title: Antidopaminergic Medication is Associated with More Rapidly Progressive Huntington's Disease.
abstract: BACKGROUND
  Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder leading to progressive motor, cognitive and functional decline. Antidopaminergic medications (ADMs) are frequently used to treat chorea and behavioural disturbances in HD.
  
  
  OBJECTIVE
  We aimed to assess how the use of such medications was associated with the severity and progression of the motor aspects of the condition, given that there have been concerns that such drugs may actually promote neurological deterioration.
  
  
  METHODS
  Using multiple linear regression, supplemented by principal component analysis to explore the overall correlation patterns and help identify relevant covariates, we assessed severity and progression of motor symptoms and functional decline in 651 manifest patients from the REGISTRY cohort followed for two years. ADM treated versus non-treated subjects were compared with respect to motor impairment at baseline and progression rate by means of multiple regression, adjusting for CAG-repeat and age.
  
  
  RESULTS
  Patients treated with ADMs had significantly worse motor scores with greater functional disability at their first visit. They also showed a higher annual rate of progression of motor signs and disability over the next two years. In particular the rate of progression for oculomotor symptoms and bradykinesia was markedly increased whereas the rate of progression of chorea and dystonia was similar for ADM and drug naïve patients. These differences in clinical severity and progression could not be explained by differences in disease burden, duration of disease or other possible prognostic factors.
  
  
  CONCLUSIONS
  The results from this analysis suggest ADM treatment is associated with more advanced and rapidly progressing HD although whether these drugs are causative in driving this progression requires further, prospective studies.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Tedroff
authors.affiliation: Department of Pharmacology, Gothenburg University, Gothenburg, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Waters
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.affiliation: Department Neurology, LUMC Leiden, The Netherlands.
authors.forename: Raymund
authors.initials: R
authors.lastname: Roos
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D018450:Disease Progression; D015259:Dopamine Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D025341:Principal Component Analysis; D012042:Registries
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents
keywords: Huntington disease; antipsychotics; dopamine; observational study; tetrabenazine