Drug-Metabolizing Enzyme Genotypes and Aggressive Behavior Treatment Response in Hospitalized Pediatric Psychiatric Patients

Abstract

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. 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 ¼ 0.01) and number of adverse drug reactions ( p ¼ 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. Conclusion: Common variants in CYP2D6 and CYP2C19 are associated with the short-term efficacy and tolerability of psychotropic medications in hospitalized pediatric patients.

Influence of CYP2C19 Metabolizer Status on Escitalopram/Citalopram Tolerability and Response in Youth With Anxiety and Depressive Disorders

“…Our study adds to a growing body of research demonstrating the feasibility of using retrospective EMR data for pharmacogenetic research in the inpatient psychiatric setting (Prows et al, 2009; Jukic et al, 2018). As EMR data extraction becomes increasingly automated, we offer a model for investigating relationships between pharmacogenetics and treatment outcomes using retrospective EMR data in the psychiatric setting.…”

Pharmacogenomic Testing in Child and Adolescent Psychiatry: An Evidence-Based Review

“…7 A similar association of poor metabolizers having greater treatment response and higher incidence of side effects was demonstrated in a study of psychiatrically-hospitalized pediatric patients treated with psychotropic medications. 36 A study of autistic children treated with risperidone monotherapy revealed polymorphisms in the 5-HT 2A receptor as well as the 5-HT 2C receptor. A BDNF-related polymorphism produced treatment-related increases in prolactin while polymorphisms in the 5-HT 2C receptor as well as CYP2D6 phenotype predicted risperidone-related increases in BMI and/or waist circumference (Correia et al 2010).…”

Disinhibition as a Side Effect of Treatment with Fluvoxamine in Pediatric Patients with Obsessive-Compulsive Disorder

“…This hope was shown to be a potentially useful tool on inpatient pediatric psychiatric units in a retrospective analysis (Prows et al 2009). They examined the correlation between the CYP2D6 and CYP2C19 genotype-predicted combined phenotype and a behavioral intervention score to measure psychotropic efficacy as well as the drug's tolerability by reported adverse reactions.…”