Li Qian ^1,2 Yun-Ai Su ¹ Xuemei Liao ¹ Maosheng Fang ³ Jianliang Gao ⁴ Jia Xu ⁵ Mingjun Duan ⁶ Haiying Yu ⁷ Yang Yang ⁸ Zhiyu Chen ⁹ Jintong Liu ¹⁰ Shaoxiao Yan ¹¹ Peifen Yao ¹² Shuying Li ¹³ Changhong Wang ¹⁴ Bin Wu ¹⁵ Congpei Zhang ⁵ Tianmei Si ^1*

• ¹ Peking University Sixth Hospital, Beijing, Beijing Municipality, China
• ² Peking University, Beijing, Beijing Municipality, China
• ³ Wuhan Mental Health Center, Wuhan, Hubei Province, China
• ⁴ The Fourth People’s Hospital of Hefei, Heifei, China
• ⁵ The First Harbin Psychiatric Hospital, Harbin, Jilin Province, China
• ⁶ Chengdu Fourth People's Hospital, Chengdu, Sichuan Province, China
• ⁷ The Chinese People's Liberation Army 904nd Hospital, ChangZhou, China
• ⁸ Beijing Anding Hospital, Capital Medical University, Beijing, Beijing Municipality, China
• ⁹ Hangzhou Seventh Peoples Hospital, Hangzhou, Zhejiang Province, China
• ¹⁰ Shandong Mental Health Center, Jinan, Shandong Province, China
• ¹¹ Beijing Huilongguan Hospital, Peking University, Beijing, Beijing Municipality, China
• ¹² Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, Shanghai Municipality, China
• ¹³ First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
• ¹⁴ Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China
• ¹⁵ Xian Mental Health Center, Xi'an, China

Objectives: To investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis. Methods: In this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups.The elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normal-prolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p<0.05). In total, 87.2% (68/78) patients experienced mild to moderate adverse events in the elevated-prolactin group, which was significantly more frequent compared with the normal-prolactin group 71.0% (365/514). Conclusions: In this real-world study, for patients with acute schizophrenia, aripiprazole was effective in lowering the proportion of patients with abnormal prolactin levels, while it had no significant effect on patients with normal baseline prolactin. After adjusting for factors such as sex, age, prior antipsychotic drugs use history and disease severity, effectiveness and safety of aripiprazole in patients with normal baseline prolactin was significantly better than that in patients with elevated baseline prolactin.