Role of the norepinephrine transporter polymorphisms in atomoxetine treatment: From response to side effects in children with ADHD

J Psychopharmacol. 2022 Jun;36(6):715-722. doi: 10.1177/02698811211015245. Epub 2021 May 4.


Objective: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter (NET/SLC6A2), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD.

Method: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at -80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR).

Results: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity.

Conclusion: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.

Keywords: ADHD; Children; NET; atomoxetine; treatment.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / adverse effects
  • Atomoxetine Hydrochloride* / adverse effects
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Attention Deficit Disorder with Hyperactivity* / genetics
  • Central Nervous System Stimulants* / therapeutic use
  • Child
  • Humans
  • Norepinephrine Plasma Membrane Transport Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Treatment Outcome


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Norepinephrine Plasma Membrane Transport Proteins
  • Atomoxetine Hydrochloride