Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study
This cost-utility analysis, alongside a randomised controlled trial (n=174), compared subcutaneous ketamine (twice-weekly for 4 weeks) with midazolam in treatment-resistant depression. Including midazolam costs, ketamine raised QALYs (0.435 vs 0.352) and was dominant with an 89-91 % chance of costing < $50 000/QALY, but once these comparator costs were excluded ketamine was no longer cost-effective (ICER ≈ $108 500-$251 250/QALY, ≤ 5 % probability).
Authors
- Paul Glue
- Colleen Loo
- Anthony Rodgers
Published
Abstract
Background
Ketamine is effective for treatment resistant depression (TRD); but cost-effectiveness evidence remains limited.
Aims
To evaluate the cost-effectiveness of subcutaneous ketamine for TRD from health sector and societal perspectives.
Methods
A cost-utility analysis alongside the KADS randomised controlled trial (RCT) involved 174 participants receiving ketamine or midazolam (active control) twice weekly for 4 weeks. Healthcare resource use, transportation, carer time and lost productivity data were collected via self-reported questionnaire at baseline, end of RCT (week 4) and RCT 4-week follow-up (week 8). Quality-adjusted life years (QALYs) were calculated using AQoL-8D utility values. Initial dosing was fixed (cohort 1) and changed to response-guided dosing (cohort 2). Base-case 1 included control arm treatment costs; base-case 2 excluded these costs.
Results
At end of RCT, cohort 2 utility values were significantly higher for ketamine than the control treatment (0.435 vs. 0.352; p < 0.05). Health sector incremental cost-effectiveness ratios (ICERs) in base-case 1 indicated ketamine was dominant (less costly, more effective) with probabilities of falling below $50,000/QALY of 89 % (end of RCT) and 91 % (total across 8-weeks). Societal perspective probabilities were lower (30-32 %). In base-case 2, ketamine was not cost-effective (ICERs: $251,250/QALY at end of RCT; $108,500/QALY across 8-weeks), with minimal probabilities (0-5 %) of falling below $50,000/QALY.
Conclusions
The initial four-week ketamine treatment phase appeared cost-effective from a health sector perspective when including control arm costs, although societal perspective results were less favourable. Excluding control treatment costs highlighted substantial uncertainty, emphasising the importance of selecting an appropriate comparator for an economic evaluation.
Research Summary of 'Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study'
Introduction
Major depressive disorder carries substantial clinical and economic burden, and roughly 30% of patients do not respond adequately to standard antidepressant or psychosocial treatments, creating a need for effective interventions for treatment resistant depression (TRD). Previous clinical research has evaluated racemic ketamine and esketamine (S-ketamine), with esketamine receiving regulatory approval in several countries for TRD, but large Phase III trials of racemic ketamine are fewer. Economic evaluations to date have mainly modelled intranasal esketamine or compared esketamine to intravenous ketamine, often extrapolating benefits far beyond trial durations; none had specifically evaluated subcutaneous racemic ketamine within a trial setting. Chatterton and colleagues report the planned within-trial cost-utility analysis embedded in the KADS randomised, double-blind, active-controlled Phase III trial. The study set out to assess the cost-effectiveness of subcutaneous racemic ketamine versus midazolam (an active control intended to improve blinding) for adults with TRD from both an Australian health sector perspective and a societal perspective, using trial data on resource use, quality of life and productivity over a 4-week treatment period with a 4-week follow-up (total 8 weeks).
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Chatterton, M. L., Perez, J. K., Thai, T., Faller, J., Loo, C. K., Glozier, N., Barton, D., Baune, B. T., Mills, N. T., Fitzgerald, P. B., Glue, P., Sarma, S., Hadzi-Pavlovic, D., Dong, V., Martin, D., Mitchell, P. B., Berk, M., Carter, G., Hackett, M., . . . Mihalopoulos, C. (2025). Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study. Journal of Affective Disorders, 387, 119502. https://doi.org/10.1016/j.jad.2025.119502
References (4)
Papers cited by this study that are also in Blossom
Bahji, A., Vazquez, G. H., Zarate, C. A. · Journal of Affective Disorders (2021)
Loo, C., Glozier, N., Barton, D. et al. · British Journal of Psychiatry (2023)
Rognoni, C., Falivena, C., Costa, F. et al. · PharmaEconomics (2023)
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