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Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses

The Pharmacogenomics Journal volume 11, pages 1–14 (2011)Cite this article

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Abstract

There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and meta-analyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.

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Acknowledgements

We are pleased to acknowledge the contributions of the other members of the Health Technology Assessment review team: Professor Adrian Bagust, Dr Angela Boland, Dr Sophie Beale, Dr Katherine Payne and Dr Phillip de Warren-Penny. We also thank Professor Paula Williamson for her input into the research protocol design and Ms Janet Atkinson who provided invaluable administrative support, including obtaining bibliographic sources. We also thank the anonymous referees for their valuable comments on the previous draft of this paper. This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 06/28/01). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the UK Government Department of Health.

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Authors and Affiliations

  1. Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK

    N Fleeman, Y Dundar, R Dickson, C McLeod & T Walley

  2. Specialist Registrar in General Adult Psychiatry, Central Wirral Community Mental Health Team, Highfield Centre, Wallasey, UK

    Y Dundar

  3. Research Associate, Medical Statistics, University of Liverpool, Liverpool, UK

    A Jorgensen

  4. Postdoctoral Research Scientist, Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK

    S Pushpakom

  5. Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK

    M Pirmohamed & T Walley

  6. UK NHS Department of Health, UK Chair in Pharmacogenetics, Liverpool, UK

    M Pirmohamed

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  1. N Fleeman
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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website

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Fleeman, N., Dundar, Y., Dickson, R. et al. Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses. Pharmacogenomics J 11, 1–14 (2011). https://doi.org/10.1038/tpj.2010.73

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  • DOI: https://doi.org/10.1038/tpj.2010.73

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