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Pharmacogenetic testing of CYP2D6 in patients with aripiprazole-related extrapyramidal symptoms: a case-control study

Anton A Subuh Surja1,2, Kristen K Reynolds3, Mark W Linder3

  • 1University of Louisville, Department of Psychiatry and Behavioral Sciences, MedCenter One Building, 501 E. Broadway, Suite 340, Louisville, KY, 40202, USA. rselma01@louisville.edu.

Personalized Medicine
|May 23, 2018
PubMed

Insights

Children with a dysfunctional CYP2D6 enzyme, affecting drug metabolism, experienced more extrapyramidal symptoms when taking aripiprazole. Genetic variations in CYP2D6 may increase the risk of adverse reactions in pediatric patients.

Area of Science:

  • Pharmacogenetics
  • Pediatric Pharmacology
  • Neuroscience

Background:

  • Aripiprazole is a widely used antipsychotic medication.
  • Its metabolism is significantly influenced by the cytochrome P450 2D6 (CYP2D6) enzyme.
  • CYP2D6 is highly polymorphic, leading to variations in drug metabolism among individuals.

Purpose of the Study:

  • To investigate the association between CYP2D6 genotype and the occurrence of extrapyramidal symptoms (EPS) in children treated with aripiprazole.
  • To identify potential genetic risk factors for aripiprazole-induced adverse drug reactions in a pediatric population.

Main Methods:

  • Genotyping of the CYP2D6 enzyme in pediatric patients who developed EPS on aripiprazole.
  • Comparison of CYP2D6 genotypes between a case group (with EPS) and a control group (without EPS).
  • Phenotyping of CYP2D6 metabolic activity based on genetic variations (intermediate and poor metabolizers).

Main Results:

  • All four children who developed EPS had a dysfunctional CYP2D6 enzyme (2 intermediate, 2 poor metabolizers).
  • In contrast, only two children in the control group exhibited these CYP2D6 metabolic phenotypes.
  • A higher prevalence of CYP2D6 abnormalities was observed in children experiencing aripiprazole-induced EPS.

Conclusions:

  • Children with CYP2D6 genetic variations, particularly intermediate or poor metabolizers, may be at an elevated risk for developing extrapyramidal symptoms from aripiprazole.
  • CYP2D6 genotyping could aid in personalized medicine approaches for aripiprazole treatment in children.
  • Further research is warranted to confirm these findings and establish clinical guidelines.

Keywords:
CYP2D6adverse drug reactionaripiprazolebipolar disorderextrapyramidal symptomsgene polymorphisms

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