The role of dopamine and glutamate modulation in Huntington disease.
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.


CONCLUSIONS
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.
Michael Trimble Neuropsychiatry Research Group, Department of Neuropsychiatry, BSMHFT and University of Birmingham, Birmingham, UK.
Sumeer K
SK
Mittal
Clare
C
Eddy
D001921:Brain / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000503:physiopathology*
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D004298:Dopamine