修回日期: 2016-03-09
接受日期: 2016-03-23
在线出版日期: 2016-04-28
目的: 观察氟哌噻吨美利曲辛联合曲美布汀治疗伴有焦虑抑郁状态的腹痛明显的肠易激综合征(irritable bowel syndrome, IBS)患者的疗效.
方法: 本研究为多中心、随机、前瞻性研究, 将纳入的48例患者分为联合治疗组(24例)和对照组(24组). 两者均口服曲美布汀, 其中联合治疗组加用氟哌噻吨美利曲辛, 疗程为4 wk, 于治疗前、治疗1、4 wk同时进行胃肠道症状和情绪障碍评估. 统计学分析采用卡方检验.
结果: 治疗后1 wk, 联合治疗组与对照组的胃肠道症状改善有效率分别为16.7%和20.8%(P>0.05); 治疗后4 wk, 联合治疗组的胃肠道症状改善有效率为87.5%, 高于对照组的41.7%(χ2 = 9.507, P = 0.002). 治疗后1 wk, 联合治疗组与对照组的汉密尔顿抑郁量表(Hamilton Depression Scale, HAMD)评分有效率分别为14.3%和9.09%, 汉密尔顿焦虑量表(Hamilton Anxiety Scale, HAMA)评分有效率为25.0%和22.2%(P>0.05), 治疗后4 wk, 联合治疗组与对照组的HAMD评分有效率分别为61.9%和22.7%(χ2 = 6.776, P = 0.009), HAMA评分有效率为66.7%和33.3%(χ2 = 4.582, P = 0.032).
结论: 氟哌噻吨美利曲辛联合曲美布汀不仅可以有效改善腹痛明显的IBS的焦虑抑郁症状, 还可有效改善患者的消化系症状, 效果明显优于曲美布汀治疗.
核心提示: 本文利用氟哌噻吨美利曲辛联合曲美布汀治疗伴有焦虑抑郁的腹痛明显的肠易激综合征(irritable bowel syndrome, IBS)患者, 结果显示联合用药可有效改善腹痛明显的IBS的焦虑抑郁症状, 并可有效改善患者的消化道症状, 故应加强对精神心理因素的治疗.
引文著录: 韩静, 孙光斌, 张宝芹, 王柏清, 李甜甜. 氟哌噻吨美利曲辛联合曲美布汀治疗伴有焦虑抑郁的肠易激综合征患者的疗效评估. 世界华人消化杂志 2016; 24(12): 1916-1920
Revised: March 9, 2016
Accepted: March 23, 2016
Published online: April 28, 2016
AIM: To assess the therapeutic effects of flupentixol and melitracen tablets combined with trimebutine in patients with abdominal pain-predominant irritable bowel syndrome (IBS) accompanied with anxiety and depression.
METHODS: This multi-center, randomized, prospective study enrolled 48 patients with abdominal pain-predominant IBS who were divided into either a combination treatment group (24 patients) or a control group (24 patients). Trimebutine was administrated in both groups, while flupentixol and melitracen was added in the combination treatment group. The treatment lasted 4 wk. Gastrointestinal symptoms and mood disorders were evaluated before treatment, 1 wk and 4 wk after treatment.
RESULTS: At the end of one week after treatment, the rates of improvement of gastrointestinal symptoms in the combination treatment group and control group were 16.7% and 20.8%, and there was no statistically significant difference between them (P > 0.05). At the end of 4 wk after treatment, the rates of improvement of gastrointestinal symptoms in the combination treatment group was 87.5%, which was significantly higher than that of the control group (41.7%; χ2 = 9.507, P = 0.002). At the end of 1 week after treatment, there were no statistically significant differences in the rates of Hamilton Depression Scale score improvement (14.3% and 9.09%, P > 0.05) or the rates of Hamilton Anxiety Scale score improvement (25.2% vs 22.2%, P > 0.05) between the combination treatment group and control group. At the end of 4 weeks after treatment, the rate of Hamilton Depression Scale score improvement in the combination treatment group was significantly higher than that of the control group (61.9% vs 22.7%, χ2 = 6.776, P = 0.009), and the rate of Hamilton Anxiety Scale score improvement was also significantly higher in the combination treatment group (66.7% vs 33.3%, χ2 = 4.582, P = 0.032).
