Personalizing Atomoxetine Dosing in Children with ADHD: What Can We
Learn from Current Supporting Evidence
Abstract
Atomoxetine is the first non-stimulant medication approved by the US
Food and Drug Administration for the treatment of attention
deficit/hyperactivity disorder (ADHD). It can significantly improve ADHD
symptoms, with good efficacy and tolerability. However, its efficacy was
not consistent among all patients, especially for pediatric population.
Due to marked heterogeneity in treatment response, a precision therapy
should be developed and evaluated to guide treatment planning at the
individual level. We have gained a better understanding of the
pharmacokinetic profile. This review summarized some factors affecting
peak concentrations of atomoxetine, including food, CYP2D6 and CYP2C19
phenotypes, and drug-drug interactions. The association between response
and genetic polymorphisms of genes encoding the pharmacological targets
such as norepinephrine transporter (NET/SLC6A2) and dopamine β
hydroxylase (DBH) was also discussed. Based on the well-developed and
validated assays for monitoring plasma concentrations of atomoxetine,
the therapeutic reference range in pediatric patients with ADHD proposed
by several studies was summarized. However, supporting evidence on the
relationship between systemic atomoxetine exposure levels and clinical
response is far from sufficient. We have to create evidence to
characterize clearly the dose-exposure relationship, to establish
clinically relevant metric for systemic exposure, to define a
therapeutic exposure range, and to provide a dose-adaptation strategy
before implementing personalized dosing for atomoxetine in children with
ADHD. Personalizing atomoxetine dosage may be even more complex than we
anticipated, but we can be optimistic about the future based on the
remarkable advances in understanding the nature and causes of ADHD, as
well as environmental stressors.