A disproportionality analysis of antipsychotic-induced hyperprolactinemia based on FDA adverse event reporting system

This study aims to compare the risks of different antipsychotics in causing hyperprolactinemia, taking into account the age, gender, and onset time.

We searched the FDA Adverse Event Reporting System (FAERS) from January 1, 2004, to March 31, 2022, for reports of hyperprolactinemia treated with antipsychotics. We evaluated the association between antipsychotics and the risk of hyperprolactinemia using reporting odds ratio (ROR) based on a disproportionality analysis. Moreover, information regarding age, gender, countries, and onset time was collected.

We found 4,430 reports of antipsychotic-induced hyperprolactinemia involving 13 different antipsychotics. From highest to lowest ROR value, the top five antipsychotics were as follows: risperidone (ROR = 631.0611; 95% CI: 592.7329, 671.8677) > amisulpride (ROR = 59.4425; 95% CI: 19.0668, 185.317) > paliperidone (ROR = 31.9885, 95% CI: 27.912, 36.6604) > fluphenazine (ROR = 15.6026; 95% CI: 5.0236, 48.4595) > haloperidol (ROR = 14.3861; 95% CI: 11.173, 18.5231). Except for three drugs (risperidone, haloperidol, and amisulpride), women outnumbered men in cases of antipsychotic-induced hyperprolactinemia. The age range was 13 - 64 years old, with the most being 19 - 44 years old, followed by 45 - 64 years old, and there were fewer elderly patients. From longest to shortest, the median onset time of these antipsychotics was as follows: cariprazine (305 days) > risperidone (304 days) > quetiapine (276 days) > haloperidol (183 days) > ziprasidone (54 days) > lurasidone (44.5 days) > olanzapine (41 days) > asenapine (15.5 days) > paliperidone (15 days) > aripiprazole (12 days) > clozapine (6 days).

Risperidone had the greatest risk of increasing prolactin, whereas clozapine had the lowest. Antipsychotic-induced hyperprolactinemia was more common in women and middle-aged patients. Clozapine had the shortest onset time in raising prolactin, whereas cariprazine had the longest.