Abstract
Background: The CYP2D6 enzyme is involved in the metabolism of numerous psychopharmacological drugs. Guidelines recommend how to adjust the dose of medication based on the CYP2D6 genotype.Aims: To evaluate the effect of dose adjustment to the CYP2D6 genotype and phenotype, in patients with severe mental illness (SMI) already receiving psychopharmacological treatment.Methods: A total of 269 psychiatric patients (on the island Curaçao) receiving antipsychotic treatment were genotyped for CYP2D6. Of these, 45 patients were included for dose adjustment according to the clinical guideline of the Royal Dutch Association for the Advancement of Pharmacy, i.e., 17 CYP2D6 poor metabolizers, 26 intermediate metabolizers, and 2 ultrarapid metabolizers. These 45 patients were matched for age, gender, and type of medication with a control group of 41 patients who were CYP2D6 extensive metabolizers (i.e., with a normal CYP2D6 function). At baseline and at 4 months after dose adjustment, subjective experience, psychopathology, extrapyramidal side-effects, quality of life, and global functioning were assessed in these two groups.Results: At baseline, there were no differences between the groups regarding the prescribed dosage of antipsychotics, the number of side-effects, psychiatric symptoms, global functioning, or quality of life. After dose adjustment, no significant improvement in these parameters was reported.Conclusion: In psychiatric patients with SMI already receiving antipsychotic treatment, dose adjustment to the CYP2D6 genotype or phenotype according to the guidelines showed no beneficial effect. This suggests that dose adjustment guidelines are currently not applicable for patients already using antipsychotics.ClinicalTrials.gov: Cost-effectiveness of CYP2D6 and CYP2C19 Genotyping in Psychiatric Patients in Curacao; Identifier: NCT02713672; https://clinicaltrials.gov/ct2/show/NCT02713672?term=CYP2D6&rank=5
Highlights
The cytochrome P450 isozymes, in particular CYP2D6, is responsible for the biotransformation of many psychopharmacological drugs [1, 2]
In psychiatric patients with severe mental illness (SMI) already receiving antipsychotic treatment, dose adjustment to the CYP2D6 genotype or phenotype according to the guidelines showed no beneficial effect
This suggests that dose adjustment guidelines are currently not applicable for patients already using antipsychotics
Summary
The cytochrome P450 isozymes, in particular CYP2D6, is responsible for the biotransformation of many psychopharmacological drugs [1, 2]. The recommended dosages of psychopharmacological medication that are metabolized by this enzyme are based on the metabolism of the most common genotype, i.e., the EM type (i.e., a normal CYP2D6 function). When physicians prescribe a drug metabolized by CYP2D6 without taking into account the genotype, the hospital stay is longer (and the costs higher) in patients with a PM and UM profile [8]. The CYP2D6 enzyme is involved in the metabolism of numerous psychopharmacological drugs. Guidelines recommend how to adjust the dose of medication based on the CYP2D6 genotype
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