Risk Factors for Amisulpride-Associated Hyperprolactinemia: Gender-Specific Plasma Concentration Cutoffs Derived from ROC Analysis.

PURPOSE: To investigate independent risk factors for amisulpride-induced hyperprolactinemia (HPRL), establish gender-stratified diagnostic cutoff values for HPRL, and determine amisulpride plasma concentration cutoff values for different genders, thereby providing a basis for personalized medication. PATIENTS AND METHODS: This retrospective study included 209 patients treated with amisulpride. Significant univariate variables were entered into multivariable linear regression to identify independent predictors. We used receiver operating characteristic (ROC) curve analysis to determine the overall prolactin cutoff of 28 ng/mL for identifying HPRL. Sex-stratified ROC analyses were further conducted to establish gender-specific optimal amisulpride plasma concentration thresholds. RESULTS: Daily amisulpride dose was positively correlated with plasma drug concentration (p < 0.001); multivariable analysis identified sex, plasma amisulpride concentration, and concomitant idebenone or lorazepam use as independent risk factors for amisulpride-induced prolactin elevation (p < 0.05). ROC analysis identified a screening cutoff value of 28 ng/mL for elevated prolactin levels in the overall population. Plasma amisulpride concentration cutoffs were higher in women (317.8 ng/mL) than in men (294.2 ng/mL), suggesting greater tolerance to higher plasma concentrations among women and confirming significant sex differences in susceptibility to amisulpride-induced prolactin elevation. CONCLUSION: Clinically, 28 ng/mL can be adopted as the screening cutoff value for elevated prolactin levels in patients treated with amisulpride, we advocate for sex-dependent plasma concentration management for personalized therapeutic drug monitoring to effectively prevent and control amisulpride-associated HPRL.