Implementation of CYP2D6 genotyping in psychiatry

Abstract

Background: Response to pharmacotherapy is subject to large inter-individual variation. Most medicine is metabolised by CYP450 enzymes, including CYP2D6. CYP2D6 activity is determined substantially by the genetic composition. Polymorphisms of CYP2D6 are associated with inadequate response on treatment with psychotropics. The large number of polymorphisms of CYP2D6 raises the question of the way associations between genotype and clinical outcome measurements should be analysed and implemented into a clinical setting. Objective: Several methods used for grouping CYP2D6 genotypes are discussed, including the Predicted Phenotype method, the Semi-quantitative Gene Dose system and the Activity Score system. Possible ways to translate genetic information into dose recommendations and to implement genetic information into a clinical setting are discussed. Conclusions: A 100% accurate prediction of metabolic activity is not possible due to the effect of non-genetic factors on metabolic activity. When used for clinical purposes, none of the methods for grouping CYP2D6 genotypes has substantial advantages. The Semi-quantitative Gene Dose or Activity Score system might be preferred for research purposes. Large clinical studies on cost-efficiency will be needed to assure the cost-efficiency of routinely genotyping CYP2D6. Creating more awareness among prescribers of psychotropics about the genetic causes for aberrant drug response, and the possibility of genotyping, is desirable.