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

Schizophr Res. 2017 Nov;189:134-141. doi: 10.1016/j.schres.2017.01.046. Epub 2017 Feb 20.


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 1year 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 1year 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 (χ2=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.

Keywords: Adherence; Antipsychotics; NCT: 02305823; Schizophrenia; Treatment.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Aripiprazole / therapeutic use
  • Brief Psychiatric Rating Scale
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Piperazines / therapeutic use
  • Prolactin / blood*
  • Prolactin / drug effects
  • Psychotic Disorders / blood*
  • Psychotic Disorders / drug therapy*
  • Quetiapine Fumarate / therapeutic use
  • Sex Characteristics
  • Thiazoles / therapeutic use
  • Time Factors
  • Young Adult


  • Antipsychotic Agents
  • Piperazines
  • Thiazoles
  • Quetiapine Fumarate
  • ziprasidone
  • Aripiprazole
  • Prolactin