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


METHODS
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 D(2) receptors. There are polymorphic variations of this gene (DRD(2)), but it is not clear that they have clinical relevance in predicting adverse drug reactions (ADRs) or antipsychotic response.


CONCLUSIONS
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.
de Leon
Jose
J
University of Kentucky Mental Health Research Center, Eastern State Hospital, Lexington, KY 40508, USA. jdeleon@uky.edu
Sandson
Neil B
NB
Cozza
Kelly L
KL
D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005838:Genotype; D006801:Humans; D018802:Patient-Centered Care; D011110:Polymorphism, Genetic / Q000235:genetics; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects / Q000235:genetics; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics; D018967:Risperidone / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
D014150:Antipsychotic Agents; D011941:Receptors, Adrenergic; D017448:Receptors, Dopamine D2; D011968:Receptors, Histamine; D011985:Receptors, Serotonin; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone