Original Article | Published:

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

Neuropsychopharmacology volume 43, pages 325333 (2018) | Download Citation

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.

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Acknowledgements

The authors gratefully acknowledge support from the Robert E. Leet and Clara Guthrie Patterson Trust (JHT, AL-W, MHB), National Institutes of Health/National Institute of Mental Health (NIH/NIMH, 5T32MH018268, 5T32MH19961, 5T32MH019112, JHT; 1K23MH091240, MHB) and NARSAD (MHB). Additionally, the LSAS is a copyrighted scale, and we thank Michael Lebowitz, MD for allowing us to use the scale free of charge. ClinicalTrials.gov Identifier: NCT02083926

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  1. Child Study Center, Yale University, New Haven, CT, USA

    • Jerome H Taylor
    • , Angeli Landeros-Weisenberger
    • , Catherine Coughlin
    • , Jilian Mulqueen
    • , Jessica A Johnson
    • , Daniel Gabriel
    • , Margot O Reed
    • , Ewgeni Jakubovski
    •  & Michael H Bloch
  2. Department of Psychiatry, Yale University, New Haven, CT, USA

    • Jerome H Taylor
    •  & Michael H Bloch
  3. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

    • Jerome H Taylor

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Correspondence to Jerome H Taylor.

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https://doi.org/10.1038/npp.2017.194

Supplementary Information accompanies the paper on the Neuropsychopharmacology website (http://www.nature.com/npp)