Intervention Review

Gabapentin for chronic neuropathic pain and fibromyalgia in adults

  1. R Andrew Moore1,*,
  2. Philip J Wiffen1,
  3. Sheena Derry1,
  4. Thomas Toelle2,
  5. Andrew S C Rice3

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 27 APR 2014

Assessed as up-to-date: 17 MAR 2014

DOI: 10.1002/14651858.CD007938.pub3


How to Cite

Moore RA, Wiffen PJ, Derry S, Toelle T, Rice ASC. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD007938. DOI: 10.1002/14651858.CD007938.pub3.

Author Information

  1. 1

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK

  2. 2

    Technische Universität München, Department of Neurology, Munich, Germany

  3. 3

    Imperial College London, Pain Research, Department of Surgery and Cancer, Faculty of Medicine, London, UK

*R Andrew Moore, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. andrew.moore@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 27 APR 2014

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. 淺顯易懂的口語結論
  6. Резюме на простом языке

Background

This review is an update of a review published in 2011, itself a major update of previous reviews published in 2005 and 2000, investigating the effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage chronic neuropathic pain and fibromyalgia.

Objectives

To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain and fibromyalgia.

Search methods

We identified randomised trials of gabapentin for chronic neuropathic pain or fibromyalgia by searching the databases MEDLINE (1966 to March 2014), EMBASE (1980 to 2014 week 10), and CENTRAL in The Cochrane Library (Issue 3 of 12, 2014). We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources, and searched Clinicaltrials.gov. Searches were run originally in 2011 and the date of the most recent search was 17 March 2014.

Selection criteria

Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain or fibromyalgia with assessment of pain intensity, pain relief, or both, using validated scales. Participants were adults.

Data collection and analysis

Three review authors independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.

For efficacy, we calculated the number needed to treat to benefit (NNT), concentrating on at least 50% pain intensity reduction, and Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) definitions of at least moderate and substantial benefit. For harm we calculated number needed to treat for harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. We emphasised differences between conditions now defined as neuropathic pain, and other conditions like masticatory pain, complex regional pain
syndrome type 1 (CRPS-1), and fibromyalgia.

Main results

Seven new studies with 1919 participants were added. Another report (147 participants) provided results for a study already included, but which previously had no usable data. A further report (170 participants) used an experimental formulation of intrathecal gabapentin. Thirty-seven studies (5633 participants) studied oral gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 84% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. There was no first tier evidence.

Second tier evidence for the outcome of at least 50% pain intensity reduction, considered valuable by patients with chronic pain, showed that gabapentin was significantly better than placebo in postherpetic neuralgia (34% gabapentin versus 21% placebo; NNT 8.0, 95% CI 6.0 to 12) and painful diabetic neuropathy (38% versus 21%, NNT 5.9, 95% CI 4.6 to 8.3). There was insufficient information in other pain conditions to reach any reliable conclusion. There was no obvious difference between standard gabapentin formulations and recently-introduced extended-release or gastro-retentive formulations, or between different doses of gabapentin.

Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin could expect to have at least one adverse event (62%), withdraw because of an adverse event (11%), suffer dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (9%). Serious adverse events (3%) were no more common than with placebo.

There were insufficient data for direct comparisons with other active treatments, and only third tier evidence for other painful conditions.

Authors' conclusions

There was no top tier evidence that was unequivocally unbiased. Second tier evidence, with potentially important residual biases, showed that gabapentin at doses of 1200 mg or more was effective for some people with some painful neuropathic pain conditions. The outcome of at least 50% pain intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement of this degree of pain relief is associated with important beneficial effects on sleep interference, fatigue, and depression, as well as quality of life, function, and work. About 35% achieved this degree of pain relief with gabapentin, compared with 21% for placebo. Over half of those treated with gabapentin will not have worthwhile pain relief. Results might vary between different neuropathic pain conditions, and the amount of evidence for gabapentin in neuropathic pain conditions except postherpetic neuralgia and painful diabetic neuropathy, and in fibromyalgia, is very limited.

The levels of efficacy found for gabapentin are consistent with those found for other drug therapies in postherpetic neuralgia and painful diabetic neuropathy.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. 淺顯易懂的口語結論
  6. Резюме на простом языке

Gabapentin for chronic neuropathic pain and fibromyalgia in adults

Neuropathic pain is pain coming from damaged nerves. It differs from pain messages carried along healthy nerves from damaged tissue (a fall, cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines like paracetamol or ibuprofen are not effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain. Our understanding of fibromyalgia (a condition of persistent, widespread pain and tenderness, sleep problems, and fatigue) is poor, but fibromyalgia can respond to the same medicines as neuropathic pain.

