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The effect of CYP2D6 variation on antipsychotic-induced hyperprolactinaemia: a systematic review and meta-analysis

Abstract

Hyperprolactinemia is a known adverse drug reaction to antipsychotic treatment. Antipsychotic blood levels are influenced by cytochrome P450 enzymes, primarily CYP2D6. Variation in CYP450 genes may affect the risk of antipsychotic-induced hyperprolactinemia. We undertook a systematic review and meta-analysis to assess whether CYP2D6 functional genetic variants are associated with antipsychotic-induced hyperprolactinemia. The systematic review identified 16 relevant papers, seven of which were suitable for the meta-analysis (n = 303 participants including 134 extreme metabolisers). Participants were classified into four phenotype groups as poor, intermediate, extensive, and ultra-rapid metabolisers. A random effects meta-analysis was used and Cohen’s d calculated as the effect size for each primary study. We found no significant differences in prolactin levels between CYP2D6 metabolic groups. Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia. However, statistical power is limited. Future studies with larger samples and including a range of prolactin-elevating drugs are needed.

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Funding

This study was supported by the National Institute for Health Research Biomedical Research Centre at University College London Hospital (mental health theme). Support to MSC: National Institute for Health Research Academic Clinical Fellowship 2015. Support to EB: Mental Health Research UK John Grace QC Scholarship 2018, BMA Margaret Temple Fellowships 2016 and 2006, Medical Research Council and Korean Health Industry Development Institute Partnering Award (MC_PC_16014), Medical Research Council New Investigator Award (G0901310) and MRC Centenary Award (G1100583), MRC project grant G1100583, a National Institute of Health Research UK post-doctoral fellowship (PDA/02/06/016), the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005 and 2008, a Wellcome Trust Research Training Fellowship, and Wellcome Trust Case Control Consortium awards (085475/B/08/Z, 085475/Z/08/Z). Further support to co-authors: Medical Research Council doctoral studentships to IA-Z, AB, and JH-S. British Medical Association Margaret Temple grant 2016 to JHT. HI has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 747429.

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Calafato, M.S., Austin-Zimmerman, I., Thygesen, J.H. et al. The effect of CYP2D6 variation on antipsychotic-induced hyperprolactinaemia: a systematic review and meta-analysis. Pharmacogenomics J 20, 629–637 (2020). https://doi.org/10.1038/s41397-019-0142-9

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