A Model Based Cost-Effectiveness Analysis of Routine Genotyping for CYP2D6 Among Older, Depressed Inpatients Starting Nortriptyline Pharmacotherapy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Dec 30

PMID 28033366

Citations 4

Authors

Elizabeth J J Berm

Judith J Gout-Zwart

Jos Luttjeboer

Bob Wilffert

Maarten J Postma

Affiliations

Soon will be listed here.

Abstract

Objective: Genotyping for CYP2D6 has the potential to predict differences in metabolism of nortriptyline. This information could optimize pharmacotherapy. We determined the costs and effects of routine genotyping for old aged Dutch depressed inpatients.

Methods: With a decision-tree, we modelled the first 12 weeks of nortriptyline therapy. Direct costs of genotyping, hospitalization, therapeutic drug monitoring and drugs were included. Based on genotype, patients could be correctly, sub-, or supratherapeutically dosed. Improvement from sub- or supratherapeutically dosed patients to correctly dosed patients was simulated, assuming that genotyping would prevent under- or overdosing of patients. In the base case, this improvement was assumed to be 35%. A probabilistic sensitivity analysis (PSA) was performed to determine uncertainty around the incremental cost-effectiveness ratio (ICER).

Results: In the base case analysis, costs for genotyping were assumed €200 per test with a corresponding ICER at €1 333 000 per QALY. To reach a €50 000 per QALY cut-off, genotyping costs should be decreased towards €40 per test. At genotyping test costs < €35 per test, genotyping was dominant. At test costs of €17 per test there was a 95% probability that genotyping was cost-effective at €50 000 per QALY.

Conclusions: CYP2D6 genotyping was not cost-effective at current genotyping costs at a €50 000 per QALY threshold, however at test costs below €40, genotyping could be costs-effective.

Citing Articles

How is Value Defined in Molecular Testing in Cancer? A Scoping Review.

Minhinnick A, Santos-Gonzalez F, Wilson M, Lorgelly P Appl Health Econ Health Policy. 2024; .

PMID: 38980555 DOI: 10.1007/s40258-024-00901-4.

Cost Effectiveness of Pharmacogenetic Testing for Drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: A Systematic Review.

Morris S, Alsaidi A, Verbyla A, Cruz A, Macfarlane C, Bauer J Clin Pharmacol Ther. 2022; 112(6):1318-1328.

PMID: 36149409 PMC: 9828439. DOI: 10.1002/cpt.2754.

Pharmacogenetic testing for adverse drug reaction prevention: systematic review of economic evaluations and the appraisal of quality matters for clinical practice and implementation.

Turongkaravee S, Jittikoon J, Rochanathimoke O, Boyd K, Wu O, Chaikledkaew U BMC Health Serv Res. 2021; 21(1):1042.

PMID: 34600523 PMC: 8487501. DOI: 10.1186/s12913-021-07025-8.

Economic evaluation in psychiatric pharmacogenomics: a systematic review.

Karamperis K, Koromina M, Papantoniou P, Skokou M, Kanellakis F, Mitropoulos K Pharmacogenomics J. 2021; 21(4):533-541.

PMID: 34215853 DOI: 10.1038/s41397-021-00249-1.

References

Chou W, Yan F, De Leon J, Barnhill J, Rogers T, Cronin M . Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness. J Clin Psychopharmacol. 2000; 20(2):246-51. DOI: 10.1097/00004714-200004000-00019. View

Bradford L . CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002; 3(2):229-43. DOI: 10.1517/14622416.3.2.229. View

Gildengers A, Houck P, Mulsant B, Pollock B, Mazumdar S, Miller M . Course and rate of antidepressant response in the very old. J Affect Disord. 2002; 69(1-3):177-84. DOI: 10.1016/s0165-0327(01)00334-2. View

Higashi M, Veenstra D . Managed care in the genomics era: assessing the cost effectiveness of genetic tests. Am J Manag Care. 2003; 9(7):493-500. View

