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用于治疗儿童和青少年慢性非癌性疼痛的抗抑郁药。

Antidepressants for chronic non-cancer pain in children and adolescents.

作者信息

Cooper Tess E, Heathcote Lauren C, Clinch Jacqui, Gold Jeffrey I, Howard Richard, Lord Susan M, Schechter Neil, Wood Chantal, Wiffen Philip J

机构信息

Cochrane Pain, Palliative and Supportive Care Group, Pain Research Unit, Churchill Hospital, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.

出版信息

Cochrane Database Syst Rev. 2017 Aug 5;8(8):CD012535. doi: 10.1002/14651858.CD012535.pub2.


DOI:10.1002/14651858.CD012535.pub2
PMID:28779487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6424378/
Abstract

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Antidepressants have been used in adults for pain relief and pain management since the 1970s. The clinical impression from extended use over many years is that antidepressants are useful for some neuropathic pain symptoms, and that effects on pain relief are divorced and different from effects on depression; for example, the effects of tricyclic antidepressants on pain may occur at different, and often lower, doses than those on depression. Amitriptyline is one of the most commonly used drugs for treating neuropathic pain in the UK. OBJECTIVES: To assess the analgesic efficacy and adverse events of antidepressants used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any antidepressant with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed the evidence using GRADE and created three 'Summary of findings' tables. MAIN RESULTS: We included four studies with a total of 272 participants (6 to 18 years of age) who had either chronic neuropathic pain, complex regional pain syndrome type 1, irritable bowel syndrome, functional abdominal pain, or functional dyspepsia. All of the studies were small. One study investigated amitriptyline versus gabapentin (34 participants), two studies investigated amitriptyline versus placebo (123 participants), and one study investigated citalopram versus placebo (115 participants). Due to a lack of available data we were unable to complete any quantitative analysis.Risk of bias for the four included studies varied, due to issues with randomisation and allocation concealment (low to unclear risk); blinding of participants, personnel, and outcome assessors (low to unclear risk); reporting of results (low to unclear risk); and size of the study populations (high risk). We judged the remaining domains, attrition and other potential sources of bias, as low risk of bias. Primary outcomesNo studies reported our primary outcomes of participant-reported pain relief of 30% or greater or 50% or greater (very low-quality evidence).No studies reported on Patient Global Impression of Change (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) as very low. We downgraded the quality of the evidence by three levels to very low because there was no evidence to support or refute. Secondary outcomesAll studies measured adverse events, with very few reported (11 out of 272 participants). All but one adverse event occurred in the active treatment groups (amitriptyline, citalopram, and gabapentin). Adverse events in all studies, across active treatment and comparator groups, were considered to be a mild reaction, such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (very low-quality evidence).There were also very few withdrawals due to adverse events, again all but one from the active treatment groups (very low-quality evidence).No serious adverse events were reported across any of the studies (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for these secondary outcomes as very low. We downgraded the quality of the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful. AUTHORS' CONCLUSIONS: We identified only a small number of studies with small numbers of participants and insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of antidepressants to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.There is evidence from adult randomised controlled trials that some antidepressants, such as amitriptyline, can provide some pain relief in certain chronic non-cancer pain conditions.There is no evidence from randomised controlled trials to support or refute the use of antidepressants to treat chronic non-cancer pain in children or adolescents.

