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CYP2D6 Phenotype Influences Aripiprazole Tolerability in Pediatric Patients with Mood Disorders

Sahar A Jallaq1,2, Mark Verba1,3, Jeffrey R Strawn4,5,6

  • 1Division of Research in Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Journal of Child and Adolescent Psychopharmacology
|August 27, 2020
PubMed

Insights

Pediatric patients with mood disorders on aripiprazole who are poor metabolizers (PMs) of CYP2D6 are more likely to discontinue treatment due to side effects. Adjusting aripiprazole doses based on CYP2D6 metabolizer status and other medications can improve treatment outcomes.

Area of Science:

  • Pharmacogenomics
  • Psychiatry

Background:

  • Aripiprazole is a widely used antipsychotic for mood disorders in pediatric patients.
  • CYP2D6 enzyme activity significantly influences aripiprazole metabolism and patient response.
  • Individual variability in CYP2D6 metabolizer status can affect drug tolerability and efficacy.

Purpose of the Study:

  • To investigate the association between CYP2D6 metabolizer status and aripiprazole tolerability in pediatric patients with mood disorders.
  • To determine if phenoconversion due to concomitant medications impacts aripiprazole discontinuation rates.
  • To explore the relationship between CYP2D6 phenotype and changes in body mass index.

Main Methods:

  • Retrospective review of 277 pediatric patients (≤18 years) with mood disorders treated with oral aripiprazole.
  • Analysis of CYP2D6 genotype and phenoconversion status, considering concomitant CYP2D6 inhibitors.
  • Multivariate regression and chi-square tests to assess associations between CYP2D6 status, side effects, and body mass index changes.

Main Results:

  • Poor metabolizers (PMs) with phenoconversion (pPMs) showed higher discontinuation rates due to side effects (67%) compared to other CYP2D6 groups.
  • Phenoconversion affected a significant portion of the cohort, altering effective metabolizer status.
  • CYP2D6 phenotype, duration of treatment, and number of concomitant CYP2D6 substrates were associated with BMI percentile change.

Conclusions:

  • Phenoconverted CYP2D6 metabolizer status is a significant factor in aripiprazole discontinuation among pediatric patients.
  • Personalized aripiprazole dosing strategies, considering CYP2D6 genotype and medication interactions, are crucial for optimizing treatment outcomes.
  • Further research into pharmacogenomic-guided dosing can enhance aripiprazole tolerability and effectiveness in pediatric mood disorder management.

Keywords:
CYP2D6antipsychoticsaripiprazolemood disorderspharmacogenetics

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