From the Guidelines
Clozapine is less likely to cause hyperprolactinemia compared to other antipsychotics. While most antipsychotic medications can elevate prolactin levels by blocking dopamine D2 receptors in the tuberoinfundibular pathway, clozapine has a relatively weak affinity for these receptors, resulting in minimal impact on prolactin secretion. According to a study published in 2021 1, antipsychotic polypharmacy, which may include clozapine, can lead to various side effects, including hyperprolactinemia, although the effects on this specific condition were noted to be reduced when combining aripiprazole with an antipsychotic that has a greater side-effect burden.
When hyperprolactinemia does occur with clozapine, it is typically mild and transient, often normalizing even with continued treatment. Patients on clozapine should still be monitored for symptoms of hyperprolactinemia such as:
- Galactorrhea
- Menstrual irregularities
- Sexual dysfunction
- Gynecomastia If these symptoms develop, checking serum prolactin levels is recommended. For persistent symptomatic hyperprolactinemia, options include:
- Dose reduction if clinically feasible
- Switching to another antipsychotic with lower prolactin-elevating potential like aripiprazole or quetiapine
- In some cases, adding aripiprazole (partial D2 agonist) at 5-15 mg daily as an adjunctive treatment to reduce prolactin levels while maintaining clozapine's therapeutic effect. The decision should be individualized based on the severity of symptoms, the importance of continuing clozapine therapy, and the patient's overall clinical picture.
From the FDA Drug Label
Clozapine causes little or no prolactin elevation The FDA drug label states that clozapine causes little or no prolactin elevation. Therefore, it is unlikely to cause hyperprolactinemia 2.
- Key points:
- Clozapine has minimal effect on prolactin levels
- It is not expected to cause significant hyperprolactinemia The information provided in the drug label suggests that clozapine is not likely to cause hyperprolactinemia 2.
From the Research
Clozapine and Hyperprolactinemia
- Clozapine is reported to lack the effect of inducing hyperprolactinemia, which is a common consequence of conventional antipsychotic therapy 3.
- A case study found that switching to clozapine therapy improved psychiatric status and corrected serum prolactin concentrations in a patient with hyperprolactinemia induced by conventional antipsychotics 3.
- Clozapine is considered a prolactin-sparing antipsychotic, meaning it has a minimal or no significant effect on prolactin levels 4, 5.
Hyperprolactinemia Induced by Antipsychotics
- Hyperprolactinemia is a common adverse effect of antipsychotic medication, occurring frequently with conventional antipsychotics and some atypical antipsychotics 4, 5.
- Symptoms of hyperprolactinemia include gynaecomastia, galactorrhoea, menstrual irregularities, infertility, sexual dysfunction, acne, and hirsutism 4, 5.
- Long-term consequences of antipsychotic-related hypogonadism may include premature bone loss in men and women, and there is conflicting data on the association with breast cancer in women 5.
Management of Hyperprolactinemia
- Management options for antipsychotic-induced hyperprolactinemia include reducing the dose of the offending antipsychotic, switching to a prolactin-sparing antipsychotic, or adding a dopamine receptor agonist such as bromocriptine or cabergoline 4, 5, 6, 7.
- Adding aripiprazole has been found to be effective in lowering prolactin concentrations in patients with schizophrenia and hyperprolactinemia 6.
- Other management options, such as metformin and herbal supplements, have limited evidence to support their use in antipsychotic-induced hyperprolactinemia 7.