Gabapentin was developed to treat epilepsy, but it is now used to treat various forms of chronic pain. On 17 March 2014 we performed searches to look for clinical trials where gabapentin was used to treat neuropathic pain or fibromyalgia. We found that 5633 participants had been involved in 37 studies of reasonable quality. They tested gabapentin against placebo for four weeks or more. Studies lasting only one or two weeks are unhelpful when pain can last for years.

Only two conditions had useful amounts of data - postherpetic neuralgia (chronic pain following shingles) and painful diabetic neuropathy (where nerves are damaged in diabetes). Gabapentin helped 3 or 4 people in 10 by reducing their pain by at least half, while with placebo only 2 in 10 had this result.

With gabapentin 6 people in 10 can expect to have some adverse events, including dizziness (2 in 10), somnolence (1 or 2 in 10), peripheral oedema (1 in 10), and gait disturbance (1 in 10). Serious adverse events (1 in 33) were no more common than with placebo. One person in 10 withdrew because of adverse events. Persons taking gabapentin can expect to have at least one adverse event (6 in 10), or stop taking gabapentin because of an adverse event (about 1 in 10).

Gabapentin is helpful for some people with chronic neuropathic pain or fibromyalgia. It is not possible to know beforehand who will benefit and who will not. Current knowledge suggests that a short trial is the best way of telling.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. 淺顯易懂的口語結論
  6. Резюме на простом языке

慢性神經病變痛和纖維肌痛成人患者的gabapentin治療

背景

本次文獻回顧為更新2011年發表的文獻回顧資料,該次文獻回顧本身即為2005年和2000年發表之文獻回顧的重大更新,探討gabapentin對慢性神經病變痛 (chronic neuropathic pain) (因神經受損而導致疼痛) 的療效。醫師會使用抗癲癇藥物 (antiepileptic drug),治療慢性神經病變痛和纖維肌痛 (fibromyalgia)。

目的

評估gabapentin對慢性神經病變痛和纖維肌痛的止痛效果及不良作用。

搜尋策略

我們搜尋MEDLINE (1966年至2014年3月)、EMBASE (1980年至2014年第10週) 和考科藍圖書館的CENTRAL(2014年第3次發行 [共12次]) 等資料庫,找出以gabapentin治療慢性神經病變痛或纖維肌痛的隨機試驗。我們自網路來源取得臨床試驗報告及摘要 (已發表和未發表試驗),並搜尋Clinicaltrials.gov。我們自2011年開始執行搜尋,最近一次搜尋日期為2014年3月17日。

選擇標準

隨機雙盲試驗,報告gabapentin對神經病變痛或纖維肌痛的止痛效果和不良作用,採用有效量表評估疼痛強度、疼痛緩解程度或兩者。試驗受試者為成人。

資料收集與分析

由3位文獻回顧作者,獨立萃取療效和不良事件資料、檢視試驗品質的相關問題,並評估偏差風險。本次文獻回顧採用三級證據 (three tiers of evidence) 進行分析。第一級證據源自符合現行最佳準則且偏差風險極低的資料 (結果相當於大幅減輕疼痛強度、不受退出試驗受試者影響的治療意向分析法 [intention-to-treat analysis];至少有200名受試者接受比較,試驗持續8至12週,採平行分組設計);第二級證據來自未能符合1項或多項上述準則,雖具一些偏差風險,但所進行的比較數量適當的資料;至於第三級證據則來自受試者人數少,因此極可能出現偏差,或使用臨床效用有限的結果,或兩者皆具的資料。

我們計算療效的益一需治數 (NNT),著重於至少減輕50%的疼痛強度,以及按臨床試驗的方法、測量和疼痛評估創議 (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials, IMMPAC) 定義,至少具有中等和大幅效益。我們也針對不良作用和退出試驗的情況,計算傷害的益一需治數 (NNH)。採固定效果模式 (fixed-effect model) 進行後設分析 (meta-analysis)。我們強調如今定義為神經病變痛的疾病,與其他例如咀嚼疼痛 (masticatory pain)、第一型複合性局部疼痛症候群 (complex regional pain syndrome type 1, CRPS-1) 及纖維肌痛等疾病之間的差異。

