Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT.

IF 3.5 2区 医学 Q1 HEALTH CARE SCIENCES & SERVICES
Alexandra Wright-Hughes, Alexander C Ford, Sarah L Alderson, Pei Loo Ow, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Sonia Newman, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Hazel A Everitt, Amanda J Farrin
{"title":"Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT.","authors":"Alexandra Wright-Hughes, Alexander C Ford, Sarah L Alderson, Pei Loo Ow, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Sonia Newman, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Hazel A Everitt, Amanda J Farrin","doi":"10.3310/BFCR7986","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome, characterised by abdominal pain and a change in stool form or frequency, is most often managed in primary care. When first-line therapies are ineffective, National Institute for Health and Care Excellence guidelines suggest considering low-dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed by general practitioners.</p><p><strong>Objective: </strong>To evaluate the clinical and cost-effectiveness of low-dose titrated amitriptyline as a second-line treatment for irritable bowel syndrome in primary care.</p><p><strong>Design: </strong>A pragmatic, randomised, multicentre, two-arm, double-blind, placebo-controlled trial. A nested, qualitative study explored participant and general practitioner experiences of treatments and trial participation, and implications for wider use of amitriptyline for irritable bowel syndrome in primary care. Participants, clinicians, investigators and analysts were masked to allocation.</p><p><strong>Setting: </strong>Fifty-five general practices in three regions in England (Wessex, West of England, West Yorkshire).</p><p><strong>Participants: </strong>Patients aged ≥ 18 years meeting Rome IV criteria for irritable bowel syndrome with ongoing symptoms after trying first-line treatments and no contraindications to TCAs.</p><p><strong>Intervention: </strong>Amitriptyline 10 mg once-daily, self-titrated by participants to a maximum of 30 mg once-daily or matched placebo for 6 months. Participants randomised 1 : 1 with most having the option to continue blinded treatment for a further 6 months.</p><p><strong>Main outcome measures: </strong>The primary participant-reported outcome was the effect of amitriptyline on global irritable bowel syndrome symptoms at 6 months, measured using the irritable bowel syndrome Severity Scoring System, with a 35-point between-group difference defined as the minimum clinically important difference. The key secondary outcome was the proportion of participants reporting subjective global assessment of relief at 6 months, defined as somewhat, considerable, or complete relief of symptoms. Other secondary outcomes included: effect on global symptoms, via the irritable bowel syndrome Severity Scoring System, and subjective global assessment of relief of irritable bowel syndrome symptoms at 3 and 12 months; effect on somatic symptom-reporting at 6 months; anxiety an-d depression scores; ability to work and participate in other activities at 3, 6 and 12 months; acceptability, tolerability and adherence to trial medication.</p><p><strong>Results: </strong>Four hundred and sixty-three participants were randomised to amitriptyline (232) or placebo (231). An intention-to-treat analysis of the primary outcome showed a significant difference in favour of amitriptyline for irritable bowel syndrome Severity Scoring System score between arms at 6 months [-27.0, 95% confidence interval (CI) -46.9 to -7.10; <i>p</i> = 0.008]. For the key secondary outcome of subjective global assessment of relief of irritable bowel syndrome symptoms, amitriptyline was superior to placebo at 6 months (odds ratio 1.78, 95% CI 1.19 to 2.66; <i>p</i> = 0.005). Amitriptyline was superior to placebo across a range of other irritable bowel syndrome symptom measures but had no impact on somatoform symptom-reporting, anxiety, depression, or work and social adjustment scores. Adverse event trial withdrawals were more common with amitriptyline (12.9% vs. 8.7% for placebo) but most adverse events were mild. The qualitative study thematically analysed 77 semistructured interviews with 42 participants and 16 GPs. Most participants found the self-titration process acceptable and empowering.</p><p><strong>Conclusions: </strong>General practitioners should offer low-dose amitriptyline to patients with irritable bowel syndrome whose symptoms do not improve with first-line therapies. Guidance and resources should support GP-patient communication to distinguish amitriptyline for irritable bowel syndrome from use as an antidepressant and to support patients managing their own dose titration.</p><p><strong>Study registration: </strong>This trial is registered as ISRCTN48075063.</p><p><strong>Funding: </strong>This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/162/01) and is published in full in <i>Health Technology Assessment</i> Vol. 28, No. 66. See the NIHR Funding and Awards website for further award information.</p>","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491989/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Health technology assessment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3310/BFCR7986","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEALTH CARE SCIENCES & SERVICES","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Irritable bowel syndrome, characterised by abdominal pain and a change in stool form or frequency, is most often managed in primary care. When first-line therapies are ineffective, National Institute for Health and Care Excellence guidelines suggest considering low-dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed by general practitioners.

