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      Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance

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          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.

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          Author and article information

          Contributors
          Journal
          PLoS Curr
          PLoS Curr
          plos
          PLoS Currents
          Public Library of Science (San Francisco, USA )
          2157-3999
          11 January 2016
          : 8
          : ecurrents.hd.8060298fac1801b01ccea6acc00f97cb
          Affiliations
          Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
          Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
          UCL Institute of Neurology, University College London, Queen Square, London, UK
          Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
          Psychiatry, University of Iowa, Iowa City, Iowa, USA
          Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
          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
          Neurology, Leiden University Medical Centre, Leiden, Netherlands
          Neurology, Ulm University, Ulm, Germany
          George-Huntington-Institute, Neurology, University of Münster, Münster, Germany
          CHDI Management/CHDI Foundation, Princeton, NJ, USA
          School of Psychological Sciences, Monash University, VIC, Australia
          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
          Neurodegenerative Disease, UCL Institute of Neurology, London, UK
          Article
          10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb
          4718719
          42f46aa7-dcdd-441d-9f8c-638674b2d49c
          © 2016 Keogh, Frost, Owen, Daniel, Langbehn, Leavitt, Durr, Roos, Landwehrmeyer, Reilmann, Borowsky, Stout, Craufurd, Tabrizi, et al

          This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

          History
          Funding
          TRACK-HD is supported by the CHDI Foundation, Inc., a not for profit organization dedicated to finding treatments for Huntington’s disease. The authors have declared that no competing interests exist.
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          Research Article

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