Midazolam had minor brief effects on anxiety ratings. Ketamine was safe and well tolerated. Ketamine pharmacokinetics were correlated with dissociation ratings. Serum BDNF concentrations declined over time and were similar for all treatments.

Conclusions: Ketamine may be a potential therapeutic option for patients with treatment-resistant generalized anxiety and social anxiety disorders.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • State of the evidence: Ketamine for anxiety Supports

    Anxiety ratings improved within an hour of ketamine dosing and persisted up to one week, with a dose-response profile for anxiolytic effects, while midazolam had only minor brief effects.

    Synthesized

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
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
Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression Subjects with treatment-resistant depression 2018 Randomized controlled trial n = 99
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

Citations in the library

Cited by 36

and 31 more in the library

Cites 9

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