Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study
P. Glue, Shona Neehoff, A. Sabadel, L. Broughton, M. Le Nedelec, Shabah M. Shadli, N. Mcnaughton, N. Medlicott
Journal of Psychopharmacology March 1, 2020 DOI: 10.1177/0269881119874457 via Semantic Scholar
Summary
In a double-blind, psychoactive-controlled study, 12 patients with treatment-resistant generalized anxiety and social anxiety disorders who were not currently depressed received ascending doses of ketamine (0.25, 0.5, 1 mg/kg) at weekly intervals, with midazolam 0.01 mg/kg randomly inserted as a control. Improvements in anxiety ratings occurred within an hour of ketamine dosing and persisted for up to one week. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate. Midazolam had minor brief effects on anxiety ratings. Ketamine was safe and well tolerated. Ketamine may be a potential therapeutic option for these patients.
Study at a glance
| Characteristics | Double-blind, psychoactive-controlled ascending dose study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Patients with treatment-resistant generalized anxiety and social anxiety disorders who were not currently depressed |
| Keywords | Medicine Psychology |
| Citations | 97 |
| Key finding | Ketamine produced rapid and sustained anxiolytic effects with a dose-response profile in patients with treatment-resistant anxiety disorders. |
Abstract
Background: We previously reported that ketamine has anxiolytic effects in patients with treatment-resistant generalized anxiety and social anxiety disorders. Aims: The purpose of this study was to replicate our earlier report about ketamine‘s anxiolytic activity, using a more robust study design. Methods: 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. Results: 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. Conclusions: Ketamine may be a potential therapeutic option for patients with treatment-resistant generalized anxiety and social anxiety disorders.