Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: a trial-based economic evaluation

To evaluate the cost-effectiveness of pre-emptive CYP2D6 and CYP2C19 genotype-informed tricyclic antidepressant dosing from a societal and a healthcare perspective. A trial-based cost-effectiveness analysis was conducted with data from the Pharmacogenetics for Individualized Tricyclic Antidepressant dosing (PITA) study. This multicenter randomized controlled trial (n=111) compared pharmacogenetic-informed treatment (PIT) with treatment-as-usual (TAU). Quality-adjusted life years (QALY) and costs were measured at 13 and 26 weeks. Prices were based on or indexed to 2022 tariffs. Single imputation nested in the bootstrap percentile method (using 5000 bootstrap replications) was performed to address missing data and to estimate uncertainty around cost-effectiveness outcomes. Incremental Net Monetary Benefit (iNMB) was calculated based on a willingness-to-pay (WTP) of €50.000/QALY. Our data showed a marginal difference of -0.0125 QALYs (95%-confidence interval (CI) -0.0404 to 0.0149, week 13) and 0.0012 QALYs (95%-CI -0.0517 to 0.0491, week 26) for PIT versus TAU. From the healthcare perspective, a cost saving of €148 (week 13) and €521 (26 week) was found for PIT. The societal perspective showed increased costs of €1300 (week 13) and €1704 (26 weeks) for PIT. The mean iNMB from a healthcare perspective was positive at 26 weeks, the other iNMB (13 weeks and societal perspective) were negative. We observed marginal differences of QALYs in both the healthcare and societal perspective with cost savings from the healthcare perspective and additional cost from the societal perspective. These mixed results warrant more long-term observational studies to determine whether pre-emptive genotyping in tricyclic antidepressant dosing will be cost-effective.