What antidepressants increase dopamine?

From the Guidelines

Atomoxetine is an antidepressant that increases dopamine levels, particularly in the prefrontal cortex, by binding to the norepinephrine transporter and regulating dopamine reuptake 1.

Key Points

• Atomoxetine is classified as a norepinephrine reuptake inhibitor, but it also increases dopamine in the synapses within the prefrontal cortex.
• The medication is orally administered, with a maximum recommended dosage of 1.4 mg/kg/day or 100 mg/day, whichever is lower.
• Common adverse effects of atomoxetine include nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence.
• Special warnings exist for children being treated with atomoxetine, who should be monitored closely for suicidality, clinical worsening, and unusual changes of behavior.
• Atomoxetine is currently approved in many countries to treat ADHD in children, adolescents, and adults.

Mechanism of Action

Atomoxetine works by increasing synaptic noradrenaline and dopamine in the prefrontal cortex, where norepinephrine transporters are responsible for regulating dopamine reuptake 1.

Important Considerations

• Atomoxetine should be used with caution in patients with preexisting cardiovascular diseases or significant cardiac abnormalities, and in those with a history of emergent psychotic or manic symptoms, bipolar disorder, or aggressive behavior.
• The medication may interact with certain selective serotonin reuptake inhibitors, which can elevate serum atomoxetine levels.

From the Research

Antidepressants that Increase Dopamine

• Fluoxetine, a selective serotonin uptake inhibitor (SSRI), has been shown to increase dopamine extracellular levels in the prefrontal cortex 2
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) achieve faster antidepressant effects than SSRIs by elevating dopamine concentrations in the forebrain 3
• Drugs with antidepressant potential, such as fluoxetine, clomipramine, imipramine, desipramine, and (+/-) 8-OHDPAT, increase extracellular concentrations of dopamine in the rat prefrontal cortex 4

Mechanisms of Dopamine Increase

• Fluoxetine's increase in dopamine extracellular levels may be due to its ability to block 5-HT(2C) receptors 2
• SNRIs' increase in dopamine concentrations may contribute to their faster antidepressant effects compared to SSRIs 3
• The dopaminergic system may play a role in the antidepressant properties of certain drugs, including fluoxetine and SNRIs 5, 3, 4

Other Antidepressants and Dopamine

• Buspirone, an anxiolytic drug, increases dopamine both in the prefrontal cortex and in the nucleus accumbens 4
• Dopaminergic receptor agonists and antagonists, such as olanzapine, may exhibit antidepressant effects in patients with treatment-resistant depression 6