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Clinical therapeutics
Q09 Valproic Acid for the treatment of aggressiveness in Huntington's disease: 1-year follow-up
  1. E Unti,
  2. S Mazzucchi,
  3. L Kiferle,
  4. U Bonuccelli,
  5. R Ceravolo
  1. Department of Neuroscience, University of Pisa, Pisa, Italy


Background Huntington's disease (HD) is characterised by involuntary movements, cognitive decline and psychiatric symptoms such as aggressiveness, and depression. In most cases involuntary movements and psychiatric symptoms are controlled by antipsychotic drugs, but sometimes side effects as parkinsonism or worsening of depression and apathy can reduce the therapeutic window of these drugs.

Aims To evaluate the beneficial effect of Valproic Acid on psychiatric symptoms such as agitation and aggressiveness as well as depression in HD.

Methods 10 symptomatic genetically confirmed HD patients (mean CAG repeat 40±2), mean disease duration (8±2 years) on antipsychotics, all with aggressiveness defined as disabling by the patients along with the care giver, were included in an open unblinded trial. Clinical evaluation including motor (UHDRS), psychiatric (NPI) and cognitive scales (MMSE) was performed at baseline and after 6 and 12 months of Valproic Acid (from 300 up to 1000 mg die).

Results In our cases we reported a reduction of 10 points of NPI score in each patient persisting 1 year after the introduction of Valproate without any side effect reported.

Conclusions The beneficial effect of Valproic Acid on aggressive patients is well documented since 19971 and, to our knowledge, there are only two case reports2 3 that support this effect in such psychiatric disturbance in HD. However no systematic study was done so far in this topic. Moreover, the successful use of Valproic acid in controlling aggressiveness allowed us not to increase the daily dose of neuroleptic, so preventing motor and psychiatric side effects.

References 1. Haas S, Vincent K, Holt J, et al. Divalproex: a possible treatment alternative for demented, elderly aggressive patients. Ann Clin Psychiatry 1997;9:145–7.

2. Grove VE Jr, Quintanilla J, DeVaney GT. Improvement of Huntington's disease with olanzapine and valproate. N Engl J Med 2000;343:973–4.

3. Rask G, Anderson C. Good effect of valproate against aggression in Huntington disease. Only two cases reported earlier. Lakartidningen 2010;107:3060–1.

  • Huntington's disease
  • aggressiveness

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