CONCLUSION: Flupentixol and melitracen combined with trimebutine could not only improve the anxiety and depression symptoms of patients with abdominal pain-predominant IBS, but also effectively improve gastrointestinal symptoms. The efficacy of the combination treatment is better than that of trimebutine monotherapy.
- Citation: Han J, Sun GB, Zhang BQ, Wang BQ, Li TT. Therapeutic effects of flupentixol and melitracen combined with trimebutine in patients with irritable bowel syndrome accompanied with anxiety and depression. Shijie Huaren Xiaohua Zazhi 2016; 24(12): 1916-1920
- URL: https://www.wjgnet.com/1009-3079/full/v24/i12/1916.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v24.i12.1916
肠易激综合征(irritable bowel syndrome, IBS)是一种常见的功能性肠病, 以腹痛或腹部不适为主要症状, 排便后可改善, 常伴有排便习惯改变, 缺乏可解释症状的形态学和生化学异常. 其病理生理机制包括消化系感觉和/或运动功能异常、黏膜分泌异常、肠道菌群失调等改变, 临床对于IBS主要采用止泻、解痉等对症治疗, 以缓解症状为目的. 本研究重点在于腹痛明显且伴有焦虑抑郁的IBS患者, 给予氟哌噻吨美利曲辛和曲美布汀联合治疗, 观察其疗效.
本研究为前瞻性研究, 采用随机对照的方法, 纳入2013-12/2014-12就诊于天津市第五中心医院的腹痛明显且伴有焦虑抑郁症的IBS患者48例. 纳入标准: (1)年龄为18-65岁; (2)IBS符合罗马Ⅲ诊断标准[1]; (3) HAMD评分为8-35分, 或HAMA评分为7-29分; (4)曾应用过抗抑郁药物的患者要度过清洗期(清洗期 = 药物半衰期×5). 所有纳入患者均签署知情同意书.
1.2.1 分组与治疗: 采取随机数表法将48例患者分成联合治疗组(24例)和对照组(24例). 两组患者均口服曲美布汀, 每次0.1 g, 每日3次. 其中联合治疗组均加用氟哌噻吨美利曲辛, 每日早、午餐后口服; 疗程为4 wk.
1.2.2 疗效评估: 于治疗前、治疗1 wk(8 d±1 d)、治疗4 wk(29 d±1 d)进行腹痛症状和情绪障碍评估. (1)胃肠道症状评估: 根据腹痛、大便形状等临床症状评分标准为, 无症状0分, 偶尔有症状但不影响正常生活, 计1分; 有时有症状影响正常生活但不显著, 计2分; 经常有症状明显影响生活工作计3分. 总是有症状几乎无法正常工作, 计4分; 胃肠道症状评分减分率为: (治疗前症状评分-治疗后症状评分)/治疗前症状评分×100%. 减分率>60%为有效, 30%-60%为进步, <30%为无效; (2)情绪障碍的评估: HAMD评分和HAMA评分减分率均为: (治疗前症状评分-治疗后症状评分)/治疗前症状评分×100%. 减分率>40%为有效, 30%-40%为进步, <30%为无效; HAMD评分<8分, HAMA<7分表明焦虑抑郁状态都不存在.
统计学处理 应用SPSS17.0统计软件进行统计学分析. 正态分布的计量资料以mean±s表示, 两组间比较采用t检验, 率的比较采用卡方检验. P<0.05为差异有统计学意义.
24例联合治疗组患者中, 年龄平均为45.6岁±13.1岁, 24例对照组年龄为47.8岁±11.4岁, 差异无统计学意义(P>0.05); 联合治疗组中男8例, 女16例; 对照组男9例, 女15例, 差异无统计学意义(P>0.05).
治疗1 wk后, 联合治疗组与对照组的胃肠道改善有效率差异无统计学意义(P>0.05), 治疗后4 wk, 联合治疗组的胃肠道症状改善有效率为87.5%, 高于对照组的41.7%(χ2 = 9.507, P = 0.002)(表1).
| 分组 | 治疗后1 wk胃肠道症状改善 | 治疗后4 wk胃肠道症状改善 | ||||
| 无效 | 进步 | 有效 | 无效 | 进步 | 有效 | |
| 联合治疗组 | 16(66.7) | 4(16.7) | 4(16.7) | 1(4.2) | 2(8.3) | 21(87.5) |
| 对照组 | 12(50.0) | 7(29.2) | 5(20.8) | 5(20.8) | 9(22.2) | 10(41.7) |
2.3.1 HAMD评估: 对照组和联合治疗组中符合HAMD评分标准的分别有22例和21例(表2), 治疗后1 wk, 联合治疗组与对照组的HAMD评分改善的有效率差异无统计学意义(P>0.05); 治疗4 wk后, 联合治疗组的评分改善的有效率高于对照组(χ2 = 6.776, P = 0.009).
