1、23国际消化病杂志 2023 年 2 月第 43 卷第 1 期 Int J Dig Dis，February 25，2023，Vol.43，No.1 论著 阿戈美拉汀联合富马酸伏诺拉生治疗难治性胃食管 反流病的疗效分析侯永政 宋 岩 刘 响 王 瑄 苏 帅 陈 鑫 张毅宏 王邦茂 姜 葵【摘要】目的 通过观察难治性胃食管反流病（rGERD）患者治疗前后精神心理及睡眠情况的变化，探讨阿戈美拉汀联合富马酸伏诺拉生治疗 rGERD 的效果。方法 选择 2021 年 3 月至 2021 年 10 月于天津医科大学总医院就诊的 54 例 rGERD患者，分为常规组（26 例）和试验组（28 例）。常规组
2、给予富马酸伏诺拉生治疗，试验组在给予与常规组相同治疗的基础上，联合阿戈美拉汀治疗，疗程均为 8 周。采用胃食管反流病问卷（GERDQ）、抑郁症筛查量表（PHQ-9）、广泛性焦虑量表（GAD-7）及睡眠障碍评定量表（SDRS）对 2 组治疗前后的消化道症状、精神心理状态及睡眠情况进行比较，并采用治疗前后各项评分的差值比较 2 组的疗效。结果 2 组患者的性别构成、平均年龄、平均病程，以及治疗前 GERDQ、PHQ-9、GAD-7、SDRS 评分的差异均无统计学意义（P 均0.05）。治疗 8 周后，常规组治疗后 GERDQ 评分较治疗前下降（6.580.26）分比（10.000.32）分，差异有
3、统计学意义（P0.05）。试验组的治疗后 GERDQ、PHQ-9、GAD-7 及 SDRS 评分均较治疗前显著下降（6.640.19）分、（2.860.64）分、（1.640.54）分、（6.500.81）分比（10.930.41）分、（8.071.05）分、（5.570.93）分、（12.501.35）分，差异均有统计学意义（P 均0.05）。试验组治疗前后的 GERDQ、PHQ-9、GAD-7 及SDRS 评分差值均显著大于常规组 （4.270.33）分、（5.210.57）分、（3.930.53）分、（6.703.72）分比（3.420.31）分、（1.620.30）分、（0.880.3
4、7）分、（1.460.47）分，差异均有统计学意义（P 均0.05）。2 组患者治疗后均未发生不良反应。结论 rGERD 患者存在精神心理异常和睡眠障碍，阿戈美拉汀联合富马酸伏诺拉生治疗能显著改善 rGERD 患者的消化道症状，并能缓解睡眠障碍及抑郁、焦虑状态，联合用药的疗效优于单用富马酸伏诺拉生。【关键词】难治性胃食管反流病；抑郁；焦虑；睡眠障碍；阿戈美拉汀；疗效DOI:10.3969/j.issn.1673-534X.2022.06.006Efficacy of agomelatine in combination with vonprazan fumarat for refractory
5、 gastroesophageal reflux diseaseHOU Yongzheng,ZHANG Yihong.Department of Gastroenterology and Hepatology,Tianjin Beichen Hospital,Tianjin 300400,China;SONG Yan,LIU Xiang,WANG Xuan,SU Shuai,CHEN Xin,WANG Bangmao,JIANG Kui.Department of Gastroenterology and Hepatology,Tianjin Medical University Genera
6、l Hospital,Tianjin 300052,China【Abstract】Objective This paper intends to investigate the changes of mental and psychological status and sleep status of patients with refractory gastroesophageal reflux disease(rGERD)before and after treatment,and to explore the efficacy of agomelatine in combination
7、with vorolaxen fumarate in the treatment of rGERD.Methods Fifty-four patients with rGERD who were treated in Tianjin Medical 作者单位：300400 天津市北辰医院消化内科（侯永政、张毅宏）；300052 天津医科大学总医院消化内科（宋岩、刘响、王瑄、苏帅、陈鑫、王邦茂、姜葵）通信作者：王邦茂，Email:；姜葵，Email:24国际消化病杂志 2023 年 2 月第 43 卷第 1 期 Int J Dig Dis，February 25，2023，Vol.43，No.1
8、University General Hospital from March 2021 to October 2021 were assigned to the conventional group(26 cases)and the experimental group(28 cases).The conventional group was treated with vorolaxen fumarate,while the experimental group was treated in the same way as the conventional group but in combi
