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 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.
Comparable studies
Other randomized controlled trials on ketamine for anxiety, most cited first.
Citations in the library
Cites 12
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- Effect of Baseline Anxious Depression on Initial and Sustained Antidepressant Response to Ketamine The Journal of Clinical Psychiatry September 25, 2014
- Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial Psychotherapy and Psychosomatics 2021
- Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study Journal of Psychopharmacology March 1, 2020
- Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial The British Journal of Psychiatry July 14, 2023
and 7 more in the library