Objective: To evaluate the clinical and cost-effectiveness of low-dose titrated amitriptyline as a second-line treatment for irritable bowel syndrome in primary care.

Design: A pragmatic, randomised, multicentre, two-arm, double-blind, placebo-controlled trial. A nested, qualitative study explored participant and general practitioner experiences of treatments and trial participation, and implications for wider use of amitriptyline for irritable bowel syndrome in primary care. Participants, clinicians, investigators and analysts were masked to allocation.

Setting: Fifty-five general practices in three regions in England (Wessex, West of England, West Yorkshire).

Participants: Patients aged ≥ 18 years meeting Rome IV criteria for irritable bowel syndrome with ongoing symptoms after trying first-line treatments and no contraindications to TCAs.

Intervention: Amitriptyline 10 mg once-daily, self-titrated by participants to a maximum of 30 mg once-daily or matched placebo for 6 months. Participants randomised 1 : 1 with most having the option to continue blinded treatment for a further 6 months.

Main outcome measures: The primary participant-reported outcome was the effect of amitriptyline on global irritable bowel syndrome symptoms at 6 months, measured using the irritable bowel syndrome Severity Scoring System, with a 35-point between-group difference defined as the minimum clinically important difference. The key secondary outcome was the proportion of participants reporting subjective global assessment of relief at 6 months, defined as somewhat, considerable, or complete relief of symptoms. Other secondary outcomes included: effect on global symptoms, via the irritable bowel syndrome Severity Scoring System, and subjective global assessment of relief of irritable bowel syndrome symptoms at 3 and 12 months; effect on somatic symptom-reporting at 6 months; anxiety an-d depression scores; ability to work and participate in other activities at 3, 6 and 12 months; acceptability, tolerability and adherence to trial medication.

Results: Four hundred and sixty-three participants were randomised to amitriptyline (232) or placebo (231). An intention-to-treat analysis of the primary outcome showed a significant difference in favour of amitriptyline for irritable bowel syndrome Severity Scoring System score between arms at 6 months [-27.0, 95% confidence interval (CI) -46.9 to -7.10; p = 0.008]. For the key secondary outcome of subjective global assessment of relief of irritable bowel syndrome symptoms, amitriptyline was superior to placebo at 6 months (odds ratio 1.78, 95% CI 1.19 to 2.66; p = 0.005). Amitriptyline was superior to placebo across a range of other irritable bowel syndrome symptom measures but had no impact on somatoform symptom-reporting, anxiety, depression, or work and social adjustment scores. Adverse event trial withdrawals were more common with amitriptyline (12.9% vs. 8.7% for placebo) but most adverse events were mild. The qualitative study thematically analysed 77 semistructured interviews with 42 participants and 16 GPs. Most participants found the self-titration process acceptable and empowering.

Conclusions: General practitioners should offer low-dose amitriptyline to patients with irritable bowel syndrome whose symptoms do not improve with first-line therapies. Guidance and resources should support GP-patient communication to distinguish amitriptyline for irritable bowel syndrome from use as an antidepressant and to support patients managing their own dose titration.

Study registration: This trial is registered as ISRCTN48075063.

