PMID- 30661084
OWN - NLM
STAT- MEDLINE
DCOM- 20200512
LR  - 20210109
IS  - 1530-0447 (Electronic)
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 85
IP  - 5
DP  - 2019 Apr
TI  - CYP2D6 genotype and adverse events to risperidone in children and adolescents.
PG  - 602-606
LID - 10.1038/s41390-019-0305-z [doi]
AB  - BACKGROUND: There are few and conflicting data on the role of cytochrome P450 2D6 
      (CYP2D6) polymorphisms in relation to risperidone adverse events (AEs) in 
      children. This study assessed the association between CYP2D6 metabolizer status 
      and risk for risperidone AEs in children. METHODS: Children </=18 years with at 
      least 4 weeks of risperidone exposure were identified using BioVU, a 
      de-identified DNA biobank linked to electronic health record data. The primary 
      outcome of this study was AEs. After DNA sequencing, individuals were classified 
      as CYP2D6 poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. RESULTS: 
      For analysis, the 257 individuals were grouped as poor/intermediate metabolizers 
      (n = 33, 13%) and normal/ultrarapid metabolizers (n = 224, 87%). AEs were more 
      common in poor/intermediate vs. normal/ultrarapid metabolizers (15/33, 46% vs. 
      61/224, 27%, P = 0.04). In multivariate analysis adjusting for age, sex, race, 
      and initial dose, poor/intermediate metabolizers had increased AE risk (adjusted 
      odds ratio 2.4, 95% confidence interval 1.1-5.1, P = 0.03). CONCLUSION: Children 
      with CYP2D6 poor or intermediate metabolizer phenotypes are at greater risk for 
      risperidone AEs. Pre-prescription genotyping could identify this high-risk subset 
      for an alternate therapy, risperidone dose reduction, and/or increased monitoring 
      for AEs.
FAU - Oshikoya, Kazeem A
AU  - Oshikoya KA
AD  - Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, 
      USA.
FAU - Neely, Katelyn M
AU  - Neely KM
AD  - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 
      TN, USA.
FAU - Carroll, Robert J
AU  - Carroll RJ
AD  - Department of Biomedical Informatics, Vanderbilt University School of Medicine, 
      Nashville, TN, USA.
FAU - Aka, Ida T
AU  - Aka IT
AD  - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 
      TN, USA.
FAU - Maxwell-Horn, Angela C
AU  - Maxwell-Horn AC
AD  - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 
      TN, USA.
FAU - Roden, Dan M
AU  - Roden DM
AD  - Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, 
      USA.
FAU - Van Driest, Sara L
AU  - Van Driest SL
AD  - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 
      TN, USA. sara.van.driest@vumc.org.
LA  - eng
GR  - KL2 TR000446/TR/NCATS 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
PT  - Research Support, Non-U.S. Gov't
DEP - 20190119
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Adolescent
MH  - Alleles
MH  - Child
MH  - Cytochrome P-450 CYP2D6/*genetics
MH  - Electronic Health Records
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - *Pharmacogenetics
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Retrospective Studies
MH  - Risk
MH  - Risperidone/*adverse effects
MH  - Treatment Outcome
PMC - PMC6435416
MID - NIHMS1518655
COIS- Disclosures: Dr. Van Driest has been an invited speaker to Merck. Dr. Oshikoya, 
      Dr. Neely, Dr. Carroll, Ms. Aka, Dr. Maxwell-Horn, and Dr. Roden declare no 
      conflicts of interest.
EDAT- 2019/01/21 06:00
MHDA- 2020/05/13 06:00
PMCR- 2019/07/19
CRDT- 2019/01/21 06:00
PHST- 2018/11/06 00:00 [received]
PHST- 2019/01/13 00:00 [accepted]
PHST- 2018/11/11 00:00 [revised]
PHST- 2019/01/21 06:00 [pubmed]
PHST- 2020/05/13 06:00 [medline]
PHST- 2019/01/21 06:00 [entrez]
PHST- 2019/07/19 00:00 [pmc-release]
AID - 10.1038/s41390-019-0305-z [pii]
AID - 10.1038/s41390-019-0305-z [doi]
PST - ppublish
SO  - Pediatr Res. 2019 Apr;85(5):602-606. doi: 10.1038/s41390-019-0305-z. Epub 2019 
      Jan 19.