Cost-effectiveness of genetic and clinical predictors for choosing combined psychotherapy and pharmacotherapy in major depression

Background: : Predictors of treatment outcome in major depressive disorder (MDD) could contribute to evidence-based therapeutic choices. Combined pharmacotherapy and psychotherapy show increased efficacy but higher cost compared with antidepressant pharmacotherapy; baseline predictors of pharmacotherapy resistance could be used to identify patients more likely to benefit from combined treatment. Methods: : We performed a proof-of-principle study of the cost-effectiveness of using previously identified pharmacogenetic and clinical risk factors (PGx-CL-R) of antidepressant resistance or clinical risk factors alone (CL-R) to guide the prescription of combined pharmacotherapy and psychotherapy vs pharmacotherapy. The cost-effectiveness of these two strategies was compared with standard care (ST, pharmacotherapy to all subjects) using a three-year Markov model. Model parameters were literature-based estimates of response to pharmacotherapy and combined treatment, costs (UK National Health System) and benefits (quality-adjusted life years [QALYs], one QALY=one year lived in perfect health). Results: : CL-R was more cost-effective than PGx-CL-R: the cost of one-QALY improvement was 2341 pound for CL-R and 3937 pound for PGx-CL-R compared to ST. PGx-CL-R had similar or better cost-effectiveness compared to CL-R when 1) the cost of genotyping was 100 pound per subject or less or 2) the PGx-CL-R test had sensitivity >= 0.90 and specificity >= 0.85. The cost of one-QALY improvement for CL-R was 3664 pound and of 4110 pound in two independent samples. Limitations: : lack of validation in large samples from the general population. Conclusions: : Using clinical risk factors to predict pharmacotherapy resistance and guide the prescription of pharmacotherapy combined with psychotherapy could be a cost-effective strategy.

Automated summary

Utilizing clinical risk factors to predict pharmacotherapy resistance and guide the prescription of pharmacotherapy combined with psychotherapy could be a cost-effective strategy, with CL-R showing better cost-effectiveness compared to PGx-CL-R in certain scenarios. The study suggests that using these predictors can help identify patients who are more likely to benefit from combined treatment, ultimately improving outcomes and reducing costs.