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To investigate the plasma levels of prolactin during treatment with aripiprazole and their relationship to extrapyramidal symptoms (EPS), the levels of prolactin were measured and episodes of EPS were reviewed in 129 inpatients treated with aripiprazole or olanzapine. The mean level of prolactin in the aripiprazole group was significantly lower than that in the olanzapine group (male: 2.5 vs. 23.5; female: 5.8 vs. 38.4 ng/mL, p < 0.01). In the male aripiprazole subjects, a significant negative correlation between prolactin levels and the dosage was found (p < 0.01) and, at some (but not all) dosages, extrapyramidal symptoms occurred in the subjects with the lowest prolactin levels. These results suggest that aripiprazole could act as a “net antagonist” in the nigrostriatal pathway, and that the development of EPS may be associated with lower prolactin levels in male subjects. Simultaneously, aripiprazole acts as a strong dose-dependent “net agonist” in the tuberoinfundibular pathway, and causes severe hypoprolactinemia that may be associated with adverse events in aripiprazole monotherapy.

Hypoprolactinemia and Extrapyramidal Symptoms in Male Schizophrenia or Psychotic Affective Disorder Patients Treated with Aripiprazole