Possible individual and gender differences in the small increases in plasma prolactin levels seen during clozapine treatment.

In vitro, animal studies and acute short-term clinical studies suggest clozapine releases prolactin but the effect is much smaller than that of typical antipsychotics. Repeated early morning trough measures of plasma clozapine and prolactin levels on each subject were studied during the course of a double-blind dose-response clozapine study. After a 4-week 10 mg/day haloperidol trial and a one-week washout, treatment- refractory schizophrenics were successively randomized to 100, 300,or 600 mg/day of clozapine for a 16- week treatment. The statistical analyses included 35 subjects (19 females and 16 males). The within-subject correlation of prolactin levels was 0.32 with clozapine levels and 0.75 with haloperidol levels. An increment of 100 ng/ml in clozapine level yielded an average increment of 0.45 ng/ml of prolactin levels in females and of 0.15 ng/ml in males. An increment of 1 ng/ml in haloperidol level yielded an average increment of 2.6 ng/ml of prolactin levels in females and of 1.5 ng/ml in males. At least one fourth of patients demonstrated a significant and strong (r > 0.6) correlation between clozapine and prolactin levels. This study suggests that clozapine has effects on prolactin levels but effects are small and may be more evident in some individuals, particularly females.