Roberts R, Mulder R, Joyce P, Luty S, Kennedy M . No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline. Hum Psychopharmacol. 2004; 19(1):17-23. DOI: 10.1002/hup.539. View

Sapin C, Fantino B, Nowicki M, Kind P . Usefulness of EQ-5D in assessing health status in primary care patients with major depressive disorder. Health Qual Life Outcomes. 2004; 2:20. PMC: 416488. DOI: 10.1186/1477-7525-2-20. View

Ingelman-Sundberg M . Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2004; 5(1):6-13. DOI: 10.1038/sj.tpj.6500285. View

Breyer-Pfaff U . The metabolic fate of amitriptyline, nortriptyline and amitriptylinoxide in man. Drug Metab Rev. 2004; 36(3-4):723-46. DOI: 10.1081/dmr-200033482. View

Greenhalgh J, Knight C, Hind D, Beverley C, Walters S . Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies. Health Technol Assess. 2005; 9(9):1-156, iii-iv. DOI: 10.3310/hta9090. View

10.

Kropp S, Lichtinghagen R, Winterstein K, Schlimme J, Schneider U . Cytochrome P-450 2D6 and 2C19 polymorphisms and length of hospitalization in psychiatry. Clin Lab. 2006; 52(5-6):237-40. View

11.

Sobocki P, Ekman M, Agren H, Runeson B, Jonsson B . The mission is remission: health economic consequences of achieving full remission with antidepressant treatment for depression. Int J Clin Pract. 2006; 60(7):791-8. DOI: 10.1111/j.1742-1241.2006.00997.x. View

12.

Kootstra-Ros J, Van Weelden M, Hinrichs J, De Smet P, van der Weide J . Therapeutic drug monitoring of antidepressants and cytochrome p450 genotyping in general practice. J Clin Pharmacol. 2006; 46(11):1320-7. DOI: 10.1177/0091270006293754. View

13.

Rush A, Trivedi M, Wisniewski S, Nierenberg A, Stewart J, Warden D . Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11):1905-17. DOI: 10.1176/ajp.2006.163.11.1905. View

14.

Mathers C, Loncar D . Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006; 3(11):e442. PMC: 1664601. DOI: 10.1371/journal.pmed.0030442. View

15.

Daly T, Dumaual C, Miao X, Farmen M, Njau R, Fu D . Multiplex assay for comprehensive genotyping of genes involved in drug metabolism, excretion, and transport. Clin Chem. 2007; 53(7):1222-30. DOI: 10.1373/clinchem.2007.086348. View

16.

Matchar D, Thakur M, Grossman I, McCrory D, Orlando L, Steffens D . Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs). Evid Rep Technol Assess (Full Rep). 2007; (146):1-77. PMC: 4781099. View

17.

Rebsamen M, Desmeules J, Daali Y, Chiappe A, Diemand A, Rey C . The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Pharmacogenomics J. 2008; 9(1):34-41. DOI: 10.1038/tpj.2008.7. View

18.

Laika B, Leucht S, Heres S, Steimer W . Intermediate metabolizer: increased side effects in psychoactive drug therapy. The key to cost-effectiveness of pretreatment CYP2D6 screening?. Pharmacogenomics J. 2009; 9(6):395-403. DOI: 10.1038/tpj.2009.23. View

19.

Perlis R, Patrick A, Smoller J, Wang P . When is pharmacogenetic testing for antidepressant response ready for the clinic? A cost-effectiveness analysis based on data from the STAR*D study. Neuropsychopharmacology. 2009; 34(10):2227-36. PMC: 3312011. DOI: 10.1038/npp.2009.50. View

20.

Kok R, Aartsen M, Nolen W, Heeren T . The course of adverse effects of nortriptyline and venlafaxine in elderly patients with major depression. J Am Geriatr Soc. 2010; 57(11):2112-7. DOI: 10.1111/j.1532-5415.2009.02524.x. View