Drug-Metabolizing Enzyme Genotypes
and Aggressive Behavior Treatment Response
in Hospitalized Pediatric Psychiatric Patients
TracyGlauser Pharma study
Objective: The aim of this study was to examine the association between the CYP2D6 and CYP2C19 genotypepredicted 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.
Patient response to commonly used psychotropic medications demonstrates significant variability; only 30–75% of patients experience efficacy, whereas 65–75% encounter ad-
verse events (Kirchheiner et al. 2004; Emslie et al. 2006; Kratochvil et al. 2006; Hetrick et al. 2007). Many psychotropic medications are metabolized by cytochrome P450 (CYP) en-
zymes coded for by the polymorphic genes CYP2D6(þ124030) and CYP2C19 (*124020).
The relationships between the distinct CYP2D6 or CYP2C19 genotypes and the pharmacokinetics of psychotropic medications are the basis for genotype-based dosing recommendations for some medications (Kirchheiner et al. 2001).Despite the prevalence of the problem, the contribution of drug-metabolizing enzyme genotypes to the variability in aggressive behavior treatment response in hospitalized pediatric psychiatric patients is unknown. The purpose of this study was to examine the association between CYP2D6 and CYP2C19 genotype-predicted metabolizing phenotypes and short-term measures of drug efficacy (incidence of behavioral interventions for aggressive behavior) and toxicity (adverse drug reaction)
Drug tolerability was defined as the total number of recorded adverse drug reactions.
Identifying factors underlying the variability in drug efficacy
or tolerability is a key component for optimizing the patient’s
response to therapy. This is the first study to demonstrate that,
for children hospitalized for psychiatric conditions,
CYP2D6 and CYP2C19 genetic variation contributes to psychotropic…
Consideration of a patient’s genotype at the onset of a psychiatric hospitalization could play a significant role in personalizing and improving subsequent therapy.
Prospective longitudinal studies are necessary to better inform
how to optimally incorporate this genetic information into the
medical management of patients with aggression. In summary,
this study indicates that CYP2D6 and CYP2C19genotypes are
important in the clinical care of children with psychiatric diagnoses requiring medications that are metabolized throughthese two enzyme pathways.
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