The Mechanism, Clinical Efficacy, Safety, and Dosage Regimen of Atomoxetine for ADHD Therapy in Children: A Narrative Review

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.

Effects of Atomoxetine on Motor and Cognitive Behaviors and Brain Electrophysiological Activity of Dopamine Transporter Knockout Rats

“…In ADHD, changes in DA and NE are thought to play a crucial role in the pathology of the disorder [ 10 , 11 , 12 ], although the contribution of serotonin system to at least some behavioral manifestations cannot be excluded [ 13 , 14 ]. One of the approved medications with proven clinical efficacy in reducing ADHD symptoms is atomoxetine (ATX, atomoxetine, LY139603) [ 15 , 16 , 17 ]. ATX is a selective norepinephrine transporter (NET) inhibitor that increases extracellular levels of NE, as well as DA, in NET-enriched areas, such as the PFC, the occipital cortex, the hypothalamus, the hippocampus and the cerebellum [ 18 , 19 , 20 , 21 ].…”

The use of attention-deficit hyperactivity disorder medications in cardiac disease

“…Dexamfetamine based medications have the added action of increased release of dopamine. Atomoxetine is a selective norepinephrine reuptake inhibitor (SNRI), however, it also increases dopaminergic transmission in the pre-frontal cortex as norepinephrine reuptake is linked to dopamine inactivation ( Fu et al, 2022 ). Clonidine and guanfacine are centrally acting alpha-2-agonists which decrease sympathetic outflow from the central nervous system.…”

Convergence mechanism of mindfulness intervention in treating attention deficit hyperactivity disorder: Clues from current evidence

“…Several limitations in current research are worth mentioning: (1) Discussions on mindfulness intervention in ADHD treatment are still focused on clinical indexes, such as its therapeutic effect[ 82 ], which has been adequately shown to be effective, accessible, and safe[ 7 ]. However, few studies have deeply explored the underlying neurobiological mechanisms[ 83 ].…”