Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial
Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s2468-1253(18)30303-0
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发表时间：
2018-12-01
影响因子：
35.7
通讯作者：
Wu, Justin C. Y.
中科院分区：
文献类型：
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作者：
Cheong, Pui Kuan;Ford, Alexander C.;Wu, Justin C. Y.
背景指南建议对对质子泵抑制剂(PPI)和促动力作用无效的功能性消化不良患者使用神经调节剂；然而，缺乏支持其使用的随机对照试验的数据。我们旨在评价三环类抗抑郁药丙咪嗪治疗难治性功能性消化不良的安全性和有效性。方法在这项单中心、双盲、随机对照试验中，我们连续招募了年龄18-80岁的罗马II型功能性消化不良患者。符合条件的患者幽门螺杆菌阴性，上消化道内窥镜和腹部超声检查正常，在埃索美拉唑和多潘立酮开放治疗8周和4周后仍有症状。患者完成了评估消化不良症状、情绪和失眠的问卷，然后通过计算机生成的随机数字列表被随机分配(1：1)，接受丙咪嗪(前两周每晚一次，剂量为25毫克，此后为50毫克)或安慰剂治疗12周。主要终点是通过患者报告的有意治疗人群的评估，在12周时全球消化不良症状总体令人满意的缓解。这项试验在ClinicalTrials.gov注册，编号NCT00164775，并已完成。2005年9月11日至2010年8月20日，107名难治性功能性消化不良患者被随机分配接受丙咪嗪治疗(n=55)或安慰剂(n=52)。服用丙咪嗪的55名患者中有35名(63.6%，95%可信区间50.-4-75.1%)在12周后全球消化不良症状得到缓解，而服用安慰剂的52名患者中有19名(36.5%，95%可信区间24.8-50.1)(p=0.0051)。服用丙咪嗪的10名患者(18%)因不良事件(3名口干、2名便秘、2名昏昏欲睡，失眠、心悸和视力模糊各1名)而中止研究，而服用安慰剂的患者有4名(8%)(1名口干和便秘，各1名心悸、胃食道反流恶化和肢体感觉异常)。没有严重的不良事件。解释小剂量丙咪嗪应该被认为是对PPI和促动力都无效的功能性消化不良患者的一种可能的治疗方法，尽管患者应该注意不良事件的描述。版权所有(C)2018爱思唯尔有限公司。保留所有权利。
Background Guidelines recommend the use of neuromodulators in patients with functional dyspepsia not responding to proton pump inhibitors (PPIs) and prokinetics; however, there is a lack of data from randomised controlled trials supporting their use. We aimed to assess the safety and efficacy of imipramine, a tricyclic antidepressant (TCA), in treatment-refractory functional dyspepsia.Methods In this single-centre, double-blind, randomised controlled trial, we enrolled consecutive patients with Rome II functional dyspepsia aged 18-80 years. Eligible patients were Helicobacter pylori-negative, had a normal upper gastrointestinal endoscopy and abdominal ultrasound, and remained symptomatic after open-label treatment with 8 weeks of esomeprazole and 4 weeks of domperidone. Patients completed questionnaires assessing dyspepsia symptoms, mood, and insomnia, and were then randomly assigned (1:1) via a computer-generated list of random numbers to receive imipramine (at a dose of 25 mg once nightly for the first 2 weeks, and then 50 mg thereafter) or placebo for 12 weeks. The primary endpoint was overall satisfactory relief of global dyspepsia symptoms at 12 weeks, via patient-reported assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00164775, and is completed.Findings Between Sept 11, 2005, and Aug 20, 2010, 107 patients with treatment-refractory functional dyspepsia were randomly assigned to receive imipramine (n=55) or placebo (n=52). Relief of global dyspepsia symptoms at 12 weeks occurred in 35 (63.6%, 95% CI 50.-4-75.1) of 55 patients on imipramine compared with 19 (36.5%, 95% CI 24.8-50.1) of 52 on placebo (p=0.0051). Ten (18%) patients on imipramine discontinued the study due to adverse events (three dry mouth, two constipation, two drowsiness, and one each insomnia, palpitations, and blurred vision), compared with four (8%) on placebo (one dry mouth and constipation, and one each palpitations, worsening of gastro-oesophageal reflux, and limb paraesthesia). There were no serious adverse events.Interpretation Low-dose imipramine should be considered as a possible therapy for patients with functional dyspepsia refractory to both PPIs and prokinetics, although patients should be cautioned about the adverse event profile. Copyright (C) 2018 Elsevier Ltd. All rights reserved.