Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study

J Psychopharmacol. 2020 Mar;34(3):267-272. doi: 10.1177/0269881119874457. Epub 2019 Sep 17.


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.

Keywords: BDNF; Ketamine; dose-response; enantiomers; generalized anxiety disorder; pharmacokinetics; social anxiety disorder.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Anxiety Agents / therapeutic use
  • Anxiety Disorders / drug therapy*
  • Blood Pressure / physiology
  • Brain-Derived Neurotrophic Factor / blood
  • Dissociative Disorders / chemically induced
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Resistance / drug effects
  • Female
  • Heart Rate / physiology
  • Humans
  • Ketamine / adverse effects
  • Ketamine / blood
  • Ketamine / pharmacokinetics
  • Ketamine / therapeutic use*
  • Male
  • Midazolam / therapeutic use
  • Middle Aged
  • Young Adult


  • Anti-Anxiety Agents
  • Brain-Derived Neurotrophic Factor
  • Ketamine
  • BDNF protein, human
  • Midazolam