From the Guidelines
Strattera (atomoxetine) works by increasing synaptic noradrenaline by binding to the norepinephrine transporter, thereby classified as a norepinephrine reuptake inhibitor, and also increases dopamine in the synapses within the prefrontal cortex. This mechanism of action is supported by a recent study published in 2022 1. The study explains that atomoxetine increases both noradrenaline and dopamine in the synapses within the prefrontal cortex, which helps improve attention, impulse control, and executive functioning.
Key Points about Strattera Mechanism
- Atomoxetine is orally administered and primarily metabolized through the cytochrome P450 2D6 (CYP2D6) pathway 1.
- It is approved in many countries to treat ADHD in children, adolescents, and adults 1.
- The medication is usually started at a lower dose and gradually increased to a target dose, with a maximum recommended dosage of 1.4 mg/kg/day or 100 mg/day, whichever is lower 1.
- Common side effects include nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence 1.
Important Considerations
- Atomoxetine may increase the risk of suicidal ideation in children and adolescents, and close monitoring is recommended, especially during the first few months of treatment or at times of dose change 1.
- Warnings also exist for preexisting cardiovascular diseases, significant cardiac abnormalities, emergent psychotic or manic symptoms, bipolar disorder, aggressive behavior or hostility, possible allergic reactions, effects on urine outflow and growth, and priapism in children, adolescents, and adults 1.
From the FDA Drug Label
- 1 Mechanism of Action The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter, as determined in ex vivo uptake and neurotransmitter depletion studies.
The mechanism of action of Straterra (atomoxetine) is thought to be related to the selective inhibition of the pre-synaptic norepinephrine transporter. However, the precise mechanism by which it produces its therapeutic effects in ADHD is unknown 2.
From the Research
Mechanism of Action
- The mechanism of action of atomoxetine is thought to be related to its selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex 3.
- Atomoxetine has a high affinity and selectivity for norepinephrine transporters, but little or no affinity for various neurotransmitter receptors 3.
- It has a demonstrated ability to selectively inhibit norepinephrine uptake in humans and animals, and studies have shown that it preferentially binds to areas of known high distribution of noradrenergic neurons, such as the fronto-cortical subsystem 3.
Pharmacokinetics
- Atomoxetine is rapidly absorbed, and demonstrates dose-proportional increases in plasma exposure 3.
- It undergoes extensive biotransformation, which is affected by poor metabolism by cytochrome P450 (CYP) 2D6 in a small percentage of the population; these patients have greater exposure to and slower elimination of atomoxetine than extensive metabolizers 3.
- Patients with hepatic insufficiency show an increase in atomoxetine exposure 3.
- CYP2D6 inhibitors, such as paroxetine, are associated with changes in atomoxetine pharmacokinetics similar to those observed among poor CYP2D6 metabolizers 3.
Efficacy
- Atomoxetine has been shown to be effective in the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults 3, 4, 5, 6.
- It has been demonstrated to be significantly more effective than placebo in reducing ADHD symptoms, and has been shown to be noninferior to immediate-release methylphenidate 3.
- Atomoxetine has also been shown to be effective in the long-term treatment of ADHD, with continued efficacy demonstrated in a noncomparative, 34-week extension phase 4, 5.