Abstract
Article retracted on 31 March 2026 by the Editors of BJPsych. The Editors conducted an additional review and agreed that the errors did not alter the study’s findings or final conclusions. However, given the extent of the corrections required, they concluded that a corrigendum would not be sufficient. They agreed that retraction of the original article with subsequent resubmission of a corrected paper would be the best course of action.
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.