Precision psychiatry: The complexity of personalizing antipsychotic dosing

Abstract

Recently, Salagre and Vieta commented on the complexity of implementing precision medicine in psychiatry. For 25 years, this author has focused on a circumscribed type of precision medicine: personalized dosing using pharmacokinetic mechanisms to stratified patients. This short communication focuses on personalized dosing of three oral antipsychotics (clozapine, risperidone and paliperidone) and presents their maintenance dosing in a table which provides dose-correction factors generated by pharmacokinetic studies. Inhibitors need dose-correction factors < 1 and inducers need correction factors >1. Clozapine maintenance dosing is based on the dose needed to reach 350 ng/ml (the minimum plasma therapeutic concentration in treatment-resistant schizophrenia). Clozapine maintenance dosing is influenced by 3 levels of complexity: 1) ancestry groups (Asians/Native Americans; Europeans and Blacks), 2) sex-smoking subgroups (lowest dose in female non-smokers and highest in male smokers) and 3) presence/absence of poor metabolizer status (due to genetic and non-genetic causes including co-prescription of inhibitors, obesity or inflammation). Risperidone and paliperidone maintenance dosing are based on the dose needed to reach plasma concentrations of 20–60 ng/ml. Risperidone PMs need approximately half the dose, which can be explained by genetics (CYP2D6 PMs) or co-prescription of CYP2D6 inhibitors. Fluoxetine co-prescription may require one fourth the risperidone maintenance dose. Carbamazepine co-prescription may require twice the risperidone maintenance dose. Although not well studied, two groups may need higher doses of oral paliperidone: Koreans may need 1.5 times higher doses while those taking carbamazepine may need 3 times higher paliperidone maintenance doses. Precision dosing in psychiatry requires using blood levels of individuals.