| 分组 | n | 治疗后1 wk HAMD评分改善 | 治疗后4 wk HAMD评分改善 | ||||
| 无效 | 进步 | 有效 | 无效 | 进步 | 有效 | ||
| 联合治疗组 | 21 | 14(66.3) | 4(19.0) | 3(14.3) | 4(9.5) | 4(9.5) | 13(61.9) |
| 对照组 | 22 | 17(77.3) | 3(13.6) | 2(9.09) | 10(45.4) | 7(31.8) | 5(22.7) |
2.3.2 HAMA评估: 对照组和联合治疗组中符合HAMD评分标准的分别有18例和24例(表3), 治疗后1 wk联合治疗组与对照组的HAMA评分改善的有效率分别为25.0%和22.2%, 差异无统计学意义(P>0.05). 治疗后4 wk, 联合治疗组HAMA评分改善的有效率为66.7%, 高于对照组的33.3%, 差异有统计学意义(χ2 = 4.582, P = 0.032).
| 分组 | n | 治疗后1 wk HAMA评分改善 | 治疗后4 wk HAMA评分改善 | ||||
| 无效 | 进步 | 有效 | 无效 | 进步 | 有效 | ||
| 联合治疗组 | 24 | 12(50.0) | 6(25.0) | 6(25.0) | 3(12.5) | 5(20.8) | 16(66.7) |
| 对照组 | 18 | 12(66.7) | 2(11.1) | 4(22.2) | 8(44.4) | 4(22.2) | 6(33.3) |
IBS是世界范围内的多发病, 普通人群中患病率可高达5%-10%[2], 以中青年居多且多见于女性[3-5]. IBS 症状常影响患者的学习、生活和工作, 对患者的生存质量产生不同程度的负面影响[6-8], IBS患者较易寻求各种医疗帮助, 花费较多, 因此是值得重视的临床与社会问题.
目前证实IBS的腹痛症状与肠道平滑肌痉挛有关, 给予解痉药物可缓解腹痛症状, 比如曲美布汀, 许多研究表明解痉药物对腹痛、腹部不适有短期疗效. 曲美布汀是一种胃肠道运动双向调节剂. 他直接作用于消化系平滑肌上钾、钙离子通道和胃肠道神经丛阿片受体. 根据消化系处于不同的运动状态进行选择性调节离子通道和阿片受体, 使处于不正常运动状态的胃肠道恢复正常运动. 本研究中, 对照组采用曲美布汀治疗1和4 wk时进行胃肠道症状评估, 发现改善率分别为20.8%和41.7%; 这表明曲美布汀缓解胃肠道症状, 随着服药时间的延长, 有效率呈上升趋势. 联合治疗组在治疗1和4 wk时胃肠道症状改善率分别为16.7%和87.5%. 其中治疗4 wk时优于对照组, 提示氟哌噻吨美利曲辛联合曲美布汀可更有效的控制胃肠道症状.
54%-100%的IBS患者有精神症状, 其中以焦虑抑郁多见[9-14]. 2014年美国消化学会的IBS治疗指南中推荐使用调节精神类药物治疗IBS[15]. 氟哌噻吨美利曲辛是由氟哌噻吨和美利曲辛组成的合剂, 氟哌噻吨主要作用于突出前膜的多巴胺自身调节受体, 促进多巴胺的合成和释放, 使突出间隙中的多巴胺含量增加, 美利曲辛可抑制突出前膜对去甲肾上腺素和5-羟色胺的再摄取作用, 提高了突出间隙中单胺类递质的含量; 两种成分在治疗上相互协同, 缓解患者的焦虑抑郁情绪.
在有效控制患者情绪障碍的同时, 患者的胃肠道症状得到很大的改善, 联合治疗组明显优于单纯使用曲美布汀组. 这表明IBS患者中存在的焦虑抑郁情绪对于IBS的发生、发展有重要的作用.
总之, 对于合并焦虑抑郁的IBS患者, 单纯应用传统药物不能明显改善患者的症状, 应加强对精神心理因素的治疗.
