In the study Ketamine’s dose-related effects on anxiety symptoms in patients with treatment-refractory anxiety disorders by Glue et al. (2017), researchers explored whether ketamine—long known for its rapid antidepressant properties—could also alleviate symptoms in patients suffering from chronic, treatment-resistant anxiety. Their findings revealed that ketamine, administered in ascending doses, rapidly reduced anxiety within an hour, with effects lasting up to seven days.
This small but important study supports the growing hypothesis that anxiety and depressive disorders may share overlapping neurobiological features and that ketamine’s unique mechanism of action may benefit both.
Study Overview and Patient Demographics
The open-label trial included 12 patients diagnosed with generalized anxiety disorder (GAD) and/or social anxiety disorder (SAD). All participants were free from major depressive symptoms, ensuring that results could be attributed to anxiety-specific effects rather than mood improvements.
Notably, these individuals were classified as treatment-refractory, having failed to respond to conventional anti-anxiety medications or therapeutic strategies.
Methodology: A Carefully Escalating Dose Strategy
Patients received subcutaneous ketamine injections at escalating doses of:
- 0.25 mg/kg
- 0.5 mg/kg
- 1.0 mg/kg
Each dose was administered once weekly over a three-week period, allowing time to assess both immediate and lingering effects.
Outcome Measures and Assessments
Primary outcomes focused on self-reported anxiety symptoms, collected at baseline, 1 hour post-dose, and throughout the following week. The use of standardized scales enabled consistent monitoring of each patient’s response to treatment.
Key Results: Rapid Onset, Sustained Relief
Across all three dosing levels, participants reported notable reductions in anxiety within one hour of administration. While individual variability existed, the overall effect showed a dose-response relationship: higher doses were generally associated with more pronounced symptom relief.
Importantly, these improvements persisted for up to seven days, indicating a meaningful duration of benefit even after a single subcutaneous dose.
Safety and Tolerability
Ketamine was well tolerated, with no serious adverse events reported. Mild side effects such as dizziness or dissociation were transient and resolved without intervention.
These findings align with broader research that shows ketamine’s side effect profile is manageable under medical supervision.
Broader Implications and Future Directions
This study contributes to a growing body of literature suggesting ketamine’s broad-spectrum efficacy across disorders involving negative affect. From major depression and PTSD to OCD and now anxiety, the treatment appears to target common neurocircuitry disruptions.
Further studies with larger sample sizes, placebo-controlled designs, and long-term follow-up will be necessary to confirm these early results and define optimal dosing regimens.
Conclusion
The trial Ketamine’s dose-related effects on anxiety symptoms in patients with treatment-refractory anxiety disorders adds valuable support to the use of ketamine as a potential therapeutic alternative for GAD and SAD. Its rapid onset, sustained relief, and good tolerability position it as a compelling candidate for patients unresponsive to standard treatments.
References
- Glue P, Medlicott NJ, Harland S, et al. Ketamine’s dose-related effects on anxiety symptoms in patients with treatment-refractory anxiety disorders. J Psychopharmacol. 2017;31(10):1302-1305. https://doi.org/10.1177/0269881117705089
- Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic PTSD. JAMA Psychiatry. 2014;71(6):681-688. https://doi.org/10.1001/jamapsychiatry.2014.62
- Zarate CA, Singh JB, Carlson PJ, et al. A randomized trial of an NMDA antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856-864. https://doi.org/10.1001/archpsyc.63.8.856
- Taylor JH, Landeros-Weisenberger A, Coughlin C, et al. Ketamine for social anxiety disorder: A randomized, placebo-controlled crossover trial. Neuropsychopharmacology. 2018;43(2):325-333. https://doi.org/10.1038/npp.2017.194
Glue P, Neehoff S, Medlicott NJ, et al. Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalized anxiety and social anxiety disorders. J Psychopharmacol. 2018;32(6):663-667. https://doi.org/10.1177/0269881118760660
