Effect of ketamine on anxiety: findings from the Ketamine for Adult Depression Study.
Natalie T Mills, Stevan Nikolin, Nick Glozier, David Barton, Bernhard T Baune, Paul B Fitzgerald, Paul Glue, Shanthi Sarma, Anthony Rodgers, Dusan Hadzi-Pavlovic, Angelo Alonzo, Vanessa Dong, Donel Martin, Philip B Mitchell, Michael Berk, Gregory Carter, Maree Hackett, Andrew A Somogyi, Cathrine Mihalopoulos, Mary Lou Chatterton, Sean Hood, Colleen Loo
The British journal of psychiatry : the journal of mental science January 7, 2025 Retracted DOI: 10.1192/bjp.2024.250 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 174 |
| Population | People with treatment-resistant major depressive disorder (TRD) |
| Interventions | Racemic ketamine Midazolam |
| Dose | 0.5 mg/kg (fixed low dose, cohort 1); 0.5-0.9 mg/kg (flexible, response-guided dosing, cohort 2) |
| Duration | 4-week intervention, 4-week follow-up after treatment end |
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | #ketamine-therapy ketamine treatment Ketamine infusion #anxiety-depression mood disorders Mental health conditions Psychological disorders #clinical-research clinical trials Medical studies Controlled studies |
| Citations | 3 |
| Key findings | Subcutaneous ketamine at flexible, response-guided doses (0.5-0.9 mg/kg) significantly reduced anxiety in people with TRD, but the effect was not maintained at four weeks after treatment end. |
Abstract
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties. To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD. 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). 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). Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.