Abstract
Atomoxetine, a selective norepinephrine (NE) reuptake inhibitor, was approved for attention deficit/hyperactivity disorder (ADHD) treatment in children, adolescents and adults. We searched the database PubMed/MEDLINE (2000 to October 1, 2021). Only publications in English were considered. Atomoxetine inhibits the presynaptic norepinephrine transporter (NET), preventing the reuptake of NE throughout the brain along with inhibiting the reuptake of dopamine in specific brain regions such as the prefrontal cortex (PFC). The novel mechanism of atomoxetine also includes several new brain imaging studies and animal model studies. It is mainly metabolized by the highly polymorphic drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6). Atomoxetine is effective and generally well tolerated. ADHD is often accompanied by multiple comorbidities. A series of studies have been published suggesting that atomoxetine is effective in the treatment of ADHD symptoms for children with various types of comorbidity. In some cases, it is possible that atomoxetine may have a positive influence on the symptoms of comorbidities. Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses, and has a negligible risk of abuse or misuse. The latest guideline updated that clinical dose selection of atomoxetine was recommended based on both CYP2D6 genotype and the peak concentration. To have a more comprehensive understanding of atomoxetine, this review sets the focus on the mechanism, clinical efficacy and dosage regimen in detail, and also touches on those studies regarding adverse reactions of atomoxetine.
Highlights
attention deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder commonly diagnosed in children and adolescents
The results indicated that atomoxetine was associated with a beneficial effect on tic severity, as atomoxetine treatment resulted in a significantly greater improvement than placebo (−0.7 vs. −0.1; p = 0.002) in the Clinical Global Impressions Tic/Neurologic Severity (CGI-Tic/Neuro-S) Scale scores, and both atomoxetine and placebo groups achieved significant improvements from baseline in tic severity assessed by the Yale Global Tic Severity Scale total score (YGTSS, primary measure of tic severity; −5.5 vs. −3.0) and the Tic Symptom SelfReport total score (TSSR; −4.7 vs. −2.9)
A study in Italy observed that the average heart rate in children with ADHD increased by 2.93 beats /min after 6 months of atomoxetine treatment compared with the baseline value, with a statistically significant difference (p < 0.001), while there was no statistically significant difference between the heart rate at 12th and 24th month compared with the baseline value (p > 0.05)
Summary
ADHD is a neuropsychiatric disorder commonly diagnosed in children and adolescents. It affects their learning, emotion, cognition, and social behavior to varying degrees [1, 2]. In contrast to European and North American guidelines, the 2014 Japanese clinical guidelines and the 2015 Chinese guideline recommend both non-stimulants and stimulants as the first-line pharmacological treatment for children and adolescents with ADHD. Atomoxetine is the first non-stimulant medication which was approved by the US Food and Drug Administration (FDA) to treat ADHD in late 2002 [25], and typically is prescribed to children who cannot tolerate or do not respond to stimulants [26]. It generally takes 2– 4 weeks for full impact on symptoms to be observed [27].
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