Systematic review and meta-analysis of randomized controlled trials of ketamine in the treatment of refractory anxiety spectrum disorders

Author:

Whittaker Elizabeth1,Dadabayev Alisher R.2,Joshi Sonalee A.3,Glue Paul4ORCID

Affiliation:

1. Department of Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

2. Anesthesiology Service, Ralph H. Johnson VA Medical Center, Charleston, SC, USA

3. Department of Psychology, University of Michigan, Ann Arbor, MI, USA

4. Hazel Buckland Chair, Psychological Medicine, School of Medical Sciences, University of Otago, PO Box 913, Dunedin 9054, New Zealand

Abstract

Background: Anxiety disorders are common, associated with significant burden of disease, and have high levels of treatment resistance. Low-dose ketamine has been extensively studied in treatment-resistant depression, with fewer reports in treatment-resistant anxiety disorders. Aims: This systematic review and meta-analysis collected efficacy, safety, and tolerability data for ketamine as a treatment for anxiety spectrum disorders. Methods: We conducted a systematic search for randomized controlled trials (RCTs) of acute ketamine treatment for patients with anxiety disorders. Open-label trials of ketamine maintenance therapy were also considered. Qualitative and, where possible, quantitative syntheses of findings were performed using Review Manager software (RevMan). Acute dose-response and maintenance treatment data were also collected. Results: There were six eligible acute RCTs – two in social anxiety disorder (SAD), three in post-traumatic stress disorder (PTSD), and one in obsessive-compulsive disorder (OCD). Four of the six showed significant improvement in anxiety rating scores in ketamine compared with control groups. Pooled analysis showed ketamine was associated with an increased likelihood of treatment response for SAD (odds ratio (OR): 28.94; 95% confidence interval [CI]: 3.45–242.57; p = 0.002) but not for PTSD (OR: 2.03; 95% CI: 0.67–6.15; p = 0.21). A dose-response profile was observed for ketamine and changes in SAD symptoms, with doses ⩾0.5 mg/kg associated with greater reduction in anxiety rating scores than lower doses. Ketamine maintenance therapy was associated with sustained anxiolytic effects and improved social and/or work functioning. Conclusion: These preliminary analyses suggest that acute ketamine may be broadly effective across treatment-resistant anxiety spectrum disorders. These effects can be prolonged with maintenance treatment. Future studies will be needed to provide critical knowledge gaps around off-label use, side effects, and potential risks for abuse in clinical settings.

Publisher

SAGE Publications

Subject

Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Psychology (miscellaneous)

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