Can Strattera (atomoxetine) increase dopamine levels?

Atomoxetine's Effect on Dopamine Levels

Atomoxetine (Strattera) primarily increases dopamine levels in the prefrontal cortex only, while it increases norepinephrine throughout the brain. 1, 2

Mechanism of Action

Atomoxetine works through a distinct mechanism compared to stimulant medications:

• It is a selective norepinephrine reuptake inhibitor that blocks the presynaptic norepinephrine transporter (NET) 2, 3
• This blockade prevents the reuptake of norepinephrine throughout various brain regions 1
• Unlike stimulants, atomoxetine has a region-specific effect on dopamine:
  • Increases dopamine specifically in the prefrontal cortex 1, 3
  • Does not increase dopamine in other regions such as the nucleus accumbens, striatum, lateral hypothalamus, or occipital cortex 1

Regional Specificity of Dopamine Effects

Research using in vivo microdialysis in rats has demonstrated this regional specificity:

• Atomoxetine robustly increased norepinephrine in multiple brain regions (prefrontal cortex, occipital cortex, lateral hypothalamus, dorsal hippocampus, and cerebellum) 1
• However, dopamine increases were only observed in the prefrontal cortex 1
• This contrasts with stimulants like methylphenidate, which increase dopamine in reward-related brain regions like the nucleus accumbens 1

Clinical Implications

The selective increase of dopamine in the prefrontal cortex has important clinical implications:

• May improve executive functions controlled by the prefrontal cortex (planning, impulse control) that are impaired in ADHD 4, 2
• Contributes to its effectiveness in ADHD treatment without producing euphoria or having abuse potential 2, 5
• Makes atomoxetine particularly suitable for patients with:
  • History of substance abuse concerns 2, 5
  • Comorbid anxiety or tics 2
  • Need for 24-hour symptom control 2

Additional Neurochemical Effects

Beyond its effects on catecholamines, atomoxetine also:

• Increases acetylcholine levels in cortical brain regions 6
• This procholinergic effect may contribute to its cognitive-enhancing properties 6
• The increase in cortical acetylcholine appears to be dependent on norepinephrine alpha-1 and/or dopamine D1 receptor activation 6

Important Considerations

• Atomoxetine's metabolism is affected by CYP2D6 genetic variations, with approximately 7% of the population being poor metabolizers who may experience higher plasma levels 2, 7
• Unlike stimulants, atomoxetine is not a controlled substance and has negligible abuse potential 2, 5
• It can be administered as a once-daily dose or split into two evenly divided doses 2, 5

In summary, atomoxetine does increase dopamine, but in a regionally selective manner that is limited to the prefrontal cortex, which contributes to its therapeutic effects in ADHD without the abuse potential associated with stimulants.