Wright-Hughes Alexandra, Ow Pei-Loo, Alderson Sarah L, Ridd Matthew J, Foy Robbie, Bishop Felicity L, Chaddock Matthew, Fernandez Catherine, Guthrie Elspeth A, Muir Delia P, Taylor Christopher A, Farrin Amanda J, Everitt Hazel A, Ford Alexander C
Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds, Leeds, UK.
Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK.
Gut. 2025 Apr 7;74(5):728-739. doi: 10.1136/gutjnl-2024-334490.
Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial.
To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA.
ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype.
There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs <50 on the IBS severity scoring system (IBS-SSS) (interaction p=0.048, mean difference in ≥50 years subgroup -46.5; 95% CI -74.2 to -18.8, p=0.0010), and subjective global assessment of relief (interaction p=0.068, OR in ≥50 years subgroup 2.59; 95% CI 1.47 to 4.55, p=0.0010), and those in the 70% most deprived areas of England compared with the 30% least deprived for a ≥30% improvement in abdominal pain (interaction p=0.021, OR in 70% most deprived subgroup 2.70; 95% CI 1.52 to 4.77, p=0.0007). Stronger treatment effects were seen in men, with higher Patient Health Questionnaire-12 scores, and with IBS with diarrhoea. Mean differences in individual IBS-SSS components favoured amitriptyline, and side effects were similar, across almost all IBS subtypes.
These exploratory analyses demonstrate there are unlikely to be deleterious effects of amitriptyline in any particular IBS subtype and could help identify patients in whom amitriptyline may be more effective.
ISRCTN48075063.
在低剂量三环类抗抑郁药（TCA）治疗肠易激综合征（IBS）的低剂量阿米替林滴定二线治疗肠易激综合征（ATLANTIS）试验中，低剂量阿米替林优于安慰剂。
对ATLANTIS试验进行事后分析，以确定TCA反应和耐受性的预测因素。
ATLANTIS试验将463例IBS成人患者随机分为阿米替林组（232例）和安慰剂组（231例）。我们研究了基线人口统计学和疾病相关患者特征对阿米替林反应的影响，以及阿米替林对各亚型个体症状和副作用的影响。
在IBS严重程度评分系统（IBS-SSS）中，≥50岁与<50岁患者在阿米替林疗效上存在数量差异（交互作用p=0.048，≥50岁亚组平均差异-46.5；95%CI -74.2至-18.8，p=0.0010），以及缓解的主观整体评估（交互作用p=0.068，≥50岁亚组OR 2.59；95%CI 1.47至4.55，p=0.0010），与英格兰最贫困地区30%相比，最贫困地区70%的患者腹痛改善≥30%（交互作用p=0.021，最贫困地区70%亚组OR 2.70；95%CI 1.52至4.77，p=0.0007）。在男性、患者健康问卷-12得分较高以及腹泻型IBS患者中观察到更强的治疗效果。几乎所有IBS亚型中，阿米替林在IBS-SSS各成分的平均差异方面更具优势，且副作用相似。
这些探索性分析表明，阿米替林在任何特定IBS亚型中不太可能产生有害影响，并有助于识别阿米替林可能更有效的患者。
ISRCTN48075063。