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/162/01) and is published in full in Health Technology Assessment Vol. 28, No. 66. See the NIHR Funding and Awards website for further award information.

低剂量滴定阿米替林作为成人肠易激综合征的二线治疗:ATLANTIS RCT。
背景:肠易激综合征以腹痛和大便形状或次数改变为特征,最常在初级保健中得到治疗。当一线治疗无效时,美国国家健康与护理优化研究所的指南建议考虑将低剂量三环类抗抑郁药作为二线治疗,但这些药物在基层医疗机构的疗效尚不清楚,而且全科医生也很少处方这些药物:目的:评估低剂量滴定阿米替林作为基层医疗机构肠易激综合征二线治疗的临床和成本效益:设计:一项务实、随机、多中心、双臂、双盲、安慰剂对照试验。一项嵌套定性研究探讨了参与者和全科医生在治疗和参与试验方面的经验,以及在基层医疗机构更广泛使用阿米替林治疗肠易激综合征的意义。参与者、临床医生、调查人员和分析人员均被蒙蔽:地点:英格兰三个地区(威塞克斯郡、英格兰西部、西约克郡)的 55 家全科诊所:年龄≥18岁、符合罗马IV标准的肠易激综合征患者,在尝试一线治疗后症状仍在持续,且无TCAs禁忌症:干预措施:阿米替林 10 毫克,每日一次,由参与者自行调整至最多 30 毫克,每日一次,或匹配安慰剂,为期 6 个月。参与者按 1 :主要结果测量:参与者报告的主要结果是阿米替林在6个月时对总体肠易激综合征症状的影响,采用肠易激综合征严重程度评分系统进行测量,35分的组间差异被定义为最小临床重要差异。关键的次要结果是在 6 个月时报告主观总体症状缓解的参与者比例,即症状有所缓解、相当缓解或完全缓解。其他次要结果包括:通过肠易激综合征严重程度评分系统对总体症状的影响,以及3个月和12个月时对肠易激综合征症状缓解情况的主观总体评估;6个月时对躯体症状报告的影响;焦虑和抑郁评分;3个月、6个月和12个月时工作和参与其他活动的能力;对试验药物的接受度、耐受性和依从性:463名参与者被随机分配到阿米替林(232例)或安慰剂(231例)中。对主要结果进行的意向治疗分析表明,在6个月的肠易激综合征严重程度评分系统得分方面,两组间的差异显著,阿米替林更胜一筹[-27.0,95%置信区间(CI)-46.9至-7.10;P = 0.008]。对于缓解肠易激综合征症状的主观总体评估这一关键次要结果,6个月时阿米替林优于安慰剂(几率比1.78,95% CI 1.19至2.66;P = 0.005)。在其他一系列肠易激综合征症状测量方面,阿米替林优于安慰剂,但对躯体形式症状报告、焦虑、抑郁或工作和社会适应评分没有影响。阿米替林的不良反应试验退出更常见(12.9% 对安慰剂的 8.7%),但大多数不良反应是轻微的。定性研究对与 42 名参与者和 16 名全科医生进行的 77 次半结构式访谈进行了专题分析。大多数参与者认为自我药量调节过程是可以接受的,而且能够增强能力:结论:全科医生应为使用一线疗法症状仍无改善的肠易激综合征患者提供小剂量阿米替林。指南和资源应支持全科医生与患者之间的沟通,将阿米替林治疗肠易激综合征与作为抗抑郁药使用区分开来,并支持患者自行管理剂量滴定:该试验的注册号为ISRCTN48075063:该奖项由美国国家健康与护理研究所(NIHR)健康技术评估项目资助(NIHR奖项编号:16/162/01),全文发表于《健康技术评估》第28卷第66期。如需了解更多奖项信息,请参阅 NIHR Funding and Awards 网站。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Health technology assessment
Health technology assessment 医学-卫生保健
CiteScore
6.90
自引率
0.00%
发文量
94
审稿时长
>12 weeks
期刊介绍: Health Technology Assessment (HTA) publishes research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信