主要結果

本次文獻回顧新增7篇新試驗,包含1919名受試者。有1篇論文 (147名受試者) 雖為先前文獻回顧中已納入的試驗,但當時並無可使用的資料。另有1篇論文 (170名受試者) 使用gabapentin脊髓腔止痛 (intrathecal gabapentin) 的實驗配方。有37篇試驗 (5633名受試者) 探討口服gabapentin,採用每日劑量1200 mg以上,針對12種慢性疼痛疾病進行探究;有84%的試驗受試者患有帶狀皰疹後神經痛 (postherpetic neuralgia)、會疼痛的糖尿病性神經病變,或混合型神經病變痛。並無第一級證據。

關於疼痛程度至少降低50%的結果,若將慢性疼痛患者的評價納入考慮,則第二級證據顯示,gabapentin對帶狀皰疹後神經痛 (34%相對於21%;NNT為8.0,95% CI為6.0至12) 和會疼痛的糖尿病性神經病變 (38%相對於21%,NNT為5.9,95% CI為4.6至8.3) 的療效,顯著優於安慰劑。至於其他疼痛疾病則因資訊不足,無法得出可靠結論。標準gabapentin劑型和近期推出的緩釋劑型或胃滯留劑型,或各種劑量的gabapentin之間,並無明顯差異。

gabapentin的不良事件發生率顯著較高。預期使用gabapentin的患者至少會發生1項不良事件 (62%)、因不良事件而退出試驗 (11%)、感覺暈眩 (19%)、想睡 (14%)、周邊水腫 (7%) 和步態障礙 (gait disturbance) (9%)。嚴重不良事件的發生率 (3%),與安慰劑相似。

並無充分資料足以和其他有效治療進行直接比較,而其他疼痛疾病則僅有第三級證據。

作者結論

並未發現確實無偏差的頂級證據。可能具有重要殘餘偏差 (residual bias) 的第二級證據顯示,使用1200 mg以上劑量的gabapentin,可有效治療罹患某些疼痛性神經病變痛疾病的部分患者。疼痛強度至少降低50%的結果,被患者視為有效的治療結果,但必須能對睡眠不受干擾、疲倦和沮喪,以及生活品質、功能和工作產生重大的有利作用,才能達到此種程度的疼痛緩解效果。gabapentin治療組約有35%的患者,可達到此種疼痛緩解程度,相較之下安慰劑組患者則有21%的患者,疼痛程度至少降低50%。接受gabapentin治療的患者中,有一半以上的人疼痛並未得到滿意的緩解。不同的神經病變性疼痛疾病,可能會產生不同的結果,而且除了帶狀皰疹後神經痛、會疼痛的糖尿病性神經病變和纖維肌痛以外,關於gabapentin治療神經病變性疼痛疾病的證據,數量也非常有限。

gabapentin的止痛效果,與帶狀皰疹後神經痛和會疼痛的糖尿病性神經病變的其他藥物治療一致。

 

淺顯易懂的口語結論

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. 淺顯易懂的口語結論
  6. Резюме на простом языке

慢性神經病變痛和纖維肌痛成人患者的gabapentin治療

神經病變痛 (neuropathic pain) 是由於神經受損所導致的疼痛,有別於來自受損組織 (跌倒、割傷或膝關節炎) 並沿健康神經傳遞的疼痛訊息。神經病變痛的治療藥物,與治療受損組織所造成的疼痛不同。諸如paracetamol或 ibuprofen之類的藥物,對神經病變痛無效,但有時用來治療憂鬱症或癲癇的藥物,卻對部分神經病變痛的患者極為有效。我們對纖維肌痛 (fibromyalgia) (一種會出現持續性的廣泛性疼痛和壓痛、睡眠障礙和疲倦等症狀的疾病) 的瞭解不深,但可使用治療神經病變痛的藥物治療纖維肌痛。

藥廠研發gabapentin是為了治療癲癇,但如今則用來治療各種慢性疼痛。本次文獻回顧於2014年3月17日進行搜尋,找尋使用gabapentin治療神經病變痛和纖維肌痛的臨床試驗。我們找到37篇品質適當的試驗,共計包含5633名受試者。這些試驗的研究者讓受試者接受gabapentin或安慰劑治療4週以上,然後比較兩組患者的狀況。由於患者的疼痛可能持續數年,因此僅持續1或2週的試驗並無幫助。

