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Recognition of impaired atomoxetine metabolism because of low CYP2D6 activity

Maureen A ter Laak1, Alphons H Temmink, Ankie Koeken

  • 1Department of Clinical Pharmacy, Amphia Hospital, Breda, The Netherlands. mtlaak@tsz.nl

Pediatric Neurology
|August 10, 2010
PubMed

Insights

Genetic testing for cytochrome P450 2D6 can identify children with attention deficit hyperactivity disorder who may not properly metabolize atomoxetine, preventing adverse effects and improving treatment outcomes.

Area of Science:

  • Pharmacogenomics
  • Neuroscience
  • Pediatric Medicine

Background:

  • Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children.
  • Atomoxetine is a commonly prescribed medication for ADHD.
  • Individual variability in drug metabolism can affect treatment efficacy and safety.

Purpose of the Study:

  • To investigate the role of cytochrome P450 (CYP) enzyme genetic variations in atomoxetine response in children with ADHD.
  • To identify potential genetic markers for predicting adverse effects and treatment outcomes with atomoxetine.

Main Methods:

  • Retrospective analysis of 100 children with ADHD treated with atomoxetine.
  • Neurologist selection of 10 children for CYP2D6 and CYP2C19 genotyping based on late response or adverse effects.
  • Analysis of genotype data in relation to clinical response and adverse events.

Main Results:

  • Eight out of 10 genotyped children had compromised CYP2D6 activity.
  • Four children with reduced CYP2D6 activity showed improved response after atomoxetine dose reduction.
  • Four children discontinued atomoxetine due to adverse effects, potentially linked to metabolism issues.

Conclusions:

  • Compromised atomoxetine metabolism, particularly via CYP2D6, can be identified through late response and adverse effects.
  • Physician awareness of specific adverse effect patterns and delayed response is crucial.
  • Prospective CYP2D6 genotyping may help optimize atomoxetine dosing and prevent early treatment cessation in children with ADHD.

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