摘要

背景:疼痛是全球儿童和青少年的常见特征,对许多年轻人来说,这种疼痛是慢性的。世界卫生组织关于儿童持续性疼痛药物治疗的指南承认,儿童疼痛是世界上大多数地区高度重视的主要公共卫生问题。过去,疼痛大多被忽视且常常得不到治疗,但随着时间的推移,人们对儿童疼痛的看法发生了变化,现在疼痛缓解被视为很重要。我们设计了一组七项关于慢性非癌性疼痛和癌痛(涉及抗抑郁药、抗癫痫药、非甾体抗炎药、阿片类药物和对乙酰氨基酚)的综述,以回顾利用药物干预治疗儿童疼痛的证据。作为当今世界发病的主要原因,慢性病(及其相关疼痛)是一个主要的健康问题。慢性疼痛(即持续三个月或更长时间的疼痛)可在儿科人群中因多种病理生理分类(伤害性、神经性或特发性)而出现,包括遗传性疾病、神经损伤疼痛、慢性肌肉骨骼疼痛、慢性腹痛以及其他不明原因。自20世纪70年代以来,抗抑郁药已在成人中用于缓解疼痛和疼痛管理。多年广泛使用的临床印象是,抗抑郁药对某些神经性疼痛症状有用,而且对疼痛缓解的作用与对抑郁的作用不同且相互独立;例如,三环类抗抑郁药对疼痛的作用可能在与对抑郁不同且通常更低的剂量下出现。阿米替林是英国治疗神经性疼痛最常用的药物之一。 目的:评估用于治疗出生至17岁儿童和青少年慢性非癌性疼痛的抗抑郁药的镇痛效果和不良事件。 检索方法:我们通过Cochrane在线研究注册库检索了Cochrane对照试验中心注册库(CENTRAL),通过Ovid检索了MEDLINE,通过Ovid检索了Embase,检索时间从数据库创建至2016年9月6日。我们还检索了检索到的研究和综述的参考文献列表,并检索了在线临床试验注册库。 选择标准:随机对照试验,无论是否设盲,采用任何剂量和任何途径,治疗儿童和青少年慢性非癌性疼痛,比较任何抗抑郁药与安慰剂或活性对照药。 数据收集与分析:两位综述作者独立评估研究的纳入资格。我们计划使用二分数据,采用标准方法计算风险比和需治疗人数以获得一个额外事件。我们使用GRADE评估证据并创建了三个“结果总结”表。 主要结果:我们纳入了四项研究,共有272名参与者(6至18岁),他们患有慢性神经性疼痛、1型复杂性区域疼痛综合征、肠易激综合征、功能性腹痛或功能性消化不良。所有研究规模都较小。一项研究比较了阿米替林与加巴喷丁(34名参与者),两项研究比较了阿米替林与安慰剂(123名参与者),一项研究比较了西酞普兰与安慰剂(115名参与者)。由于缺乏可用数据,我们无法完成任何定量分析。纳入的四项研究的偏倚风险各不相同,原因包括随机化和分配隐藏问题(低至不清楚的风险);参与者、人员和结果评估者的盲法(低至不清楚的风险);结果报告(低至不清楚的风险);以及研究人群规模(高风险)。我们将其余领域,即失访和其他潜在偏倚来源,判定为低偏倚风险。主要结局没有研究报告我们的主要结局,即参与者报告疼痛缓解30%或更高或50%或更高(极低质量证据)。没有研究报告患者总体变化印象(极低质量证据)。我们将证据的总体质量(GRADE评级)评定为极低。我们将证据质量下调三个级别至极低,因为没有证据支持或反驳。次要结局所有研究都测量了不良事件,报告的很少(272名参与者中有11名)。除一项不良事件外,所有不良事件均发生在活性治疗组(阿米替林、西酞普兰和加巴喷丁)。所有研究中,活性治疗组和对照组的不良事件均被认为是轻度反应,如恶心、头晕、嗜睡、疲倦和腹部不适(极低质量证据)。因不良事件导致的退出也很少,同样除一项外均来自活性治疗组(极低质量证据)。所有研究中均未报告严重不良事件(极低质量证据)。我们其余次要结局的数据很少或没有(极低质量证据)。我们将这些次要结局的证据总体质量(GRADE评级)评定为极低。由于数据太少且事件数量太少以至于无意义,我们将证据质量下调三个级别至极低。 作者结论:我们仅识别出少数研究,参与者数量少且分析数据不足。由于我们无法进行荟萃分析,所以无法评论使用抗抑郁药治疗儿童和青少年慢性非癌性疼痛时的疗效或危害。同样,我们无法评论其余次要结局:照顾者总体变化印象;急救镇痛需求;睡眠时间和质量;治疗的可接受性;身体功能;以及生活质量。成人随机对照试验有证据表明,一些抗抑郁药,如阿米替林,在某些慢性非癌性疼痛情况下可提供一定程度的疼痛缓解。随机对照试验中没有证据支持或反驳使用抗抑郁药治疗儿童或青少年慢性非癌性疼痛。

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本文引用的文献

[1]
A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children.

Scand J Pain. 2016-10

[2]
Antiepileptic drugs for chronic non-cancer pain in children and adolescents.

Cochrane Database Syst Rev. 2017-8-5

[3]
Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

Cochrane Database Syst Rev. 2017-8-2

[4]
Paracetamol (acetaminophen) for chronic non-cancer pain in children and adolescents.

Cochrane Database Syst Rev. 2017-8-2

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Opioids for chronic non-cancer pain in children and adolescents.

Cochrane Database Syst Rev. 2017-7-26

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Non-steroidal anti-inflammatory drugs (NSAIDs) for cancer-related pain in children and adolescents.

Cochrane Database Syst Rev. 2017-7-24

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Opioids for cancer-related pain in children and adolescents.

Cochrane Database Syst Rev. 2017-7-19

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Pain. 2016-2

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Pediatr Rheumatol Online J. 2015-6-26

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