Clinical applications of CYP genotyping in psychiatry

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.