What medications can cause hyperprolactinemia?

From the Guidelines

Medications that can cause hyperprolactinemia include antipsychotics, antidepressants, antiemetics, certain antihypertensives, opioids, and estrogens, with antipsychotics being the most common culprits, particularly first-generation agents like haloperidol, chlorpromazine, and fluphenazine, as well as second-generation antipsychotics such as risperidone, paliperidone, and amisulpride 1. The mechanism behind medication-induced hyperprolactinemia primarily involves blocking dopamine D2 receptors in the tuberoinfundibular pathway, as dopamine normally inhibits prolactin secretion from the pituitary gland. When this inhibition is removed, prolactin levels rise. Some of the key medications that can cause hyperprolactinemia are:

• Antipsychotics: first-generation agents like haloperidol, chlorpromazine, and fluphenazine, as well as second-generation antipsychotics such as risperidone, paliperidone, and amisulpride
• Antidepressants: especially selective serotonin reuptake inhibitors (SSRIs) like sertraline, fluoxetine, and paroxetine
• Antiemetics: metoclopramide, domperidone
• Certain antihypertensives: verapamil, methyldopa
• Opioids
• Estrogens The degree of hyperprolactinemia varies by medication, with antipsychotics typically causing more significant elevations than other drug classes. Symptoms may include:
• Galactorrhea
• Menstrual irregularities in women
• Decreased libido
• Erectile dysfunction in men Management often involves switching to an alternative medication with less impact on prolactin when possible, though sometimes the clinical benefits of continuing the current medication outweigh the risks of hyperprolactinemia 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. Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration

• Medications that can cause hyperprolactinemia include:
  • Risperidone (PO) 2
  • Chlorpromazine (PO) 3
• Hyperprolactinemia may lead to symptoms such as galactorrhea, amenorrhea, gynecomastia, and impotence.
• It is essential to monitor prolactin levels in patients taking these medications, especially those with a history of breast cancer or other conditions that may be affected by hyperprolactinemia.

From the Research

Medications that Cause Hyperprolactinemia

Medications are a common cause of hyperprolactinemia, and it is essential to differentiate this cause from pathologic causes, such as prolactinomas 4, 5. The following medications can cause hyperprolactinemia:

• Antipsychotic agents, particularly typical antipsychotics and some atypical antipsychotics like risperidone 4, 6, 7, 8
• Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and some tricyclics 6, 5
• Antihypertensive agents 4, 5
• Drugs that increase bowel motility, such as prokinetics 4, 6
• Opiates 6
• Estrogens 6
• Anti-androgens 6
• H2-receptor antagonists 6
• Anti-convulsants 6
• Cholinomimetics 6

Management of Medication-Induced Hyperprolactinemia

If a patient's hyperprolactinemia is suspected to be caused by a medication, the following steps can be taken:

• Stop the medication temporarily to determine if prolactin levels return to normal 4, 5
• Switch to a medication that does not cause hyperprolactinemia, in consultation with the patient's physician and/or psychiatrist 4, 5
• Perform an MRI or CT scan to rule out a structural lesion in the hypothalamic-pituitary area 4, 5
• If the patient's hyperprolactinemia is symptomatic, treatment strategies include switching to an alternative medication, using estrogen or testosterone replacement, or cautiously adding a dopamine agonist 4, 5