Unidentified genotype does not affect pharmacological treatment for patients with first episode psychosis.

Background: Research on the pharmacogenetic influence of hepatic enzyme 2D6 () on metabolism of drugs for psychosis and associated outcome has been inconclusive. Some results suggest increased risk of adverse reactions in poor and intermediate metabolizers, while others find no relationship. However, retrospective designs may fail to account for the long-term pharmacological treatment of patients. Previous studies found that clinicians adapted risperidone dose successfully without knowledge of patient phenotype.

Aim: Here, we aimed to replicate the results of those studies in a Dutch cohort of patients with psychosis ( = 418) on pharmacological treatment.

Method: We compared chlorpromazine-equivalent dose between metabolizer phenotypes and investigated which factors were associated with dosage. This was repeated in two smaller subsets; patients prescribed pharmacogenetics-actionable drugs according to published guidelines, and risperidone-only as done previously.

Results: We found no relationship between chlorpromazine-equivalent dose and phenotype in any sample (complete sample:  = 0.3, actionable-subset:  = 0.82, risperidone-only:  = 0.34). Only clozapine dose was weakly associated with phenotype ( = 0.03).

Conclusion: Clinicians were thus not intuitively adapting dose to activity in this sample, nor was activity associated with prescribed dose. Although the previous studies could not be replicated, this study may provide support for existing and future pharmacogenetic research.