Abstract
Background: Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic as well as antidepressant properties.
Objectives: To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
Methods: The Ketamine for Adult Depression Study (KADS) was a multisite 4-week, double-blind, active (midazolam), randomised controlled trial (RCT). The study initially used a fixed low dose of ketamine (0.5 mg/kg, cohort I ), before protocol revision to a 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 the ‘inner tension’ item 3 of the Montgomery-Âsberg Depression Rating Scale (MADRS), both 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.
Findings: In cohort I (n = 68) the reduction in HAM-A was not statistically significant: -1.4 [95% confidence interval (Cl) -8.6, 3.2, p = 0.37) whereas a significant reduction was seen for cohort 2(n= 06) of -4.0 (95% Cl -10.6, -1.9, p = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS score but 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 I (p = 0.96).
Conclusions: Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses, but effects were not sustained.
Oral presentation.