Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study
Barton, D., Baune, B. T., Berk, M., Chatterton, M. L., Dong, V., Faller, J., Fitzgerald, P. B., Glozier, N., Glue, P., Hackett, M., Hadzi-Pavlovic, D., Hood, S., Loo, C., Martin, D., Mihalopoulos, C., Mills, N. T., Mitchell, P. B., Perez, J., Rodgers, A., Sarma, S., Somogyi, A. A., Thai, T.
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).
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.