THE ACUTE AND LONG-TERM EFFECT OF OLANZAPINE COMPARED WITH PLACEBO AND HALOPERIDOL ON SERUM PROLACTIN CONCENTRATIONS

Prolactin elevation is both a common and a persistent event with the c urrently marketed antipsychotics, excluding clozapine. Elevations have been associated with both acute (galactorrhea, amenorrhea) and chroni c (predisposition to osteoporosis) treatment-emergent adverse events. One of the defining criteria for an atypical antipsychotic is the rela tive lack of persistent prolactinemia. A double-blind, placebo- (N=68) and haloperidol- (Hal: 15+/-5 mg/day, N=69) controlled trial of three dose ranges of olanzapine (Olz-L: 5+/-2.5 mg/day, N=65; Olz-M: 10+/-2 .5 mg/day, N=64; Olz-H: 15+/-2.5 mg/day, N=69) in the treatment of sch izophrenia afforded the opportunity to assess the temporal course of t he influence of olanzapine and haloperidol on serum prolactin concentr ation. Consistent with its potent D-2 antagonism, haloperidol was asso ciated with a statistically significantly higher incidence of treatmen t-emergent prolactin elevation (72%) than seen with placebo (8%; p<0.0 01) at week 2 of therapy. Expectedly, this elevation was also persiste nt at weeks 4 and 6. In contrast, olanzapine-associated treatment-emer gent prolactin elevations were both lower in magnitude and transient. At week 2, 38% of the Olz-H, 24% of the Olz-M, and 13% of the Olz-L tr eatment groups exhibited a treatment-emergent prolactin elevation, wit h a mean increase of 0.35, 0.52, and 0.61 nmol/l, respectively; for ha loperidol the mean increase was 1.23 nmol/l. For only the Olz-M and th e Olz-H treatment groups did the week 2 incidence of treatment-emergen t prolactin elevations differ statistically significantly from placebo . Both the incidence of elevations and the mean increase in prolactin concentration were less than that seen with haloperidol. Furthermore, by treatment week 6, all three olanzapine groups exhibited incidences of treatment-emergent prolactin elevation that were comparable to plac ebo and were statistically significantly less than observed with halop eridol. Rapid adaptation was observed in the temporal course of prolac tin elevations associated with olanzapine based on both the categorica l analysis of treatment-emergent high values and the analyses of tempo ral change in mean concentrations. In contrast to haloperidol, the mag nitudes of the treatment-emergent elevations associated with olanzapin e were minimal. The rates of elevation were approximately one-half to one-third those observed with haloperidol and were significantly more transient. Olanzapine, even at the highest doses (15+/-2.5 mg/day) use d, was not associated with persistent elevations of prolactin, consist ent with an 'atypical' pharmacologic profile. (C) 1997 Elsevier Scienc e B.V.