Each week we will aim to bring out a concise email that provides 4-5 key pieces of information addressing a specific issue in clinical therapeutics.
This week: Huntington’s disease
Huntington’s disease (HD) is a rare, inherited neurodegenerative disorder of the central nervous system, caused by an expansion in the trinucleotide CAG in the huntingtin gene. Clinical features of the disease include involuntary choreiform movements, psychiatric disturbances, dementia, weight loss and circadian rhythm disturbances.
- Chorea is the involuntary movements of muscles, often initially occurring in fingers, toes and small facial muscles but later spreading to larger and more proximal muscle groups. Chorea is treated by dopamine receptor blocking or depleting agents such as antipsychotics and tetrabenazine.
- It should be noted that these treatments can potentially worsen other aspects of HD such as depressed mood and parkinsonism, and thus patients should be carefully monitored during dose titration. Tetrabenazine is the only drug that has been shown to significantly reduce chorea in HD in randomised controlled trials.
- Tetrabenazine causes depletion of dopamine and other monoamines in the central nervous system and is indicated for the treatment of chorea and other extrapyramidal disorders. Depression, which is common in HD, can be exacerbated by tetrabenazine.
- Antipsychotics are commonly used in the management of chorea as well as the psychiatric symptoms of HD. However, very few randomised controlled trials evaluating the efficacy and safety of antipsychotics in HD have been published. Olanzapine has been used in small open-label studies, with a 0-66% reduction in chorea. Supporting evidence for risperidone is limited, but case reports suggest potential benefit. Quetiapine, clozapine and aripiprazole have also been studied in small uncontrolled trials and have demonstrated some benefit. The choice of antipsychotic remains largely empirical and depends on the clinician’s experience.
- Atypical antipsychotics are usually the drugs of choice in treating the behavioural and psychiatric symptoms of HD. However, once again evidence for risperidone, olanzapine and quetiapine is limited to case reports and small open label studies. Quetiapine may be particularly useful as it seems to be less likely to cause deterioration in motor symptoms.
- Currently there is no cure for Hutnington’s disease, nor any treatments that are neuroprotective or disease-modifying. Management is based on treating symptoms in order to improve quality of life and to reduce the burden on families. Nonpharmacological strategies such as physiotherapy, occupational therapy and providing a calm, predictable environment may be beneficial.
Please consider these issues when preparing or interpreting RMMR reports or education sessions. Contributions of content or suggested topics are welcome and should be sent directly to email@example.com.