The clinical and cost effectiveness of testing for cytochrome P450 polymorphisms in patients treated with antipsychotics

Liverpool Reviews and Implementation Group, University of Liverpool, UK.
Health technology assessment (Winchester, England) 01/2010; 14(3):1-157, iii. DOI: 10.3310/hta14030
Source: PubMed


To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources.
The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members.
A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out.
For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99-100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing.
Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.

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    • "In Europe, the Pharmacovigilence Working Party has recommended that labeling information should highlight the " possible reduction in response to tamoxifen in poor CYP2D6 metabolisers " [20]. It remains to be seen whether this will be implemented by the member states, including the United Kingdom where CYP2D6 testing is currently not used widely outside of research [21]. "
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    • "In order to implement such tools in unique populations , novel CYP2D6 alleles first need to be characterised and their respective capacity to metabolise CYP2D6 substrates assessed . CYP2D6 genotype is believed to have relevance to predict antipsychotic response (Kobylecki et al., 2009), although more studies that measure clinical utility of genotyping of CYP2D6 with regards to schizophrenia treatment are still required (Fleeman et al., 2010). "
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