IMPACT OF ANTIPSYCHOTICS ON PROLACTIN LEVELS IN PEDIATRIC AND ADOLESCENT PATIENTS WITH PSYCHIATRIC DISORDERS IN REAL-WORLD PSYCHIATRIC CLINICAL PRACTICE
Authors: Wada *Shuhei , Iwamoto Kunihiro , Ikeda Masashi 
Published: February 2025

Abstract

Background
The prescription of antipsychotics in pediatrics and adolescents with psychiatric disorders has globally increased because of the increase in off-label use [1]. This raises concerns about the potential side effects of antipsychotics, notably hyperprolactinemia. Hyperprolactinemia can have various symptoms, including amenorrhea, galactorrhea, and sexual dysfunction, and can affect reproductive, immune, and endocrine functions [2]. Hypoprolactinemia is also associated with metabolic disturbances such as obesity and diabetes [3]. The distribution of abnormal prolactin levels in pediatric and adolescent patients under antipsychotic treatment is not well understood. Although many guidelines recommend regular prolactin monitoring with antipsychotic use, adherence is notably insufficient [4]. Previous reports regarding the effects of antipsychotics on prolactin levels have often been limited to unusual treatment settings such as those in randomized controlled trials, or to certain specific diagnoses, or cases involving specific antipsychotic drugs [2].

Aims & Objectives
Our aim was to evaluate serum prolactin levels in pediatric and adolescent patients with psychiatric disorders in the real-world psychiatric clinical setting and to identify potential correlations between antipsychotic treatment and abnormal prolactin levels.

Method
This study was a retrospective chart review of patients under 18 years of age with psychiatric disorders who were newly admitted to the Department of Psychiatry, Nagoya University Hospital, from September 2016 to October 2021. Serum prolactin levels were routinely measured upon admission. Patients without monitoring of serum prolactin levels and with comorbidities affecting prolactin levels, such as prolactinoma were excluded. Serum prolactin levels are known to vary with age and sex [5]. For children below 12 years of age, prolactin levels range from 3.9–25.4 ng/mL. For boys and girls over age 12 years, they are 4.1–18.4 ng/mL, and 3.4–24.1 ng/mL, respectively. In the present study, hyperprolactinemia and hypoprolactinemia were defined based on these criteria. We collected demographic information on patients, their prescribed antipsychotics, and respective dosages, and serum prolactin levels at admission. Serum prolactin levels were analyzed by using the Kruskal-Wallis test followed by post hoc analysis using the Bonferroni correction for Dunn’ s multiple comparisons among those using different antipsychotics and populations not on antipsychotics. This study was approved by the Bioethics Review Committee of Nagoya University Graduate School of Medicine (2005-0335).

Results
Three hundred and thirteen pediatric and adolescent patients (80.2% female, mean age: 14.9 years (standard deviation, 1.8) were included, and the most frequent diagnoses were feeding and eating disorders (35.4%) and neurodevelopmental disorders (23.3%). Of the 313 patients, 92 were prescribed antipsychotics. Hyperprolactinemia was observed in 26.1% in the antipsychotic group and hypoprolactinemia was observed in 6.5%. The antipsychotics risperidone, perospirone, and sulpiride significantly increased prolactin levels.

Discussion & Conclusion
Approximately one-third of the pediatric and adolescent patients hospitalized for any reason exhibited abnormal prolactin levels. It's important for clinicians to closely monitor prolactin levels and select antipsychotics with minimal impact on prolactin.

References
1.Piovani, D., Clavenna, A. & Bonati, M. 2019. Prescription prevalence of psychotropic drugs in children and adolescents: An analysis of international data. European Journal of Clinical Pharmacolology, 75, 1333-1346.
2.Kroigaard, S. M., Clemmensen, L., Tarp, S. & Pagsberg, A. K. 2022. A meta-analysis of antipsychotic- induced hypo- and hyperprolactinemia in children and adolescents. Journal of Child and Adolescent Psychopharmacology, 32, 374-389.
3.Macotela, Y., TRiebel, J. & Clapp, C. 2020. Time for a new perspective on prolactin in metabolism. Trends in Endocrinology and Metabolism, 31, 276-286.
4.Okumura, Y., Usami, M., Okada, T., Saito, T., Negoro, H., Tsujii, N., Fujita, J. & Iida, J. 2018. Glucose and prolactin monitoring in children and adolescents initiating antipsychotic therapy. Journal of Child and Adolescent Psychopharmacology, 28, 454-462.
5.Peuskens, J., Pani, L., Detraux, J. & De Hert, M. 2014. The effects of novel and newly approved antipsychotics on serum prolactin levels: A comprehensive review. CNS Drugs, 28, 421-53.