To the Editor: Hyperprolactinemia is a well-recognized complication of treatment with antipsychotics, causing multiple endocrine and sexual side effects, including the risk for osteoporosis and possibly breast cancer (1). We report a case of successful treatment of risperidone-induced hyperprolactinemia by the partial dopamine agonist aripiprazole.

Aripiprazole lowers serum prolactin below placebo when it is used as a single agent (3). To our knowledge, this is the first case report of aripiprazole used in combination with another antipsychotic expressly to treat symptomatic hyperprolactinemia. Risperidone causes more marked elevations in prolactin than other atypical antipsychotics because it does not fully cross the blood-brain barrier (4). Dopamine D₂ receptor occupancy is therefore higher at the level of the pituitary than in the striatum. Aripiprazole has a greater affinity for the D₂ receptor than risperidone, with central D₂ receptor occupancy around 90% at a dose of 15 mg/day (5). The partial agonist property of this compound means that in the presence of dopamine hypoactivity, as induced by risperidone, aripiprazole will function as a dopamine agonist with roughly 30% intrinsic activity at postsynaptic receptors (5), restoring tonic inhibition to anterior pituitary lactotrophs. Spontaneous prolactin decline in this case would be unlikely because the time since risperidone exposure was short. However, normalization after longer-term treatment (1 year) has been reported (6).

It may be advantageous to avoid the use of directly acting dopaminergic agents in psychotic patients because of the risk for worsening psychosis. Whether this risk is really any lower for aripiprazole when combined with a direct D₂ receptor antagonist is not clear and would need to be answered in a controlled trial.