title: Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.
abstract: Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.
authors.affiliation: Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Keogh
authors.affiliation: Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Frost
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Owen
authors.affiliation: Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Daniel
authors.affiliation: Psychiatry, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Doug R
authors.initials: DR
authors.lastname: Langbehn
authors.affiliation: Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Blair
authors.initials: B
authors.lastname: Leavitt
authors.affiliation: Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Neurology, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.affiliation: Neurology, Ulm University, Ulm, Germany.
authors.forename: G Bernhard
authors.initials: GB
authors.lastname: Landwehrmeyer
authors.affiliation: George-Huntington-Institute, Neurology, University of Münster, Münster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Reilmann
authors.affiliation: CHDI Management/CHDI Foundation, Princeton, NJ, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Borowsky
authors.affiliation: School of Psychological Sciences, Monash University, VIC, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Stout
authors.affiliation: Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Craufurd
authors.affiliation: Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
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