9、nation with agomelatine.Both groups were treated for 8 weeks.Gastroesophageal reflux disease questionnaire(GERDQ),depression screening scale(PHQ-9),generalized anxiety scale(GAD-7),and sleep disorder rating scale(SDRS)were used to compare the digestive tract symptoms,mental and psychological status,
10、and sleep status of the two groups before and after treatment,and the difference of each score before and after treatment was used to compare the efficacy of the two groups.Results There are no significant differences in gender composition,average age,average course of disease,and GERDQ,PHQ-9,GAD-7
11、and SDRS scores before treatment between the two groups(P0.05).After 8 weeks of treatment,the GERDQ score of the conventional group decreased(6.580.26)points versus(10.000.32)points),with a statistically significant difference(P0.05).The scores of GERDQ,PHQ-9,GAD-7,and SDRS in the experimental group
12、 after treatment are significantly decreased(6.640.19)points,(2.860.64)points,(1.640.54)points,(6.500.81)points versus(10.930.41)points,(8.071.05)points,(5.570.93)points,(12.501.35)points),with statistically significant differences(P0.05).The differences in GERDQ,PHQ-9,GAD-7,and SDRS scores before a
13、nd after treatment in the experimental group are significantly greater than that in the conventional group(4.270.33)points,(5.210.57)points,(3.930.53)points,(6.703.72)points versus(3.420.31)points,(1.620.30)points,(0.880.37)points,(1.460.47)points),with statistically significant differences(P0.05).T
14、here are no adverse reactions in both groups after treatment.Conclusions The patients with rGERD have psycho-psychological disorders and sleep disorders.The treatment of agomelatine in combination with vorolaxen fumarate can significantly improve the digestive tract symptoms of rGERD patients,and ca
15、n relieve sleep disorders,depression,and anxiety.The efficacy of combined treatment is better than that of vorolaxen fumarate alone.【Key words】Refractory gastroesophageal reflux disease;Depression;Anxiety;Sleep disorders;Agomelatine;Efficacy研究报道中国胃食管反流病（GERD）患病率 约 为 3.1%1，30%40%的 GERD 患 者 经 8 周质子泵抑制
16、剂（PPI）治疗后仍反复出现反流、烧心等症状2-4。系统回顾性分析显示 GERD 症状的严重程度及发作频率与患者的焦虑、抑郁严重程度及睡眠质量密切相关，且非糜烂性胃食管反流病（NERD）、难治性胃食管反流病（rGERD）患者的焦虑、抑郁严重程度明显高于其他类型的GERD 患者5-8。此外，GERD 与睡眠障碍相互影响，研究显示有夜间反流的糜烂性食管炎（EE）和NERD 患者的睡眠障碍发生率分别高达 80.0%和77.1%9；睡眠障碍或睡眠剥夺又可导致胃、食管对酸性内容物的痛觉过敏，从而加重烧心症状10。目前抗抑郁及改善睡眠的药物对 rGERD 的疗效尚不明确。本研究通过观察 rGERD 患者治疗前后精神心理及睡眠情况的变化，探讨了阿戈美拉汀（agomelatine）联合富马酸伏诺拉生（vonprazan fumarat）对 rGERD 患者的消化道症状及精神心理、睡眠障碍的治疗效果。1 研究对象与方法1.1 研究对象选择 2021 年 3 月至 2021 年 10 月于天津医科大学总医院消化内科门诊就诊的56例rGERD患者，按就诊顺序分为常规组和试验组，其中有 2 例失访，最终纳入