Drug-metabolizing enzyme genotypes and aggressive behavior treatment response in hospitalized pediatric psychiatric patients.
OBJECTIVE
The aim of this study was to examine the association between the CYP2D6 and CYP2C19 genotype-predicted combined phenotypes and short-term measures of psychotropic efficacy and toxicity.


METHODS
A rater-blinded, retrospective genotype association design examined a cohort of hospitalized pediatric psychiatric patients genotyped for CYP2D6 and CYP2C19 as part of clinical care. These combined genotypes were used to predict a combined phenotype. The primary efficacy outcome measure was the behavior intervention score (BIS), a function of the number of recorded timeouts/seclusions, therapeutic holds, and physical restraints. Drug tolerability was defined as the total number of recorded adverse drug reactions.


RESULTS
Primary analysis was performed on 279 pediatric patients taking CYP2D6- or CYP2C19- dependent psychotropics. Combined phenotype was associated with BIS (p = 0.01) and number of adverse drug reactions (p = 0.03). Combined poor metabolizers treated with psychotropics had the lowest BIS (highest efficacy) and the highest number of adverse drug reactions. Combined ultrarapid metabolizers had the highest BIS (lowest efficacy) and the lowest number of adverse drug reactions.


CONCLUSIONS
Common variants in CYP2D6 and CYP2C19 are associated with the short-term efficacy and tolerability of psychotropic medications in hospitalized pediatric patients.
Prows
Cynthia A
CA
Division of Patient Services, University of Cincinnati college of Medicine, Cincinnati, OH, USA. tracy.glauser@cchmc.org
Nick
Todd G
TG
Saldaña
Shannon N
SN
Pathak
Sanjeev
S
Liu
Chunyan
C
Zhang
Kejian
K
Daniels
Zachary S
ZS
Vinks
Alexander A
AA
Glauser
Tracy A
TA
D000293:Adolescent; D000374:Aggression / Q000502:physiology* / Q000523:psychology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002653:Child Behavior Disorders / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D002675:Child, Preschool; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D011619:Psychotropic Drugs / Q000378:metabolism* / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
D011619:Psychotropic Drugs; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6
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