What is the antidepressant least likely to cause hyperprolactinemia (elevated prolactin levels)?

Antidepressants Least Likely to Cause Hyperprolactinemia

Bupropion is the antidepressant least likely to cause hyperprolactinemia, as it has no significant effect on serotonin reuptake and works primarily through dopaminergic and noradrenergic mechanisms.

Mechanism of Antidepressant-Induced Hyperprolactinemia

Hyperprolactinemia from antidepressants occurs primarily through serotonergic mechanisms:

• Serotonin stimulates prolactin release by inhibiting dopamine, which normally suppresses prolactin secretion
• Antidepressants with strong serotoninergic activity are more likely to cause hyperprolactinemia 1
• Classes of antidepressants that can cause hyperprolactinemia include:
  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Monoamine Oxidase Inhibitors (MAO-Is)
  • Some tricyclic antidepressants with serotonergic properties 1

Evidence for Specific Antidepressants

High Risk for Hyperprolactinemia

• SSRIs like fluoxetine can cause significant prolactin elevation and galactorrhea 2
• Sertraline has been documented to cause hyperprolactinemia with prolactin levels as high as 241 ng/mL 3
• Duloxetine (SNRI) can cause substantial hyperprolactinemia with levels up to 205 ng/mL 3

Lower Risk for Hyperprolactinemia

• Mirtazapine has been used as an alternative to sertraline to avoid hyperprolactinemia 3
• Bupropion has minimal serotonergic activity and works primarily on dopamine and norepinephrine pathways, making it least likely to cause hyperprolactinemia

Management of Antidepressant-Induced Hyperprolactinemia

If hyperprolactinemia occurs with an antidepressant:

1. Consider switching to an antidepressant less likely to cause hyperprolactinemia (e.g., bupropion or mirtazapine)
2. Aripiprazole (2.5-5mg daily) can be added as an adjunctive treatment to reduce prolactin levels while maintaining antidepressant therapy 3
3. Monitor prolactin levels to ensure normalization after intervention

Clinical Implications of Hyperprolactinemia

Symptoms of hyperprolactinemia that should prompt evaluation include:

• Galactorrhea (milk discharge)
• Menstrual irregularities in women
• Sexual dysfunction
• Infertility
• Decreased bone mineral density with long-term elevation 4

Monitoring Recommendations

For patients on antidepressants with risk of hyperprolactinemia:

• Check baseline prolactin levels before starting treatment in high-risk patients
• Monitor for clinical symptoms of hyperprolactinemia
• If symptoms develop, measure serum prolactin levels
• Normal reference ranges for serum prolactin:
  • Non-pregnant females: 3.0-30.0 ng/mL
  • Males: typically lower than females 5

Pitfalls to Avoid

• Failing to recognize that antidepressant-induced hyperprolactinemia is a medication side effect rather than a pituitary disorder
• Not considering medication-induced hyperprolactinemia in the differential diagnosis of elevated prolactin levels
• Ordering unnecessary imaging studies before ruling out medication effects 6
• Not distinguishing between transient and persistent hyperprolactinemia from antidepressants

When evaluating a patient with hyperprolactinemia who is on an antidepressant, consider temporarily discontinuing the medication (in consultation with the prescribing physician) to determine if prolactin levels normalize, or switch to an antidepressant less likely to cause this side effect 6.