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 L Hackett, Andrew A Somogyi, Cathrine Mihalopoulos, Mary Lou Chatterton, Sean Hood, Colleen K Loo
The British journal of psychiatry : the journal of mental science January 7, 2025 DOI: 10.1192/bjp.2024.250 via PubMed
Summary
AI-generated from the abstractAnxiety disorders and treatment-resistant major depressive disorder (TRD) often occur together. In a randomized controlled trial comparing subcutaneous ketamine to midazolam in 174 people with TRD, ketamine reduced anxiety only when given at flexible, response-guided doses (0.5-0.9 mg/kg). At a fixed low dose (0.5 mg/kg), the reduction in anxiety was not statistically significant. The anxiety-reducing effect was linked to overall depression improvement and was not sustained four weeks after treatment ended. The findings suggest that adequate dosing is necessary for ketamine's anxiolytic effect in this population.
Study at a glance
| 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 |
| Keywords | #ketamine-therapy ketamine treatment Ketamine infusion #anxiety-depression mood disorders Mental health conditions Psychological disorders |
| Citations | 3 |
| Key finding | 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.