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

Chiara Fabbri, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Alessandro Serretti, Cathryn M. Lewis

Research output: Contribution to journalArticlepeer-review


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 for CL-R and £3937 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 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 and of £4110 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.

Original languageEnglish
Pages (from-to)722-729
Number of pages8
JournalJournal of Affective Disorders
StatePublished - 15 Jan 2021


  • Antidepressants
  • Cost-Effectiveness
  • Genetics
  • Psychotherapy
  • Treatment-Resistant Depression


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