肠易激综合征(irritable bowel syndrome, IBS)是世界范围内的多发病, 普通人群中患病率可高达5%-10%, 对患者的生存质量产生不同程度的负面影响, 是值得重视的临床与社会问题.
王小众, 教授, 福建医科大学附属协和医院消化内科
目前研究表明54%-100%的IBS患者有精神症状, 其中以焦虑抑郁多见. 因此观察氟哌噻吨美利曲辛联合曲美布汀治疗伴有焦虑抑郁状态的腹痛明显的IBS患者的疗效有重要意义.
本研究为前瞻性研究, 采用随机对照的方法, 表明氟哌噻吨美利曲辛联合曲美布汀治疗伴有焦虑抑郁状态的腹痛明显的IBS患者效果最佳.
本文研究表明对于合并焦虑抑郁的IBS患者, 单纯应用传统药物不能明显改善患者的症状, 应加强对精神心理因素的治疗, 临床医师可借鉴.
本研究对伴有焦虑抑郁的IBS患者分组, 采用氟哌塞吨美利曲率与曲美布汀进行治疗研究, 结果认为对伴焦虑抑郁的IBS患者, 选择抗焦虑抑郁药物有助于缓解症状, 提示在IBS中应重视心因性病因, 有一定临床意义.
编辑:郭鹏 电编:闫晋利
| 1. | Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480-1491. [PubMed] [DOI] |
| 2. | Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:712-721.e4. [PubMed] [DOI] |
| 3. | Zhu L, Huang D, Shi L, Liang L, Xu T, Chang M, Chen W, Wu D, Zhang F, Fang X. Intestinal symptoms and psychological factors jointly affect quality of life of patients with irritable bowel syndrome with diarrhea. Health Qual Life Outcomes. 2015;13:49. [PubMed] [DOI] |
| 4. | Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:991-1000. [PubMed] [DOI] |
| 5. | Adeyemo MA, Spiegel BM, Chang L. Meta-analysis: do irritable bowel syndrome symptoms vary between men and women? Aliment Pharmacol Ther. 2010;32:738-755. [PubMed] [DOI] |
| 6. | Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22-32. [PubMed] [DOI] |
| 7. | Tang YR, Yang WW, Wang YL, Lin L. Sex differences in the symptoms and psychological factors that influence quality of life in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2012;24:702-707. [PubMed] [DOI] |
| 8. | Park JM, Choi MG, Kim YS, Choi CH, Choi SC, Hong SJ, Jeong JJ, Lee DH, Lee JS, Lee KJ. Quality of life of patients with irritable bowel syndrome in Korea. Qual Life Res. 2009;18:435-446. [PubMed] [DOI] |
| 9. | Gwee KA, Bak YT, Ghoshal UC, Gonlachanvit S, Lee OY, Fock KM, Chua AS, Lu CL, Goh KL, Kositchaiwat C. Asian consensus on irritable bowel syndrome. J Gastroenterol Hepatol. 2010;25:1189-1205. [PubMed] [DOI] |
| 10. | Kabra N, Nadkarni A. Prevalence of depression and anxiety in irritable bowel syndrome: A clinic based study from India. Indian J Psychiatry. 2013;55:77-80. [PubMed] [DOI] |
| 11. | Stasi C, Bellini M, Costa F, Mumolo MG, Ricchiuti A, Grosso M, Duranti E, Metelli MR, Gambaccini D, Bianchi L. Neuroendocrine markers and psychological features in patients with irritable bowel syndrome. Int J Colorectal Dis. 2013;28:1203-1208. [PubMed] [DOI] |
| 12. | Surdea-Blaga T, Băban A, Dumitrascu DL. Psychosocial determinants of irritable bowel syndrome. World J Gastroenterol. 2012;18:616-626. [PubMed] [DOI] |
| 13. | Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM, Walters SJ, Underwood JE, Read NW. The role of psychological and biological factors in postinfective gut dysfunction. Gut. 1999;44:400-406. [PubMed] [DOI] |
| 14. | Bonavita V, De Simone R. Towards a definition of comorbidity in the light of clinical complexity. Neurol Sci. 2008;29 Suppl 1:S99-102. [PubMed] [DOI] |
| 15. | Weinberg DS, Smalley W, Heidelbaugh JJ, Sultan S. American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome. Gastroenterology. 2014;147:1146-1148. [PubMed] [DOI] |