Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
3 papers in the library · 5 citations · publishing 2025-2026
Anxiety 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.
Subcutaneous ketamine appears cost-effective for treatment-resistant depression from a health sector perspective when the costs of the control treatment (midazolam) are included, but not from a societal perspective. A cost-utility analysis alongside a randomized controlled trial with 174 participants compared ketamine to midazolam given twice weekly for four weeks. At the end of the trial, quality of life scores were significantly higher for ketamine. When control arm costs were included, ketamine was less costly and more effective, with an 89% probability of being cost-effective at a $50,000 per quality-adjusted life year threshold. Excluding those costs made ketamine not cost-effective, highlighting the importance of comparator choice.
A 4-week course of subcutaneous racemic ketamine produced short-term clinical benefit in a minority of people with treatment-resistant depression, with response rates declining substantially after treatment cessation. Among 130 participants, 30% responded at treatment end (Montgomery-Åsberg Depression Rating Scale reduction ≥50%), but only 17% remained responders 4 weeks later, and over 50% experienced less than a 25% reduction in depression scores. No difference in response was found between fixed and flexible dosing regimens. Prior ketamine treatment during an earlier randomized trial did not affect later outcomes. No suicides or suicidal behavior requiring admission occurred, and only expected side effects were observed.