1. Effect of ketamine on anxiety: findings from the Ketamine for Adult Depression Study.
- Author
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Mills NT, Nikolin S, Glozier N, Barton D, Baune BT, Fitzgerald PB, Glue P, Sarma S, Rodgers A, Hadzi-Pavlovic D, Alonzo A, Dong V, Martin D, Mitchell PB, Berk M, Carter G, Hackett ML, Somogyi AA, Mihalopoulos C, Chatterton ML, Hood S, and Loo CK
- Abstract
Background: Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties., Aims: To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD., Method: The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5-0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and 'inner tension' item 3 of the Montgomery-Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment ( n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448)., Results: In cohort 1 ( n = 68) the reduction in HAM-A score was not statistically significant: -1.4 (95% CI [-8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 ( n = 106) of -4.0 (95% CI [-10.6, -1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 ( P = 0.026) but not cohort 1 ( P = 0.96)., Conclusion: Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.
- Published
- 2025
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