不同剂量阿戈美拉汀对抑郁障碍患者肝功能的影响：一项真实世界研究

Effect of different doses of agomelatine on liver function in patients with depressive disorders： a real-world study

中文关键词:  阿戈美拉汀  抑郁障碍  肝功能  剂量效应  真实世界研究

英文关键词:Agomelatine  Depressive disorder  Liver function  Dose effect  Real-world study

中文摘要:

      背景 阿戈美拉汀是一种新型抗抑郁药，兼具改善情绪和调节睡眠的双重功效，已广泛应用于抑郁障碍的临床治疗。阿戈美拉汀与肝功能异常的关联逐渐引起关注，但关于真实临床场景中其对肝功能长期影响的研究有限。目的 探讨真实临床场景中，不同剂量阿戈美拉汀对抑郁障碍患者肝功能的影响，明确其安全性及疗效差异。方法 采用回顾性研究，纳入2019年1月—2024年12月在安徽医科大学附属巢湖医院精神科就诊、符合《国际疾病分类（第10版）》（ICD-10）抑郁障碍诊断标准且接受阿戈美拉汀治疗的200例患者为研究对象，基于真实世界数据进行纵向随访。根据阿戈美拉汀服用剂量，将患者分为低剂量组（25 mg/d）（n=121）和高剂量组（50 mg/d）（n=79），在基线进行评估，并在治疗第2、6、14、26周进行随访。采用全自动生化分析仪检测肝功能指标，包括谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）。采用汉密尔顿抑郁量表24项版（HAMD-24）和汉密尔顿焦虑量表（HAMA）评定患者的临床症状。结果 低剂量组和高剂量组ALT、AST、TBIL的时间效应、组间效应以及时间与组间的交互效应均无统计学意义（P均>0.05）。两组HAMD-24和HAMA评分的时间效应均有统计学意义（F_时间=430.573、395.737，P均<0.01），从治疗第2周末起，各随访时间点的评分均低于基线期（P均<0.01）。结论 低剂量和高剂量阿戈美拉汀对抑郁障碍患者的肝功能可能无明显影响，且不同剂量之间未观察到肝功能受损的差异。低剂量和高剂量的阿戈美拉汀可能均有助于减轻抑郁障碍患者的抑郁和焦虑症状。

英文摘要:

      Background Agomelatine， a novel antidepressant with dual efficacy in mood improvement and sleep regulation， has been widely utilized in clinical treatment of depressive disorders. The association between agomelatine and hepatic dysfunction has garnered increasing attention， yet there remains limited research on its long-term effect of liver function in real clinical scenarios.Objective To investigate the effect of different doses of agomelatine on liver function in patients with depressive disorders in real clinical scenarios， and to ascertain its safety profile and efficacy differences.Methods A retrospective study was conducted， enrolling 200 patients diagnosed with depressive disorders according to the International Classification of Diseases， tenth edition （ICD-10）， who received agomelatine treatment at the Department of Psychiatry of Chaohu Hospital Affiliated to Anhui Medical University from January 2019 to December 2024. Longitudinal follow-up was performed based on real-world data. Patients were divided into a low-dose group （25 mg/d） （n=121） and a high-dose group （50 mg/d） （n=79） based on their agomelatine dosage. Follow-up assessments were conducted at baseline， the 2^nd， 6^th， 14^th， and 26^th weeks after treatment initiation. Liver function indicators， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBIL）， were measured using a fully automated biochemical analyzer. Clinical symptoms were evaluated using the Hamilton Depression Scale-24 item （HAMD-24） and the Hamilton Anxiety Scale （HAMA）.Results No statistically significant time effect， intergroup effect， or time-by-group interaction effect was observed for ALT， AST， or TBIL in either the low-dose or high-dose group （P>0.05）. The time effects for both HAMD-24 and HAMA scores in the two groups were statistically significant （F_time=430.573， 395.737， P<0.01）. From the end of the 2^nd week of treatment onward， the scores at each follow-up time point were significantly lower than those at the baseline period （P<0.01）.Conclusion Both low-dose and high-dose agomelatine may have no significant effect on liver function in patients with depressive disorders， with no difference in liver function impairment was observed between dosage groups. Low-dose and high-dose agomelatine may be equally effective in alleviating depressive and anxiety symptoms in patients with depressive disorders. ［Funded by the Education Work Committee of the Anhui Provincial Committee for Outstanding Young Talents in Colleges and Universities （number， gxyqZD2022022）； the Key Project of Scientific Research Fund of Anhui Institute of Translational Medicine （number， 2023zhyx-B18）］