PMID- 26239690 OWN - NLM STAT- MEDLINE DCOM- 20160719 LR - 20220321 IS - 1538-9375 (Electronic) IS - 1525-8610 (Linking) VI - 16 IP - 10 DP - 2015 Oct 1 TI - Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis. PG - 898.e1-7 LID - S1525-8610(15)00442-9 [pii] LID - 10.1016/j.jamda.2015.06.021 [doi] AB - OBJECTIVES: 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. DESIGN: Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. SETTING: Primary and secondary care medical centers in the United States, Canada, Europe, and India. PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. CI - Copyright (c) 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved. FAU - Ballard, Clive AU - Ballard C AD - Wolfson Centre for Age-Related Diseases, King's College London, London, UK. Electronic address: clive.ballard@kcl.ac.uk. FAU - Isaacson, Stuart AU - Isaacson S AD - Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL. FAU - Mills, Roger AU - Mills R AD - ACADIA Pharmaceuticals, San Diego, CA. FAU - Williams, Hilde AU - Williams H AD - ACADIA Pharmaceuticals, San Diego, CA. FAU - Corbett, Anne AU - Corbett A AD - Wolfson Centre for Age-Related Diseases, King's College London, London, UK. FAU - Coate, Bruce AU - Coate B AD - ACADIA Pharmaceuticals, San Diego, CA. FAU - Pahwa, Rajesh AU - Pahwa R AD - University of Kansas Medical Center, Kansas City, KS. FAU - Rascol, Olivier AU - Rascol O AD - Department of Clinical Pharmacology and Neurosciences, University UPS of Toulouse III, Toulouse, France. FAU - Burn, David J AU - Burn DJ AD - Institute of Neuroscience, Newcastle University, Newcastle, UK. LA - eng SI - ClinicalTrials.gov/NCT00550238 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150801 PL - United States TA - J Am Med Dir Assoc JT - Journal of the American Medical Directors Association JID - 100893243 RN - 0 (Antiparkinson Agents) RN - 0 (Antipsychotic Agents) RN - 0 (Piperidines) RN - 8W8T17847W (Urea) RN - JZ963P0DIK (pimavanserin) SB - IM MH - Accidental Falls/statistics & numerical data MH - Adult MH - Aged MH - Aged, 80 and over MH - Antiparkinson Agents/therapeutic use MH - Antipsychotic Agents/administration & dosage/*adverse effects MH - Drug Therapy, Combination MH - Edema/epidemiology MH - Female MH - Humans MH - Hypotension, Orthostatic/epidemiology MH - Infections/epidemiology MH - Male MH - Middle Aged MH - Parkinson Disease/complications/drug therapy/*mortality MH - Piperidines/therapeutic use MH - Psychotic Disorders/*drug therapy/etiology MH - Stroke/epidemiology MH - Thromboembolism/epidemiology MH - Urea/analogs & derivatives/therapeutic use OTO - NOTNLM OT - Parkinson disease OT - antipsychotics OT - mortality OT - psychosis OT - safety EDAT- 2015/08/05 06:00 MHDA- 2016/07/20 06:00 CRDT- 2015/08/05 06:00 PHST- 2015/06/23 00:00 [received] PHST- 2015/06/24 00:00 [accepted] PHST- 2015/08/05 06:00 [entrez] PHST- 2015/08/05 06:00 [pubmed] PHST- 2016/07/20 06:00 [medline] AID - S1525-8610(15)00442-9 [pii] AID - 10.1016/j.jamda.2015.06.021 [doi] PST - ppublish SO - J Am Med Dir Assoc. 2015 Oct 1;16(10):898.e1-7. doi: 10.1016/j.jamda.2015.06.021. Epub 2015 Aug 1.