From the FDA Drug Label
Hyperprolactinemia RISPERIDONE has been shown to elevate prolactin levels in children and adolescents as well as in adults [see WARNINGS AND PRECAUTIONS ( 5. 6)]. 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 Similarly, in placebo-controlled trials in children and adolescents (aged 10 to 17 years) with bipolar disorder, or adolescents (aged 13 to 17 years) with schizophrenia, 82 to 87% of patients who received RISPERIDONE had elevated levels of prolactin compared to 3 to 7% of patients on placebo. Increases were dose-dependent and generally greater in females than in males across indications. In clinical trials in 1885 children and adolescents, galactorrhea was reported in 0. 8% of RISPERIDONE-treated patients and gynecomastia was reported in 2.3% of RISPERIDONE-treated patients.
The dopamine pathway most likely involved when a patient with psychosis, started on Risperidone (risperidone), develops bilateral breast enlargement, also known as gynecomastia, is the tuberoinfundibular pathway. This pathway is involved in the regulation of prolactin secretion, and risperidone's ability to elevate prolactin levels is a known side effect of the medication 1. The elevation of prolactin levels can lead to gynecomastia, as well as other symptoms such as galactorrhea.
- Key points:
- Risperidone elevates prolactin levels
- Elevated prolactin levels can lead to gynecomastia
- The tuberoinfundibular pathway is involved in the regulation of prolactin secretion
- Risperidone's effect on this pathway is the likely cause of gynecomastia in patients taking the medication 1
From the Research
The correct answer is A. Tuberoinfundibular pathway, as risperidone blocks dopamine D2 receptors in this pathway, leading to hyperprolactinemia and gynecomastia, as supported by the most recent evidence from 2.
Pathophysiology of Gynecomastia
Risperidone, an atypical antipsychotic, can cause bilateral breast enlargement (gynecomastia) by blocking dopamine D2 receptors in the tuberoinfundibular pathway. This pathway normally allows dopamine to inhibit prolactin release from the anterior pituitary. When risperidone blocks these receptors, the inhibitory effect of dopamine is removed, resulting in hyperprolactinemia. Elevated prolactin levels stimulate breast tissue growth in both males and females, leading to gynecomastia.
Dopamine Pathways and Their Functions
The mesolimbic pathway is associated with positive symptoms of schizophrenia, the corticolimbic pathway with cognitive and negative symptoms, and the nigrostriatal pathway with movement disorders like extrapyramidal symptoms. Only the tuberoinfundibular pathway directly regulates prolactin secretion and is responsible for endocrine side effects like gynecomastia.
Clinical Evidence and Guidelines
According to the EAA clinical practice guidelines on gynecomastia evaluation and management 2, the presence of an underlying pathology should be considered in gynecomastia of adulthood, and a thorough diagnostic workup is warranted in such cases. The guidelines also recommend that the medical history should include information on the onset and duration of gynecomastia, sexual development and function, and administration or abuse of substances associated with gynecomastia.
Key Points
- Risperidone can cause gynecomastia by blocking dopamine D2 receptors in the tuberoinfundibular pathway.
- The tuberoinfundibular pathway is responsible for regulating prolactin secretion and is associated with endocrine side effects like gynecomastia.
- A thorough diagnostic workup is warranted in cases of gynecomastia of adulthood, as recommended by the EAA clinical practice guidelines 2.
- The mesolimbic, corticolimbic, and nigrostriatal pathways are associated with different symptoms and side effects, but only the tuberoinfundibular pathway is directly involved in prolactin regulation and gynecomastia.