氟哌噻吨美利曲辛联合多潘立酮治疗伴有焦虑抑郁状态的功能性消化不良患者的疗效研究

Study on the efficacy of flupenthixol melitracen combined with domperidone in the treatment of patients with functional dyspepsia accompanied by anxiety and depression Shanghai Deanxit Clinical Trials

目的评价氟哌噻吨美利曲辛联合多潘立酮治疗伴有焦虑抑郁状态的功能性消化不良（FD）患者的疗效和不良反应。方法采用多中心、开放、随机、对照、前瞻性研究方法对8家研究中心伴有焦虑抑郁状态的FD患者进行临床试验。将患者分为对照组和试验组，对照组患者每日口服3次多潘立酮（10mg）治疗，试验组则在对照组治疗基础上每日早午饭后各予1片氟哌噻吨美利曲辛片（含氟哌噻吨0．5mg和美利曲辛10mg）治疗。入组时测量患者胃肠道症状评分、综合医院焦虑抑郁量表（HAD）、汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD），于治疗第1、2、4周随访，并记录不良反应。分别采用秩和检验、t检验和卡方检验分析数据。结果共209例患者纳入本研究，对照组105例，试验组104例。治疗前，两组患者的胃肠道症状、水负荷能力和综合医院抑郁情绪评分差异均无统计学意义（P均〉0．05），且试验组患者的综合医院焦虑情绪（t=2．405）、HAMA（t=3．982）和HAMD评分（t=3．374）均明显高于对照组（P均〈0．05）。治疗后1周两组患者症状均有所改善，且随着治疗时间的延长，疗效更加明显，但试验组的疗效始终优于对照组。试验组完全缓解率和显效率均显著高于对照组[分别为19．2％（20／104）比5．7％（6／105），37．5％（39／104）比11．4％（12／105），Z=4．935，P〈0．01]。治疗后4周试验组、HAD、HAMA和HAMD评分下降的幅度均明显大于对照组（HAD：Z=6．779，6．67，HAMA：Z=6．896，HAMD：Z=6．867，P均〈0．01）。此外，51．9％（54／104）伴抑郁状态的FD患者转归为正常，高于对照组的23．8％（25／105），差异有统计学意义（Z=20．460，P〈0．01）。治疗期间常见的不良反应为口干、便秘等，症状较轻微，无需特殊处理。结论氟哌噻吨美利曲辛联合多潘立酮治疗伴有焦虑抑郁状态的FD患者的疗效显著，无明显不良反应，值得临床推广应用。

Ohjeetive To evaluate the efficacy and adverse effects of flupenthixol meditracen combined with domperidone in the treatment of patients with functional dyspepsia（FD） accompanied by anxiety and depression. Methods The clinical trial was a multi centre, open, randomized, controlled, prospective study. The patients wiht FD accompanied by anxiety and depression from eight hospitals were divided into control group and experimentd group. The patients of control group were treated with domperidone 10 mg three times per day. On the basis of the treatment of control group, the patients of experimental group were given deanxit one tablet （flupentixol 0. 5 mg and melitracen 10 mg） after breakfast and lunch per day. The patients were evaluated by the gastrointestinal symptom rating scale（GSRS）, the hospital anxiety and depression scale （HAD）, the Hamilton anxiety scale （HAMA） and the Hamilton depression rating scale （HAMD） when enrolled and were followed up at the first, second and fourth week. The adverse effects were recorded. Using rank sum test, chisquare test and t-test to comparison of efficacy between the two groups, respectively. Results A total of 209 patients were enrolled during the trial, including 105 patients in control group and 104 patients in experimental group. Before the treatment, there were no statistical difference between the two groups in gastrointestinal symptoms, the water loading test and the hospital depression scale （all P~ 0.05）. However, the scores of hospitol anxiety scale, HAMA and HAMD in the experimental group were significantly higher than those of control group （t=2. 405, 3. 982,3. 374; all P^0.05）. After one week of treatment, the symptoms of both two groups improved. And the longer duration of the treatment, the more obvious of the efficacy. The efficacy of the experimental group was always better than that of the control group. Both of the complete remission rate and significant efficacy rate of the experimental group were higher than those of control group （19. 2%, 20/104 vs 5. 7~, 6/105; 37.5%, 39/104 vs 11. 4%, 12/105; Z=4. 935, P〈0. 01）. After four weeks of treatment, the decrease of the scores of HADS, HAMA and HAMD of experimental group was greater than those of control group （HAD：Z=6. 779, 6. 667, HAMA： Z= 6. 896; HAMD： Z 6. 867; all P〈0. 01）. Besides, 51.9 % （54/104） patients with FD accompanied by depression Became normal, the percentage was higher than that of control group （23.8~, 25/105） and the difference was statistically significant （2= 20. 460, P^0. 01）. During treatment, the common adverse effects were dry mouth and constipation, which were mild and needed no special treatment. Conclusion Flupenthicol melitracen combined with domperidone demonstrateds significant efficacy in the treatment of FD accompanied by anxiety and depression without obvious adverse effects and is worthy of clinical application.