Which antipsychotic is most commonly associated with increased prolactin secretion?

• A. Risperidone
• B. Clozapine
• C. Olanzapine
• D. Quetiapine

Answer: (A)

Dopamine normally keeps prolactin levels in check by acting on D2 receptors in the tuberoinfundibular pathway. When an antipsychotic blocks these receptors, this inhibitory effect is removed, leading to increased prolactin secretion. Among common atypical antipsychotics, one with particularly strong D2 antagonism and high receptor occupancy—including at the pituitary—tends to cause the most prolactin elevation. This produces effects like galactorrhea, amenorrhea, sexual dysfunction, and potential bone-density changes with long-term high prolactin.

Clozapine and olanzapine have weaker or more offset D2 blockade at the pituitary and more influence from serotonin antagonism, which tends to limit prolactin increases. Quetiapine also shows relatively low prolactin effects due to rapid dissociation from D2 receptors and lower occupancy. Therefore, the antipsychotic most associated with increased prolactin is the one with the strongest pituitary D2 blockade, risperidone.