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Antipsychotic-Related Prolactin Changes: A Systematic Review and Dose-Response Meta-analysis.

Xiao Lin^1,2, Spyridon Siafis^1,2, Jing Tian^1,2

¹Department of Psychiatry and Psychotherapy, School of Medicine and Health, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

|August 20, 2025

Summary

Antipsychotic drug doses significantly impact prolactin levels, with some medications posing higher risks. Clinicians should consider drug type, dosage, and patient sex when managing prolactin changes in schizophrenia treatment.

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Area of Science:

Pharmacology
Psychiatry
Clinical Therapeutics

Background:

Hyperprolactinemia is a frequent adverse effect of antipsychotic medications.
Understanding the dose-response relationship of antipsychotics with prolactin is crucial for patient management.

Purpose of the Study:

To investigate the association between antipsychotic doses and prolactin level alterations.
To analyze dose-response curves for various antipsychotics in adults with acute schizophrenia exacerbation.

Main Methods:

Systematic review and meta-analysis of randomized controlled trials (RCTs) of 21 antipsychotics.
Utilized restricted cubic spline methods for random-effects dose-response meta-analyses.
Primary outcome: mean prolactin change from baseline, measured in ng/mL.

Main Results:

Dose-response curves revealed that higher doses of aripiprazole were linked to lower prolactin levels.
Brexpiprazole, cariprazine, lumateperone, and quetiapine showed minimal prolactin increase risk across doses.
Most other antipsychotics demonstrated a dose-dependent increase in prolactin levels, with greater effects observed in females.

Conclusions:

The prolactin-elevating potential of antipsychotics is dose-dependent and sex-specific.
Findings aid clinicians in optimizing antipsychotic dosing and considering patient sex for treatment decisions.
Results are applicable to adults experiencing acute schizophrenia exacerbations.