PMID- 33759847
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20230908
IS  - 1536-7312 (Electronic)
IS  - 0196-206X (Print)
IS  - 0196-206X (Linking)
VI  - 42
IP  - 3
DP  - 2021 Apr 1
TI  - Evidence for Pharmacogenomic Effects on Risperidone Outcomes in Pediatrics.
PG  - 205-212
LID - 10.1097/DBP.0000000000000883 [doi]
AB  - OBJECTIVE: To determine the association between genetic variants reported to 
      affect risperidone and adverse events (AEs) in children and adolescents. METHODS: 
      Individuals aged 18 years or younger with >/=4 weeks of risperidone exposure in a 
      deidentified DNA biobank were included. The primary outcome was AE frequency as a 
      function of genotype. Individuals were classified according to metabolizer status 
      for CYP2D6, CYP3A4, and CYP3A5; wild type, heterozygote, or homozygote for 
      specific single nucleotide variants for DRD2, DRD3, HTR2A, and HTR2C; and wild 
      type versus nonwild type for multiple uncommon variants in ABCG2, ABCB1, and 
      HTR2C. Tests of association of each classification to AEs were performed using a 
      Fisher exact test and logistic regression, and statistically significant 
      classifications were included in a final logistic regression. RESULTS: The final 
      cohort included 257 individuals. AEs were more common in CYP2D6 poor/intermediate 
      metabolizers (PMs/IMs) than normal/rapid/ultrarapid metabolizers (NMs/RMs/UMs) in 
      univariate and multivariate analysis. HTR2A-rs6311 heterozygotes and homozygotes 
      had fewer AEs than wild types in logistic regression but not in univariate 
      analysis. In the final multivariable model adjusting for age, race, sex, and 
      risperidone dose, AEs were associated with CYP2D6 (adjusted odds ratio [AOR] 2.6, 
      95% CI 1.1-5.5, for PMs/IMs vs. NMs/RMs/UMs) and HTR2A-rs6311 (AOR 0.6, 95% CI 
      0.4-0.9, for each variant allele), both consistent with previous studies. 
      CONCLUSION: Children and adolescents who are CYP2D6 PMs/IMs may have an increased 
      risk for risperidone AEs. Of the genes and variants studied, only CYP2D6 has 
      consistent association and sufficient data for clinical use, whereas HTR2A-rs6311 
      has limited data and requires further study.
CI  - Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Rossow, Katelyn M
AU  - Rossow KM
AD  - Departments of Pediatrics.
FAU - Oshikoya, Kazeem A
AU  - Oshikoya KA
AD  - Medicine, and.
FAU - Aka, Ida T
AU  - Aka IT
AD  - Departments of Pediatrics.
FAU - Maxwell-Horn, Angela C
AU  - Maxwell-Horn AC
AD  - Departments of Pediatrics.
FAU - Roden, Dan M
AU  - Roden DM
AD  - Departments of Pediatrics.
AD  - Medicine, and.
AD  - Pharmacology, Vanderbilt University School of Medicine, Nashville, TN.
FAU - Van Driest, Sara L
AU  - Van Driest SL
AD  - Departments of Pediatrics.
AD  - Medicine, and.
LA  - eng
GR  - P50 HD103537/HD/NICHD NIH HHS/United States
GR  - T32 GM007569/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000445/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Dev Behav Pediatr
JT  - Journal of developmental and behavioral pediatrics : JDBP
JID - 8006933
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Cytochrome P-450 CYP2D6/genetics
MH  - Genotype
MH  - Humans
MH  - *Pediatrics
MH  - Pharmacogenetics
MH  - *Risperidone/adverse effects
PMC - PMC7995603
MID - NIHMS1630950
EDAT- 2021/03/25 06:00
MHDA- 2021/10/29 06:00
PMCR- 2022/04/01
CRDT- 2021/03/24 12:49
PHST- 2020/02/06 00:00 [received]
PHST- 2020/09/14 00:00 [accepted]
PHST- 2021/03/24 12:49 [entrez]
PHST- 2021/03/25 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2022/04/01 00:00 [pmc-release]
AID - 00004703-202104000-00005 [pii]
AID - 10.1097/DBP.0000000000000883 [doi]
PST - ppublish
SO  - J Dev Behav Pediatr. 2021 Apr 1;42(3):205-212. doi: 10.1097/DBP.0000000000000883.