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Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study.

Mary Lou Chatterton, Johana Kevin Perez, Thao Thai, Jan Faller, Colleen K Loo, Nick Glozier, David Barton, Bernhard T Baune, Natalie T Mills, Paul B Fitzgerald, Paul Glue, Shanthi Sarma, Dusan Hadzi-Pavlovic, Vanessa Dong, Donel Martin, Philip B Mitchell, Michael Berk, Gregory Carter, Maree Hackett, Sean Hood, Andrew A Somogyi, Anthony Rodgers, Cathrine Mihalopoulos

Journal of affective disorders October 15, 2025 DOI: 10.1016/j.jad.2025.119502 via PubMed

Summary

AI-generated from the abstract

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.

Study at a glance

Characteristics Cost-utility analysis alongside a randomized controlled trial Double-blind Peer reviewed
Sample size 174
Population Participants with treatment-resistant depression
Interventions subcutaneous ketamine midazolam
Duration 4-week intervention, 4-week follow-up
Topics Depression Ketamine
Keywords Clinical trials Clinical drug studies Cost effectiveness
Citations 2
Key finding Subcutaneous ketamine was cost-effective from a health sector perspective when including control arm costs, but not from a societal perspective or when excluding those costs.

Abstract

Ketamine is effective for treatment resistant depression (TRD); but cost-effectiveness evidence remains limited. To evaluate the cost-effectiveness of subcutaneous ketamine for TRD from health sector and societal perspectives. 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. 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. 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.

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