title: Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.
abstract: OBJECTIVE
  To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort.
  
  
  METHODS
  Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics.
  
  
  METHODS
  Primary and secondary care medical centers in the United States, Canada, Europe, and India.
  
  
  METHODS
  A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis.
  
  
  METHODS
  Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications.
  
  
  METHODS
  Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs).
  
  
  RESULTS
  There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant.
  
  
  CONCLUSIONS
  This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK. Electronic address: clive.ballard@kcl.ac.uk.
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.affiliation: Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL.
authors.forename: Stuart
authors.initials: S
authors.lastname: Isaacson
authors.affiliation: ACADIA Pharmaceuticals, San Diego, CA.
authors.forename: Roger
authors.initials: R
authors.lastname: Mills
authors.affiliation: ACADIA Pharmaceuticals, San Diego, CA.
authors.forename: Hilde
authors.initials: H
authors.lastname: Williams
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Corbett
authors.affiliation: ACADIA Pharmaceuticals, San Diego, CA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Coate
authors.affiliation: University of Kansas Medical Center, Kansas City, KS.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pahwa
authors.affiliation: Department of Clinical Pharmacology and Neurosciences, University UPS of Toulouse III, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
mesh_terms: D000058:Accidental Falls / Q000706:statistics & numerical data; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D004487:Edema / Q000453:epidemiology; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000453:epidemiology; D007239:Infections / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D010880:Piperidines / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology; D020521:Stroke / Q000453:epidemiology; D013923:Thromboembolism / Q000453:epidemiology; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D010880:Piperidines; D014508:Urea; C510793:pimavanserin
keywords: Parkinson disease; antipsychotics; mortality; psychosis; safety