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

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: F=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F=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.

Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety

“…Ketamine produced no sign of an improvement in HFD scores at any dose and no systematic or reliable changes in FAA. Reduced anxiety has previously been reported with ketamine ( Glue et al, 2017 ; Taylor et al, 2018 ); however, we saw significant changes only in FQ and no large changes in HAM-A scores.…”

“…SAD, in particular, has high economic burden, because it causes social impairment, poor academic achievement, reduced work productivity, and increased financial dependence on the government ( Lipsitz and Schneier, 2000 ). Conventional treatments can take weeks to produce their full effects and, worse, one-third of SAD patients are treatment resistant ( Kelly et al, 2015 ; Taylor et al, 2015 , 2018 ), which increases outpatient costs, doubles hospitalizations, and produces substantial morbidity ( Liebowitz et al, 2003 ). We urgently need novel pharmaceutical agents that are both more effective and act quickly ( Liebowitz et al, 2003 ; Taylor et al, 2018 ).…”

Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature

“…The authors discussed concerns about the use of saline as a placebo comparator, since most participants correctly identified they were on active medication, which could have affected the reliability of the study. 44…”

Ketamine blocks morphine-induced conditioned place preference and anxiety-like behaviors in mice

“…Evidence suggests that ( R,S )-ketamine, a noncompetitive NMDA receptor antagonist (Lodge et al, 1982;Kohrs and Durieux, 1998), is an effective treatment for anxiety and substance use disorders (Krupitsky et al, 2002a;Ivan Ezquerra-Romano et al, 2018;Taylor et al, 2018). Because of this, we investigated whether an acute injection of ( R,S )-ketamine (30 min.…”

“…Ketamine has recently been shown to be a potential effective treatment for anxiety disorders (Glue et al, 2018;Shadli et al, 2018;Taylor et al, 2018). In humans, ketamine displays a biphasic dose effect on anxiety, with low doses decreasing anxiety and higher doses increasing anxiety (Jansen, 1989;Krystal et al, 1994).…”