The Pathophysiology and Pharmacological Treatment of Huntington Disease

Introduction: 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. Discussion: 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.