Department of Medicine & Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals Trust, Leeds, UK.
Lancet Gastroenterol Hepatol. 2018 Dec;3(12):837-844. doi: 10.1016/S2468-1253(18)30303-0. Epub 2018 Oct 22.
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. FUNDING: None.
背景：指南建议质子泵抑制剂（PPIs）和促动力剂治疗无反应的功能性消化不良患者使用神经调节剂；然而，随机对照试验缺乏支持其使用的数据。我们旨在评估三环抗抑郁药（TCA）丙咪嗪在治疗抵抗性功能性消化不良中的安全性和疗效。
方法：在这项单中心、双盲、随机对照试验中，我们纳入了符合罗马 II 功能性消化不良标准且年龄在 18-80 岁的连续患者。合格患者 Hp 阴性，上消化道内镜和腹部超声正常，且在接受埃索美拉唑 8 周和多潘立酮 4 周的开放性治疗后仍有症状。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列表以 1:1 的比例随机分配（头 2 周每晚 25mg，然后是 50mg）接受丙咪嗪或安慰剂治疗 12 周。主要终点是通过意向治疗人群中的患者报告评估，在 12 周时整体上对全球消化不良症状的满意缓解。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00164775，已完成。
结果：2005 年 9 月 11 日至 2010 年 8 月 20 日，107 例治疗抵抗性功能性消化不良患者被随机分配接受丙咪嗪（n=55）或安慰剂（n=52）。在丙咪嗪组中，55 例患者中有 35 例（63.6%，95%CI 50.4-75.1）在 12 周时对全球消化不良症状有缓解，而在安慰剂组中，52 例患者中有 19 例（36.5%，95%CI 24.8-50.1）（p=0.0051）。10 例（18%）丙咪嗪组患者因不良事件（3 例口干，2 例便秘，2 例嗜睡，1 例失眠、心悸和视力模糊各 1 例）停止研究，而安慰剂组有 4 例（8%）（1 例口干和便秘，1 例心悸，1 例胃食管反流恶化，1 例肢体感觉异常）（p=0.0051）。没有严重的不良事件。
结论：对于质子泵抑制剂和促动力剂治疗均无效的功能性消化不良患者，应考虑使用低剂量丙咪嗪，尽管应警告患者注意不良事件情况。
资助：无。
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