只有2種疾病具有適當的資料量,即帶狀皰疹後神經痛 (postherpetic neuralgia) (罹患帶狀皰疹後的慢性疼痛),和會疼痛的糖尿病性神經病變 (神經受損的糖尿病患者)。gabapentin治療組中,每10人約有3至4人的疼痛程度可降低至少一半,但安慰劑組中則每10人中只有2人如此。

預期接受gabapentin治療時,每10人約有6人會發生一些不良事件,包括暈眩 (每10人有2人發生)、想睡 (每10人有1或2人發生)、周邊水腫 (每10人有1人發生) 和步態障礙 (每10人有1人發生)。gabapentin治療組的嚴重不良事件發生率 (33人中有1人發生),與安慰劑組相似。在10名退出試驗的患者中,有1人是因為不良事件而退出。預期使用gabapentin的患者至少會發生1項不良事件 (每10人中有6人發生),或因不良事件而停用gabapentin治療 (每10人中約有1人)。

gabapentin對某些慢性神經病變痛或纖維肌痛的患者的確有幫助,但無法事先得知gabapentin對哪些患者有效,對哪些患者無效。現有的知識顯示,短期試驗是解決這個問題的最佳方式。

譯註


翻譯者:臺北醫學大學實證醫學研究中心
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

 

Резюме на простом языке

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. 淺顯易懂的口語結論
  6. Резюме на простом языке

Габапентин при хронической невропатической боли и фибромиалгии у взрослых

Невропатическая боль – это боль, исходящая из поврежденных нервов. Она отличается от боли, передающейся здоровыми нервами из поврежденной ткани (падение, порез или артрит коленного сустава). Невропатическая боль лечится другими лекарствами, нежели боль от поврежденной ткани. Лекарственные средства, такие как парацетамол или ибупрофен не эффективны при невропатической боли, в то время как лекарства, применяемые для лечения депрессии или эпилепсии, могут быть очень эффективными у некоторых пациентов с невропатической болью. Наше понимание фибромиалгии (состояние постоянной, широко распространенной боли и болезненности [при дотрагивании или давлении], c проблемами со сном и утомляемостью) оставляет желать лучшего, но фибромиалгия может отзываться на те же лекарства, что и невропатическая боль.

Габапентин был разработан для лечения эпилепсии, но в настоящее время используется и для лечения различных форм хронической боли. 17 марта 2014 мы провели поиск клинических исследований, в которых габапентин применялся для лечения невропатической боли или фибромиалгии. Мы обнаружили, что 5633 участника были включены в 37 исследований приемлемого качества. Они [исследования] проверяли габапентин против плацебо в течение четырех недель и более. Учитывая, что боль [хроническая] может длиться годами, исследования продолжительностью только одну или две недели бесполезны.

Только при двух состояниях (нарушениях здоровья) были пригодные объемы данных - постгерпетическая невралгия (хроническая боль при опоясывающем лишае) и болезненная диабетическая невропатия (поражение нервов при диабете). Габапентин помогал 3 или 4 людям из 10, уменьшая их боль, по крайней мере, наполовину, в то время как в группе плацебо только у 2 из 10 был такой же результат.

При приеме габапентина 6 человек из 10 могут ожидать некоторые неблагоприятные события, в том числе головокружение (2 из 10), сонливость (1 или 2 из 10), периферические отеки (1 из 10), и нарушения походки (1 из 10). Серьезных неблагоприятных событий (1 из 33) было не больше, чем при приеме плацебо. Один человек в 10 вышел из исследований из-за неблагоприятных событий. Лица, принимающие габапентин, могут ожидать, по крайней мере, одно неблагоприятное событие (6 из 10), или прекратят прием габапентина из-за неблагоприятного события (примерно 1 из 10).

Габапентин полезен некоторым людям с хронической невропатической болью или фибромиалгией. Нельзя знать заранее, кому поможет, а кому нет. Современные знания позволяют предполагать, что краткосрочные исследования – лучший способ убедиться в этом.

Заметки по переводу

Перевод: Абакумова Татьяна Рудольфовна. Редактирование: Александрова Эльвира Григорьевна, Зиганшина Лилия Евгеньевна. Координация проекта по переводу на русский язык: Казанский федеральный университет. По вопросам, связанным с этим переводом, пожалуйста, свяжитесь с нами по адресу: lezign@gmail.com