The pathophysiology and pharmacological treatment of Huntington disease.
BACKGROUND
Huntington disease (HD) is a progressive neurodegenerative condition characterised by motor, cognitive and behavioural dysfunction, and has an autosomal dominant mode of inheritance. As there is currently no treatment to delay progression of the disease, pharmacological intervention is aimed at symptomatic relief.


METHODS
We set out to assess the current evidence on the pharmacological treatment of motor and non-motor symptoms in HD by carrying out a systematic literature review across five large scientific databases.


RESULTS
The search generated 23 original studies meeting our search criteria. Studies on the following drug classes were obtained: dopamine (DA) depleting agents, neuroleptics, anti-glutamatergic agents, acetylcholinesterase inhibitors, GABA agonists, cannabinoids, antidepressants and potential neuroprotective agents. Tetrabenazine (TBZ), a DA depleting agent, was the only pharmacotherapy shown to have a clinically meaningful, statistically significant effect on chorea. The majority of the reviewed studies focussed on the treatment of motor symptoms of HD.


CONCLUSIONS
Overall, the evidence base for the pharmacological management of HD is poor. There is a clear need for future high quality randomised controlled trials on the symptomatic treatment of HD, particularly on the pharmacotherapy of non-motor symptoms of HD.
Michael Trimble Neuropsychiatry Research Group, Department of Neuropsychiatry, BSMHFT and University of Birmingham, Birmingham, UK. CHP874@bham.ac.uk
Connie
C
Pidgeon
Hugh
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Rickards
D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001479:Basal Ganglia / Q000187:drug effects* / Q000503:physiopathology*; D002186:Cannabinoids / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D018755:GABA Agonists / Q000627:therapeutic use; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D013747:Tetrabenazine / Q000627:therapeutic use
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002186:Cannabinoids; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018696:Neuroprotective Agents; D013747:Tetrabenazine