Affiliations: The Michael Trimble Neuropsychiatry Research Group,
Department of Neuropsychiatry, BSMHFT and University of Birmingham, Birmingham,
UK
Note: [] Correspondence: Dr. Clare Eddy PhD, Department of
Neuropsychiatry, The Barberry National Centre for Mental Health, B15 2FG,
Birmingham, UK. Tel.: +44 121 3012317; Fax: +44 121 3012291; E-mail:
clare.eddy@bsmhft.nhs.uk
Abstract: Background: 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. Methods: 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. 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. Discussion: 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.
