5.4.1. Generalised Anxiety Disorder and Social Anxiety Disorder

Several studies over the last ~5 years have demonstrated the efficacy of ketamine for the treatment of anxiety disorders such as generalised anxiety disorder (GAD) and social anxiety disorder (SAD). For example, a double-blind RCT in patients with SAD found greater reductions in the symptoms of SAD in patients given IV ketamine than patients given a saline placebo [11]. A later double-blinded RCT in patients with SAD and GAD compared subcutaneous ketamine to a midazolam placebo, finding a dose-responsive (0.25, 0.5 and 1 mg/kg) reduction in anxiety in those given ketamine within an hour of dosing, which persisted for a week [86]. Following this, Glue and colleagues investigated the safety, tolerability and efficacy of extended-release oral ketamine tablets in seven responders from their RCT [87]. Over 96 h, participants showed reductions in self-reported measures of fear, anxiety and depression. However, it is important to note that the small sample size meant that no inferential statistical analyses could be conducted, and the results should

be considered preliminary but promising. To our knowledge, no studies have examined intranasal esketamine for anxiety disorders, nor have they paired ketamine with adjunctive therapy, which is a potential area for future research.
