Risperidone Metabolism and the Impact of Being a Cytochrome P450 2D6 Ultrarapid Metabolizer

Letter to the Editor

Sir: We read with great interest the recent article by Bork et al. concerning the impact of hepatic enzyme cytochrome P450 (CYP) 2D6 activity onrisperidone metabolism. The authors discuss the possibility that ultrarapid metabolizers, who have multiple copies of an active CYP2D6 gene2 and who represent 1% to 7% of the white population,could have subtherapeutic concentrations of the CYP2D6 substrate risperidone. However, no such subjects were identified in their study. In previous studies, CYP2D6 ultrarapid metabolizers have been shown to have very low concentrations and to be unresponsive to average doses of other CYP2D6 substrates, such as tricyclic antidepressants.In this report, we present 2 patients with low risperidone concentrations who subsequently were found to be CYP2D6 ultrarapid metabolizers.