Which antipsychotics are prolactin-sparing?

• A. Haloperidol, fluphenazine
• B. Risperidone, paliperidone
• C. Clozapine, quetiapine, aripiprazole
• D. Olanzapine, ziprasidone

Answer: (C)

Dopamine acting on D2 receptors in the tuberoinfundibular pathway normally suppresses prolactin release. Antipsychotics that strongly block these D2 receptors tend to raise prolactin, while those with weak D2 blockade or with partial agonism at D2 have little or even lowering effect on prolactin.

Clozapine and quetiapine have low D2 occupancy or rapid dissociation from the receptor, so they do not significantly elevate prolactin. Aripiprazole is a partial agonist at D2, which can maintain dopaminergic tone in that pathway and may reduce prolactin levels compared with full antagonists. For that reason, they are considered prolactin-sparing.

In contrast, drugs like haloperidol and fluphenazine are strong D2 antagonists and commonly cause hyperprolactinemia. Risperidone and paliperidone also tend to increase prolactin due to robust D2 blockade. Olanzapine and ziprasidone generally have lower prolactin risk, but the combination most consistently described as prolactin-sparing includes clozapine, quetiapine, and aripiprazole.