Intervention Review

Therapeutic interventions for symptomatic treatment in Huntington's disease

  1. Tiago Mestre1,*,
  2. Joaquim Ferreira2,
  3. Miguel M Coelho2,
  4. Mário Rosa1,
  5. Cristina Sampaio2

Editorial Group: Cochrane Movement Disorders Group

Published Online: 8 JUL 2009

Assessed as up-to-date: 22 DEC 2007

DOI: 10.1002/14651858.CD006456.pub2

How to Cite

Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington's disease. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006456. DOI: 10.1002/14651858.CD006456.pub2.

Author Information

  1. 1

    Institute of Molecular Medicine, Neurological Clinical Research Unit, Lisboa, Portugal

  2. 2

    Faculdade de Medicina de Lisboa, Laboratório de Farmacologia Clínica e Terapêutica, Lisboa, Portugal

*Tiago Mestre, Neurological Clinical Research Unit, Institute of Molecular Medicine, Hospital de Santa Maria, Av. Prof. Egas Moniz, Lisboa, 1649-028, Portugal. tmestre@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 8 JUL 2009

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Huntington's disease (HD) is an orphan autosomal dominant neurodegenerative disorder caused by the amplification of a nucleic acids triplet repeat. It is characterised by core symptoms of chorea, progressive dementia and psychiatric manifestations such as depression, irritability, apathy and psychosis. In current clinical practice, drugs exist that seem to improve symptoms for HD patients. However, their effectiveness has not been fully measured.

Objectives

To evaluate the effectiveness of the available interventions for the symptomatic treatment of HD.

Search methods

The search strategy developed for the Movement Disorders Group was undertaken. Cochrane Controlled Trials Register, Medline, EMBASE and Clinical Trials Database of the United States National Institute of Health were thoroughly searched up until December 2007.

Selection criteria

All randomised, double-blinded, placebo-controlled clinical trials conducted on any symptomatic therapy used for HD with at least ten participants were included. Participants should have HD clinical features and a confirmatory genetic diagnosis or a compatible family history. All disease variants and ages of disease onset were included. Cross-over studies were included. All pharmacological and non-pharmacological interventions aimed at the control of signs and symptoms associated with HD were to be selected.

Data collection and analysis

Two reviewers independently assessed the identified trials for eligibility. In the selected trials, the assessment of their methodological quality was done according to the Cochrane Collaboration handbook, and eligible data were registered onto standardised forms. If possible, an intention-to-treat analysis was conducted. When data were not available in the original publication, the principal investigator of the trial was contacted. A meta-analysis was conducted when possible and otherwise the descriptive summary of the results was provided. The software Revman 5.0.15 was used for statistical analysis.

Main results

22 trials (1254 participants) were included. Nine trials had a cross-over design and 13 were conducted in parallel. Study duration ranged from 2 to 80 weeks. Various pharmacological interventions were studied, mostly, they were anti-dopaminergic drugs (n = 5), glutamate receptor antagonists (n = 5) and energy metabolites (n = 5). Only tetrabenazine showed a clear efficacy for the control of chorea. The remaining pharmacological interventions revealed no clear effectiveness.

Authors' conclusions

No intervention proved to have a consistent symptomatic control in HD. Tetrabenazine is the anti-choreic drug with the best quality data available. Other symptomatic areas should be explored by well-designed randomised placebo-controlled studies.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Interventions to control symptoms in Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. No curative therapy is currently available. We proposed to assess the effectiveness of interventions aimed at controlling the symptoms of HD and to analyse the methodological quality of the corresponding clinical trials. 22 trials were identified. The review of these trials comprising 1254 HD patients revealed that no intervention produced a robust conclusive symptomatic effect. Nevertheless, tetrabenazine was the drug for which better data exists supporting a beneficial effect in the treatment of chorea. There were no available data for the specific treatment of other clinical relevant problems associated with HD such as depression, irritability, apathy, cognitive impairment or psychosis.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

對亨廷頓氏症的症狀治療干預措施

亨廷頓氏症(HD)是一個染色體顯性遺傳神經退行性疾病,原因來自於擴增的核酸三核?酸重複。其特徵為有舞蹈症的主要症狀,持續惡化的痴呆,和精神上的表現如抑鬱,易怒,冷漠和精神病。在目前的臨床運用上,藥物似乎可以使HD的病人症狀緩解。然而,它們的有效性尚未被全盤的衡量。

目標

以評估對於HD現有的症狀治療的有效性。

搜尋策略

我們成立了動作障礙組的搜索策略。Cochrane Controlled Trials Register,Medline,EMBASE,和 Clinical Trials Database of the United States National Institute of Health皆被仔細得搜尋至2007年12月。

選擇標準

我們含括了所有對於HD症狀治療並最少有十位參加者的隨機,雙盲,安慰劑對照的臨床試驗。參加者必須有HD的臨床特點和可被證實的基因診斷或一個相符合的家族史。包括全部的疾病變異型和任何起始年齡。交叉研究也包括在內。選擇全部藥物和非藥物針對症狀控制的治療。

資料收集與分析

兩名評價員獨立評估以確認試驗的資格。在特定的試驗,評估其方法的品質是根據Cochrane協作手冊,並且將適合的資料註冊為標準形式。若可行的話,則進行意向性治療的分析。當資料在原稿中沒有提供,則連絡其試驗的主要研究者。我們賃可能做薈萃分析,不然就以說明性的摘要結果。對於統計分析我們用了software Rev Man 5.0.15。

主要結論

包括22的試驗(1254參加者)。其中九個試驗有交叉研究和另外13個同時進行。研究時間從2到80週。我們研究了不同藥物的嘗試,包括抗多巴胺藥物(n = 5),谷氨酸受體拮抗劑(n = 5),和能量代謝物(n = 5)。只有tetrabenazine對於舞蹈症有明顯的效果。其他藥物並沒有產生明顯的效果。

作者結論

對於HD的症狀控制是沒有一致有效的處理方式。Tetrabenazine是一種抗舞蹈症的藥並擁有最佳的數據。其他症狀應該要以設計良好的隨機安慰劑對照研究來做探索。

翻譯人

本摘要由新光醫院張安娜翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

亨廷頓氏症(HD)是一個染色體顯性遺傳神經退行性疾病。目前沒有可治癒的方法。我們提出以評估控制HD症狀的方法和其效果,並根據臨床試驗來評估其方法的品質。我們找出22個試驗。這些試驗的審查中,包括1254位HD的病人,結果發現沒有治療是可以對症狀有強大的效果。然而,tetrabenazine是一種藥擁有較好的數據支持對舞蹈症有其有利的效果。目前無對於HD相關臨床的問題有其他特定的治療,例如抑鬱,煩躁,冷漠,認知功能障礙或精神病。