Authors: Bonelli, Raphael M.; Wenning, Gregor K.

Source: Current Pharmaceutical Design, Volume 12, Number 21, July 2006 , pp. 2701-2720(20)

Publisher: Bentham Science Publishers

Abstract:

Introduction: Despite the increasing body of published reports on pharmacological interventions in Huntington's disease (HD), an evidence based review (EBR) of treatment studies has not yet been published.

Method: Systematic literature searches were done using Medline (1965 - August 2005), the central database in the Cochrane Library (1969 - August 2005), and reference lists published in review articles and other clinical reports. Randomized controlled trials (RCTs) were classified as level-I-studies in this paper. Level-II evidence was assigned to nonrandomized, controlled clinical studies. Level-III-studies comprised open label trials excluding case reports. Measures of efficacy as well as safety and tolerability were considered for each compound.

Results: We identified 218 publications on pharmacological interventions in HD since 1965. Among them were 20 level-I, 55 level-II, 54 level-III trials, and 89 case reports. All these papers are listed and analyzed. Chorea was the primary end point in all level-I and level-II symptomatic intervention trials. There is some evidence for treating chorea with haloperidol or fluphenazine, and less evidence for olanzapine. These three drugs have been considered "possibly useful" for the treatment of chorea in this analysis. Other substances (e.g. amantadine, riluzole, and tetrabenazine) are considered "investigational" for chorea. There is very low evidence for the treatment of other problems: "possibly useful" drugs are L-dopa and pramipexole for rigidity; amitryptiline and mirtazapine for depression; risperidone for psychosis; and olanzapine, haloperidol, and buspirone for behavioral symptoms in HD. Three substances are considered "investigational" for possible neuroprotection: coenzyme Q10, minocycline, and unsaturated fatty acids.

Conclusion: There is poor evidence in management of HD today. The analysis of the twenty level-I studies fails to result in any treatment recommendation of clinical relevance. High-quality RCT are highly warranted to advance HD treatment in clinical practice.

Keywords: Huntington's disease; therapy; chorea; neuroleptics; neuroprotection

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161206777698693

Affiliations: 1: University Clinic of Psychiatry;Graz Medical University, Auenbruggerplatz 31, A-8036 Graz, Austria.

Publication date: 2006-07-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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