Does UzedY raise prolactin levels?

Does UZEDY Raise Prolactin?

Yes, UZEDY (risperidone extended-release injectable suspension) raises prolactin levels, as risperidone is one of the atypical antipsychotics most strongly associated with hyperprolactinemia, comparable to conventional antipsychotics in its prolactin-elevating effects. 1, 2

Mechanism of Prolactin Elevation

• Risperidone, the active ingredient in UZEDY, causes hyperprolactinemia by blocking dopamine D2 receptors in the tuberoinfundibular pathway, which normally inhibits prolactin secretion from the anterior pituitary 2
• Unlike other atypical antipsychotics such as clozapine, olanzapine, quetiapine, and ziprasidone that spare dopamine blockade in this pathway, risperidone does not demonstrate this selectivity 2
• High doses of risperidone (>6 mg/day) increase prolactin levels to ranges associated with sexual dysfunction in non-psychiatric patients 2

Clinical Significance and Monitoring

• Women are more sensitive than men to the hyperprolactinemic effects of risperidone 1
• In women, hyperprolactinemia manifests as amenorrhea/oligomenorrhea (45% of cases), galactorrhea, anovulation, loss of libido, occasional hirsutism, and increased long-term risk of osteoporosis 3, 2
• In men, symptoms include impotence, decreased libido, erectile dysfunction, hypospermatogenesis, and gynecomastia 4, 2

Distinguishing Medication-Induced from Pathologic Hyperprolactinemia

• Confirm the prolactin sample was taken in the morning while resting to ensure accurate measurement 3
• Rule out structural lesions in the hypothalamic/pituitary area through MRI or CT imaging if prolactin elevation is significant 5
• Consider temporarily stopping the medication (in consultation with psychiatry) to determine if prolactin levels normalize, confirming medication as the cause 5
• Exclude other causes including primary hypothyroidism, pregnancy, renal or hepatic disease, and assess for macroprolactinemia (present in 10-40% of hyperprolactinemia cases) 3, 4
• Be aware of the "high-dose hook effect" which can cause falsely low prolactin readings in cases of very high concentrations (occurs in ~5% of macroprolactinomas) 3, 4

Management Strategies

• Switching to an alternative atypical antipsychotic that does not elevate prolactin (clozapine, olanzapine, quetiapine, ziprasidone) is the preferred approach when clinically feasible 1, 2
• Gradual discontinuation of risperidone combined with initiation of olanzapine or clozapine can reverse risperidone-induced hyperprolactinemia 1
• If switching is not possible, consider estrogen or testosterone replacement therapy to prevent osteoporosis and maintain adequate sex steroid impregnation 6, 5
• Cautiously adding a dopamine agonist (such as cabergoline) is rarely used and potentially dangerous in medication-induced hyperprolactinemia, and should only be considered after confirming absence of pituitary adenoma 6, 5

Important Caveats

• Do not dismiss mild hyperprolactinemia without proper evaluation, as even mild elevations can cause significant menstrual disturbances and other symptoms 3
• For drug-induced hyperprolactinemia where the causative medication cannot be withdrawn, it is often pointless and possibly dangerous to administer dopamine agonists without first excluding structural pituitary lesions 6
• Monitor for long-term complications including osteoporosis risk, particularly in women with chronic amenorrhea from sustained hyperprolactinemia 2