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Original Investigation |

Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease

Daniel Weintraub, MD1,2,3,4; Claire Chiang, PhD5; Hyungjin Myra Kim, ScD5,6; Jayne Wilkinson, MD, MSCE1,3,4; Connie Marras, MD, PhD7; Barbara Stanislawski, MPH, MSW5; Eugenia Mamikonyan, MS3,4; Helen C. Kales, MD5,8,9
[+] Author Affiliations
1Parkinson’s Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania
2Mental Illness Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania
3Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
4Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
5Department of Veterans Affairs, Health Services Research and Development, Center for Clinical Management Research, Ann Arbor, Michigan
6Center for Statistical Consultation and Research, University of Michigan, Ann Arbor
7Morton and Gloria Shulman Movement Disorder Centre, The Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
8Geriatric Research, Education and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
9Department of Psychiatry, University of Michigan, Ann Arbor
JAMA Neurol. 2016;73(5):535-541. doi:10.1001/jamaneurol.2016.0031.
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Importance  As many as 60% of patients with Parkinson disease (PD) experience psychosis, 80% develop dementia, and the use of antipsychotics (APs) in the population with PD is common. The use of APs by patients with dementia in the general population is associated with increased mortality, but whether this risk extends to patients with PD remains unknown.

Objective  To determine whether AP use in patients with PD is associated with increased mortality.

Design, Setting, and Participants  This retrospective matched-cohort study used data from a Veterans Health Administration database from fiscal years 1999 to 2010 to examine the risk associated with AP use in a cohort of patients with idiopathic PD and recent stable physical health. The rates of 180-day mortality were compared in 7877 patients initiating AP therapy and 7877 patients who did not initiate AP therapy (matched for age ±2.5 years, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new nonpsychiatric medications). Data were analyzed from October 19, 2012, to September 21, 2015.

Main Outcomes and Measures  Mortality rates at 180 days in those patients who initiated AP therapy compared with matched patients who did not use APs. Cox proportional hazards regression models were used with intent-to-treat (ITT) and exposure-only analyses.

Results  The study population included 7877 matched pairs of patients with PD (65 women [0.8%] and 7812 men [99.2%] in each cohort; mean [SD] age, 76.3 [7.7] years for those who initiated AP therapy and 76.4 [7.6] years for those who did not). Antipsychotic use was associated with more than twice the hazard ratio (HR) of death compared with nonuse (ITT HR, 2.35; 95% CI, 2.08-2.66; P < .001). The HR was significantly higher for patients who used typical vs atypical APs (ITT HR, 1.54; 95% CI, 1.24-1.91; P < .001). Among the atypical APs used, HRs relative to nonuse of APs in descending order were 2.79 (95% CI, 1.97-3.96) for olanzapine, 2.46 (95% CI, 1.94-3.12) for risperidone, and 2.16 (95% CI, 1.88-2.48) for quetiapine fumarate.

Conclusions and Relevance  Use of APs is associated with a significantly increased mortality risk in patients with PD, after adjusting for measurable confounders. This finding highlights the need for cautious use of APs in patients with PD. Future studies should examine the role of nonpharmacologic strategies in managing psychosis in PD. In addition, new pharmacologic treatments that do not increase mortality in patients with neurodegenerative diseases need to be developed.

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Figure.
Mortality Rates in Antipsychotic (AP)-Exposed vs Non–AP-Exposed Patients

Covariate-adjusted 180-day survival estimates by baseline AP treatment status (intention-to-treat analysis) are shown. Graph is based on Cox proportional hazards regression modeling without pairing.

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