Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial

In this randomized controlled trial (2018) the effects of intravenous ketamine (0.5 mg/kg over 40 min) were assessed in 18 adults with Social Anxiety Disorder (SAD). A significant reduction in anxiety symptoms was observed using the Liebowitz Social Anxiety Scale (LSAS) when compared to placebo. On the Visual Analog Scale (VAS) no reduction was observed, researchers attributed this to issues with blinding.

Abstract

“Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-d-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.”

Authors: Jerome H. Taylor, Angeli Landeros-Weisenberger, Catherine Coughlin, Jilian Mulqueen, Jessica A. Johnson, Daniel Gabriel, Margot O. Reed, Ewgeni Jakubovski & Michael H. Bloch

Summary of Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial

Introduction

Social anxiety disorder (SAD) negatively impacts academic achievement, work productivity, social relationships, and quality of life, and is associated with subsequent development of depression, alcoholism, and cardiovascular disease. Current evidence-based treatment for SAD is ineffective, and novel pharmacological treatments are needed.

Neuroimaging and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of social anxiety disorder. Elevated glutamate to creatinine ratios have also been found in the anterior cingulate cortex of SAD patients.

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Study details

Compounds studied
Ketamine

Topics studied
Anxiety

Study characteristics
Placebo-Controlled Double-Blind

Participants
18 Humans

Compound Details

The psychedelics given at which dose and how many times

Ketamine 0.5 mg

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