title: Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients.
abstract: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes.
  
  
  
  We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes.
  
  
  
  Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term.
  
  
  
  Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021).
  
  
  
  Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia.
authors.affiliation: Robert Howard, MD, MRCPsych, Division of Psychiatry, University College London, and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London; Sergi G. Costafreda, MD, PhD, Division of Psychiatry, University College London, London, UK; Keith Karcher, MS, Danielle Coppola, MD, Janssen Research & Development, Jesse A. Berlin, ScD, Johnson & Johnson, David Hough, MD, Janssen Research & Development, Titusville, New Jersey, USA robert.howard@ucl.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Howard
authors.affiliation: Robert Howard, MD, MRCPsych, Division of Psychiatry, University College London, and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London; Sergi G. Costafreda, MD, PhD, Division of Psychiatry, University College London, London, UK; Keith Karcher, MS, Danielle Coppola, MD, Janssen Research & Development, Jesse A. Berlin, ScD, Johnson & Johnson, David Hough, MD, Janssen Research & Development, Titusville, New Jersey, USA.
authors.forename: Sergi G
authors.initials: SG
authors.lastname: Costafreda
authors.affiliation: Robert Howard, MD, MRCPsych, Division of Psychiatry, University College London, and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London; Sergi G. Costafreda, MD, PhD, Division of Psychiatry, University College London, London, UK; Keith Karcher, MS, Danielle Coppola, MD, Janssen Research & Development, Jesse A. Berlin, ScD, Johnson & Johnson, David Hough, MD, Janssen Research & Development, Titusville, New Jersey, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Karcher
authors.affiliation: Robert Howard, MD, MRCPsych, Division of Psychiatry, University College London, and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London; Sergi G. Costafreda, MD, PhD, Division of Psychiatry, University College London, London, UK; Keith Karcher, MS, Danielle Coppola, MD, Janssen Research & Development, Jesse A. Berlin, ScD, Johnson & Johnson, David Hough, MD, Janssen Research & Development, Titusville, New Jersey, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Coppola
authors.affiliation: Robert Howard, MD, MRCPsych, Division of Psychiatry, University College London, and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London; Sergi G. Costafreda, MD, PhD, Division of Psychiatry, University College London, London, UK; Keith Karcher, MS, Danielle Coppola, MD, Janssen Research & Development, Jesse A. Berlin, ScD, Johnson & Johnson, David Hough, MD, Janssen Research & Development, Titusville, New Jersey, USA.
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Berlin
authors.affiliation: Robert Howard, MD, MRCPsych, Division of Psychiatry, University College London, and Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London; Sergi G. Costafreda, MD, PhD, Division of Psychiatry, University College London, London, UK; Keith Karcher, MS, Danielle Coppola, MD, Janssen Research & Development, Jesse A. Berlin, ScD, Johnson & Johnson, David Hough, MD, Janssen Research & Development, Titusville, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hough
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000401:mortality*; D003704:Dementia / Q000188:drug therapy*; D006801:Humans; D018967:Risperidone / Q000009:adverse effects*
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone