From the Guidelines
Strattera (Atomoxetine) primarily affects the norepinephrine pathway, but it also has an indirect impact on the dopamine pathway, particularly in the prefrontal cortex, where it increases both noradrenaline and dopamine in the synapses. This is because, in the prefrontal cortex, norepinephrine transporters are responsible for the regulation of dopamine reuptake due to the scarcity of dopamine transporters in this region 1.
Key Differences and Mechanisms
- Strattera (Atomoxetine) is classified as a norepinephrine reuptake inhibitor, which means it works by binding to the norepinephrine transporter and increasing synaptic noradrenaline.
- The increase in noradrenaline levels improves attention and reduces impulsivity in individuals with ADHD.
- Unlike stimulants that directly affect the dopamine pathway, Strattera's primary mechanism is through the norepinephrine pathway, but it indirectly influences dopamine levels in certain areas of the brain, such as the prefrontal cortex.
- This dual effect on both norepinephrine and dopamine contributes to its therapeutic benefits in managing ADHD symptoms.
Clinical Considerations
- Strattera is orally administered and primarily metabolized through the cytochrome P450 2D6 (CYP2D6) pathway, which is important for considering potential drug interactions, especially with selective serotonin reuptake inhibitors that can elevate serum atomoxetine levels 1.
- The medication is approved for treating ADHD in children, adolescents, and adults, with specific dosing recommendations that include a maximum of 1.4 mg/kg/day or 100 mg/day, whichever is lower.
- Monitoring for suicidality, clinical worsening, and unusual changes in behavior is crucial, especially during the initial treatment phases or when adjusting the dose, as analyses have shown a greater risk of suicidal ideation in children and adolescents treated with atomoxetine 1.
From the Research
Mechanism of Action
- Strattera (Atomoxetine) is a selective norepinephrine reuptake inhibitor, which means it works by increasing the levels of norepinephrine in the brain 2, 3, 4, 5.
- The dopamine pathway, on the other hand, is involved in the transmission of dopamine, a different neurotransmitter, in the brain.
- Stimulants, such as methylphenidate and amphetamine, work by increasing the levels of dopamine and norepinephrine in the brain, whereas atomoxetine only increases norepinephrine levels 6.
Comparison of Strattera and Dopamine Pathway
- Strattera (Atomoxetine) is less efficacious than stimulants, which work on the dopamine pathway, but it is a useful option for patients who are at risk of substance abuse or who do not wish to take a controlled substance 2, 6, 4.
- Atomoxetine has a different mechanism of action compared to stimulants, which makes it a valuable treatment option for patients who do not respond to stimulants or who experience adverse effects 3, 4, 5.
- The efficacy of atomoxetine does not appear to be affected by the presence of co-morbid disorders, and symptoms of co-morbid disorders are not affected or are improved by atomoxetine administration 2, 4, 5.
Key Differences
- Strattera (Atomoxetine) is a non-stimulant medication, whereas stimulants, such as methylphenidate and amphetamine, work on the dopamine pathway and have a higher potential for abuse and dependence 2, 3, 6, 4, 5.
- Atomoxetine has a slower onset of action compared to stimulants, but it can provide long-term, consistent symptom relief and functional improvement for adults with ADHD 4, 5.