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Clinical applications of CYP genotyping in psychiatry

  • Psychiatry and Preclinical Psychiatric Studies - Review Article
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Abstract

A critical review of the limited available evidence and the authors’ experience and judgment are used to summarize the role of cytochrome P450 (CYP) genetic variants in the pharmacokinetics of and clinical response to psychotropic medications. CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 genetic polymorphisms and their contributions to the metabolism of psychotropic drugs are reviewed. CYP1A2, CYP2B6 and CYP3A4 genotyping have limited current clinical utility. CYP2C9 genotyping has no utility in psychiatry. Psychiatrists should master tricyclic antidepressant (TCA) prescription, and if they use TCAs, they should have expertise in CYP2D6 and CYP2C19 genotyping and in TCA therapeutic drug monitoring (TDM) to safely dose TCAs. Practice guidelines recommend dose changes, TDM or alternate drugs for (1) CYP2C19 ultrarapid metabolizers (UM) taking citalopram or escitalopram; (2) CYP2C19 poor metabolizers (PMs) taking sertraline; (3) CYP2D6 PMs taking venlafaxine, aripiprazole, haloperidol, risperidone or zuclopenthixol; and (4) CYP2D6 UMs taking venlafaxine, aripiprazole, haloperidol, risperidone, zuclopenthixol or atomoxetine. According to the prescribing information, CYP2D6 PMs should receive 75 % of the average long-acting aripiprazole dose and pimozide doses >4 mg/day should not be prescribed without CYP2D6 genotyping. In a situation of limited evidence, there is need to use the available pharmacological mechanistic information for better personalizing treatment in psychiatry. This is best done by combining CYP genotyping with TDM. Clozapine and risperidone concentration-to-dose ratios are provided as two examples of this approach of how to integrate CYP genotyping and TDM in psychiatry. New studies are needed to verify that CYP2C19 PM genotyping may have potential to identify clozapine PMs and explain the lower clozapine metabolic capacity in East Asians.

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Acknowledgments

The authors acknowledge Lorraine Maw, M.A., and Margaret T. Boden, R.N., M.L.T., at the Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA, who helped in editing the article.

Conflict of interest

No commercial organizations had any role in the writing of this paper for publication. In the past few years, Dr. Spina has participated in speakers/advisory boards and lectures supported by AstraZeneca, Bristol-Myers, Eli Lilly & Co, Janssen Pharmaceuticals, Lundbeck and Pfizer. Dr. de Leon personally develops his presentations for lecturing, has never lectured using any pharmaceutical or pharmacogenetic company presentations and has never been a consultant for pharmacogenetic or pharmaceutical companies. In the past, Dr. de Leon received researcher-initiated grants from Eli Lilly (one ended in 2003 and the other, as co-investigator, ended in 2007); from Roche Molecular Systems, Inc. (ended in 2007); and, in a collaboration with Genomas, Inc., from the NIH Small Business Innovation Research program (ended in 2010). He has been on the advisory boards of Bristol-Myers Squibb (2003/2004) and AstraZeneca (2003). Roche Molecular Systems supported one of his educational presentations, which was published in a peer-reviewed journal (2005). His lectures were supported once by Sandoz (1997), twice by Lundbeck (1999 and 1999), twice by Pfizer (2001 and 2001), three times by Eli Lilly (2003, 2006 and 2006), twice by Janssen (2000 and 2006), once by Bristol-Myers Squibb (2006) and seven times by Roche Molecular Systems, Inc. (once in 2005 and six times in 2006).

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy

    Edoardo Spina

  2. University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA

    Jose de Leon

  3. Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain

    Jose de Leon

  4. Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apóstol Hospital, University of the Basque Country, Vitoria, Spain

    Jose de Leon

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  1. Edoardo Spina
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Correspondence to Edoardo Spina.

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Spina, E., de Leon, J. Clinical applications of CYP genotyping in psychiatry. J Neural Transm 122, 5–28 (2015). https://doi.org/10.1007/s00702-014-1300-5

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