A preliminary attempt to personalize risperidone dosing using drug-drug interactions and genetics: Part I

Jose De Leon, Neil B. Sandson, Kelly L. Cozza

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Background: Personalized prescription is described even in lay journals, but there has been no attempt to propose personalizing dosing for any specific psychiatric drug. Objective: Any attempt to develop personalized dosing needs to be anchored in our understanding of the pharmacological response of each drug in each person's environment, particularly drug-drug interactions (DDIs) and how genetic make-up influences drug response. Method: Risperidone (R) is used as an example. R's pharmacologic response is reviewed in detail by focusing on our current knowledge of its pharmacodynamic and pharmacokinetic actions. The influences of the environment and genetics on these two actions are reviewed. Results: R's antipsychotic action is probably mainly explained by the blocking of dopamine receptors, particularly D2 receptors. There are polymorphic variations of this gene (DRD2), but it is not clear that they have clinical relevance in predicting adverse drug reactions (ADRs) or antipsychotic response. Conclusion: Previous exposure to antipsychotics increases the need for higher R dosing, but the mechanism for this tolerance is not well understood. Other brain receptors, such as other dopamine, serotonin, and adrenergic receptors may explain some of these ADRs. Some polymorphic variations in these receptors have been described, but they cannot yet be used to personalize R dosing.

Original languageEnglish
Pages (from-to)258-270
Number of pages13
Issue number3
StatePublished - 2008

Bibliographical note

Funding Information:
In the past year, Dr. de Leon has been on the advisory board of Roche Molecular Systems, Inc. He has received investigator-initiated grants from Roche Molecular Systems, Inc. , and Eli Lilly Research Foundation ; he has lectured supported by Eli Lilly, Janssen, and Roche Molecular Systems, Inc. Roche Molecular Systems, Inc., markets the AmpliChip CYP450 microarray that detects CYP2D6 and CYP2C19 gene variations.

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Applied Psychology
  • Psychiatry and Mental health


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