1. Glue, Paul. “Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalized anxiety and social anxiety disorders” Journal of Psychopharmacology. 2018 Jun 1; 32(6): 663-667.
SUMMARY: In this study, 20 patients who met diagnostic criteria for generalized anxiety disorder (GAD) and/or social anxiety disorder (SAD) were given weekly low dose ketamine for 3 months. The aim was to evaluate the effect on anxiety ratings, safety and tolerability of repeated ketamine treatment on these anxiety disorders. One hour after dosing, Fear Questionnaire ratings decreased by ~50%, as did Hamilton Anxiety ratings. Clinician Administered Dissociative States Scale mean scores declined over time, from 20 points at week 1 to 8.8 points at week 14. Compared with pre-dose values, mean systolic and diastolic blood pressure increased by ~10 mm Hg at 30 min. The most common adverse events were nausea, dizziness and blurred vision. Of the 20 patients, 18 reported improved social functioning and/or work functioning during maintenance treatment. This study concluded that weekly ketamine dosing was safe and well tolerated, and post-dose dissociative symptoms tended to reduce after repeated dosing. Patients reported marked improvements in functionality and in their personal lives. Maintenance ketamine may be a therapeutic alternative for patients with treatment refractory GAD/SAD.
2. Glue, Paul, et al. “Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders” Journal of Psychopharmacology. 2017 Oct; 31(10): 1302-1305.
SUMMARY: This study evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 hour of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5-1 mg/kg. Ketamine was safe and well tolerated in this population. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.
3. Taylor JH, et al. “Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial” Neuropsychopharmacology. 2018 Jan; 43(2): 325-333.
SUMMARY: This is a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 social anxiety disorder comparing the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo 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-hours post-infusion and followed for 14 days. Response was defined as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. 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) and VAS (88.89% response ketamine vs 52.94% response placebo). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.
4. Glue, Paul, et al. “Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study” Journal of Psychopharmacology. 2019 Sep 17.
SUMMARY: 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. 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.