Elevated prolactin and association with treatment resistance indicators in first-hospitalized schizophrenia spectrum...

Hyperprolactinemia frequently occurs during antipsychotic treatment but is also observed in antipsychotic-naïve schizophrenia patients. The relationship between prolactin (PRL) and treatment resistance remains underexplored in real-world populations.

To characterize age-/sex-stratified PRL distribution in first-hospitalized schizophrenia spectrum disorder (SSD) patients and examine associations with treatment resistance proxies (clozapine use/rehospitalization).

We analyzed 4,103 first-hospitalized SSD patients using real-world data. PRL levels were stratified by age/sex. Binary logistic regression evaluated PRL-clozapine/rehospitalization associations with confounder adjustment. ROC analysis assessed PRL's discriminative capacity for clozapine use.

Elevated PRL prevalence was highest in females aged 18-45 (71.5%). PRL negatively correlated with clozapine use in males (P < 0.001), with lower median levels in users vs. non-users (374.40 vs. 529.10 mIU/L, P < 0.001). This persisted in males aged 18-45 (434.90 vs. 558.60 mIU/L) and ≥ 55 years (308.60 vs. 583.30 mIU/L) (both P < 0.01). In males ≥ 55, each 1 mIU/L PRL increase reduced clozapine use probability by 0.2% (aOR = 0.998, 95%CI:0.997-1.000). ROC analysis showed moderate discriminative capacity (AUC = 0.72, sensitivity 78.6%, specificity 39.4%). No significant associations occurred in females or for rehospitalization.

The PRL demonstrates inverse, age-specific associations with clozapine use in male SSD patients, suggesting potential as a stratification biomarker for treatment resistance.