Do any of these medications cause hyperprolactinemia (elevated prolactin levels)?

From the Guidelines

Medications are a common cause of hyperprolactinemia, particularly those that antagonize inhibitory dopaminergic tone, as reported in a 2024 consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1.

Medications Known to Cause Hyperprolactinemia

• Antipsychotics, especially first-generation agents like haloperidol and chlorpromazine, as well as some second-generation antipsychotics such as risperidone and paliperidone, are known to cause hyperprolactinemia 1.
• Certain antidepressants, including selective serotonin reuptake inhibitors (SSRIs) like sertraline and fluoxetine, can also elevate prolactin levels 1.
• Other medications that may cause hyperprolactinemia include metoclopramide, domperidone, verapamil, methyldopa, and estrogens, which typically cause hyperprolactinemia by blocking dopamine receptors in the pituitary gland or by interfering with dopamine production or release 1.

Mechanism of Action

These medications cause hyperprolactinemia by blocking dopamine receptors in the pituitary gland or by interfering with dopamine production or release, leading to an increase in prolactin levels, as dopamine normally inhibits prolactin secretion 1.

Clinical Considerations

If a patient develops symptoms of hyperprolactinemia, such as galactorrhea, menstrual irregularities, or sexual dysfunction, while taking these medications, their healthcare provider may consider switching to an alternative medication with less impact on prolactin levels, as recommended by the Guideline Development Group (GDG) 1.

From the FDA Drug Label

As with other drugs that antagonize dopamine D2 receptors, RISPERIDONE elevates prolactin levels and the elevation persists during chronic administration. RISPERIDONE is associated with higher levels of prolactin elevation than other antipsychotic agents. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. RISPERIDONE has been shown to elevate prolactin levels in children and adolescents as well as in adults In doubleblind, placebo-controlled studies of up to 8 weeks duration in children and adolescents (aged 5 to 17 years) with autistic disorder or psychiatric disorders other than autistic disorder, schizophrenia, or bipolar mania, 49% of patients who received RISPERIDONE had elevated prolactin levels compared to 2% of patients who received placebo Metoclopramide elevates prolactin levels and the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of metoclopramide is contemplated in a patient with previously detected breast cancer Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, the clinical significance of elevated serum prolactin levels is unknown for most patients.

Hyperprolactinemia is a potential side effect of both RISPERIDONE and metoclopramide.

• RISPERIDONE has been shown to elevate prolactin levels in children and adolescents as well as in adults.
• Metoclopramide also elevates prolactin levels and the elevation persists during chronic administration. Both drugs may cause galactorrhea, amenorrhea, gynecomastia, and impotence due to hyperprolactinemia. The clinical significance of elevated serum prolactin levels is unknown for most patients. It is essential to monitor prolactin levels and be aware of the potential risks associated with these medications. 2 2 3

From the Research

Medications that Cause Hyperprolactinemia

• Antipsychotic agents are the most common medications to cause hyperprolactinemia 4, 5, 6, 7, 8
• Some atypical antipsychotics, such as risperidone and paliperidone, are more likely to induce hyperprolactinemia than others 6, 8
• Antidepressants, including selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAO-I), and some tricyclics, can cause hyperprolactinemia 5, 6, 7
• Other medications that can cause hyperprolactinemia include:
  • Antihypertensive agents 5, 7
  • Prokinetics 6
  • Opiates 6
  • Estrogens 6
  • Anti-androgens 6
  • H2-receptor antagonists 6
  • Anti-convulsivants 6
  • Cholinomimetics 6

Management of Medication-Induced Hyperprolactinemia

• Stopping the medication temporarily to determine if prolactin levels return to normal 5, 7
• Switching to a medication that does not cause hyperprolactinemia 5, 7
• Using estrogen or testosterone replacement therapy 5, 7
• Cautiously adding a dopamine agonist 4, 5, 7
• Using the lowest effective dose of the antipsychotic agent to minimize the risk of hyperprolactinemia 8