Abstract
<i>Background:</i> Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes within the striatum are likely to lead to alterations in dopamine and glutamate activity in frontostriatal circuitry, resulting in characteristic motor, behavioural and cognitive symptoms.<i>Methods:</i> We conducted a systematic literature search in order to identify and review randomised, double-blinded, placebo-controlled trials of anti-dopaminergic and anti-glutamatergic therapy in HD.<i>Results:</i> Ten studies satisfied our selection criteria. These studies investigated a range of agents which act to antagonise dopamine (tetrabenazine, typical and atypical antipsychotics) or glutamate (amantadine, riluzole) transmission.<i>Discussion:</i> Although most agents showed efficacy in terms of amelioration of chorea, the available evidence did not allow us to identify a universally effective treatment. One difficulty associated with analysing the available evidence was a high prevalence of side effects, which prevented the full therapeutic potential of the medications from being adequately investigated. A further limitation is that many studies evaluated treatment effectiveness only in relation to patients' motor symptoms, even though behavioural and cognitive changes may negatively impact patients' quality of life. There is a clear need for further higher-level evidence addressing the effects of dopaminergic and glutamatergic agents on global functioning in HD.
Highlights
Huntington disease (HD) is a hereditary, hyperkinetic movement disorder, with a prevalence of approximately 4–8/100,000 in most countries
In this paper we review the efficacy of tetrabenazine, a range of neuroleptics and anti-glutamatergic therapy using high level evidence from clinical trials
Frank et al showed that the mean Unified Huntington’s Disease Rating Scale (UHDRS) chorea score increased by 5.3 units in the W group from days 1 to 3, compared with an increase of only 3.0 units in the ‘combined’ partial withdrawal group (PW) and NW groups. These results provide some evidence in support of TBZ being effective in controlling chorea, and no adverse effects were reported after abrupt treatment withdrawal
Summary
Huntington disease (HD) is a hereditary, hyperkinetic movement disorder, with a prevalence of approximately 4–8/100,000 in most countries. The autosomal dominant mutation is of the huntingtin gene, located on the short arm of the 4th chromosome This gene contains a repeated section of the trinucleotide CAG [1]. Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes within the striatum are likely to lead to alterations in dopamine and glutamate activity in frontostriatal circuitry, resulting in characteristic motor, behavioural and cognitive symptoms. Results: Ten studies satisfied our selection criteria These studies investigated a range of agents which act to antagonise dopamine (tetrabenazine, typical and atypical antipsychotics) or glutamate (amantadine, riluzole) transmission. A further limitation is that many studies evaluated treatment effectiveness only in relation to patients’ motor symptoms, even though behavioural and cognitive changes may negatively impact patients’ quality of life.
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