Effects of aripiprazole, quetiapine and ziprasidone on plasma prolactin levels in individuals with first episode nonaffective psychosis: Analysis of a randomized open-label 1 year study

Crespo-Facorro, Benedicto et al.[Rationale]: Hyperprolactinemia is considered a troubling adverse effect of antipsychotics. Direct comparisons among second generation antipsychotics are scant in clinical practice. We hypothesize prolactin-sparing second-generation antipsychotics may have differential effects on prolactin levels and that they may be influenced by sex. [Objectives]: To explore the differential effect of three widely used prolactin-sparing antipsychotics, aripiprazole, quetiapine and ziprasidone, on prolactin plasma levels in first episode non-affective psychosis during a 1 year of treatment. [Method]: From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. 141 patients who were randomly allocated to aripiprazole (N = 56), quetiapine (N = 36) or ziprasidone (N = 49) were analyzed. The main outcome was differences in prolactin plasma levels over 1 year follow-up among the three antipsychotics. Prolactin levels had a skewed distribution and therefore they were log-transformed before statistical analyses. [Results]: Male patients on aripiprazole had a lower risk of suffering an increase on prolactin plasma levels (N = 71; F = 12.645; p < 0.001). There was a gender effect with smaller changes in mean prolactin values only in males. Aripiprazole had a reduced risk of hyperprolactinemia (aripiprazole 19.6%) compared to quetiapine (44.4%) and ziprasidone (32.7%) (p = 0.038); and quite similar findings were found when investigating males (p = 0.040). No significant differences were found in females. The percentages of mild prolactin excess were: 14.3% on aripiprazole, 36.1% on quetiapine and 18.4% on ziprasidone (χ = 6.611 p = 0.037). [Conclusions]: Our findings provide additional evidence of differential effects of three sparing-prolactin antipsychotics on prolactin release and may help clinicians to decide among therapeutic options.The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos IIIPI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005- Orden sco/3246/2004, SENY Fundació Research Grant CI 2005-0308007 and Fundación Marqués de ValdecillaAPI07/011. Instituto de Salud Carlos IIIPIE14/00031 fondos FEDER.Peer Reviewe