What is the effect of Invega (paliperidone) on prolactin levels?

From the Guidelines

Invega (paliperidone) significantly increases prolactin levels, with studies showing elevations of 2-4 times above normal ranges in many patients. Women typically experience higher increases than men, with levels sometimes reaching 40-100 ng/mL in women and 20-50 ng/mL in men (normal ranges are approximately 2-25 ng/mL for women and 2-15 ng/mL for men) 1. These elevations usually occur within the first few weeks of treatment and can persist throughout therapy. The prolactin increase is dose-dependent, with higher doses causing greater elevations. This effect occurs because paliperidone blocks dopamine D2 receptors in the tuberoinfundibular pathway of the brain, removing dopamine's inhibitory effect on prolactin secretion from the pituitary gland.

Key Points to Consider

• Patients should be monitored for symptoms of hyperprolactinemia such as menstrual irregularities, sexual dysfunction, gynecomastia, or galactorrhea 1.
• If problematic symptoms develop, dose reduction or switching to an antipsychotic with less impact on prolactin levels might be necessary 1.
• The management of prolactinomas involves dopamine agonists as first-line therapy to reduce serum prolactin concentrations and induce tumour shrinkage, with cabergoline being the dopamine agonist of choice given its superior effectiveness and lower adverse effect profile 1.
• In cases where dopamine agonist resistance or intolerance occurs, neurosurgical intervention should be considered, especially if vision deteriorates or does not improve on medical therapy 1.

Monitoring and Management

• Regular monitoring of prolactin levels and assessment of symptoms is crucial in managing patients on Invega (paliperidone) 1.
• The use of dopamine agonists, such as cabergoline, can effectively reduce prolactin levels and induce tumour shrinkage in patients with prolactinomas 1.
• In exceptional cases where other treatment modalities are not available or have been exhausted, radiotherapy may be considered to control tumour growth, although normalization of prolactin levels is a secondary objective 1.

From the FDA Drug Label

Like other drugs that antagonize dopamine D2 receptors, paliperidone elevates prolactin levels and the elevation persists during chronic administration. Paliperidone has a prolactin-elevating effect similar to that seen with risperidone, a drug that is associated with higher levels of prolactin than other antipsychotic drugs

• Prolactin levels are elevated by paliperidone, similar to risperidone, due to its dopamine D2 receptor antagonism.
• This elevation persists during chronic administration.
• The prolactin-elevating effect of paliperidone may lead to hyperprolactinemia, which can cause symptoms such as galactorrhea, amenorrhea, gynecomastia, and impotence.
• Long-standing hyperprolactinemia may also lead to decreased bone density in both female and male subjects 2.

From the Research

Effect of Invega (Paliperidone) on Prolactin Levels

• Invega (paliperidone) is a second-generation antipsychotic that can increase prolactin secretion, leading to hyperprolactinemia 3.
• Hyperprolactinemia can have short- and long-term consequences, including menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer 3.
• The risk of hyperprolactinemia can be minimized by using the lowest effective dose of the antipsychotic agent 3.
• If the effects of prolactin are evident, the drug can be changed to another agent that is less likely to affect prolactin levels; alternatively, a dopamine agonist may be added, although this may compromise antipsychotic efficacy 3.
• Risperidone, a related antipsychotic, has been shown to cause clinically significant hyperprolactinemia in patients, which can be alleviated by adding dopamine agonists such as bromocriptine or cabergoline 4.
• Cabergoline has been shown to be superior to bromocriptine in affecting atherogenic dyslipidaemia, insulin sensitivity, and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients 5.
• Antipsychotic-induced hyperprolactinemia is a concern in aging populations, and methods of prevention include using antipsychotic medication sparingly, monitoring serum levels, and regularly measuring prolactin levels 6.
• Risperidone has been shown to increase prolactin levels in adolescents, with clinical consequences such as gynecomastia and/or galactorrhea 7.