Skip to content

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 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 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
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 Esketamine
Keywords Clinical trials Clinical drug studies Cost effectiveness Treatment resistance Ketamine therapy Mental health economics Antidepressant research
Citations 2
Key findings 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.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

Citations in the library

Cited by 1

Cites 8

and 3 more in the library

Related reading

Explore topics

Depression Ketamine Esketamine

By condition and practice

Ketamine for depression