Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson's Disease

Abstract

ObjectivesThis study examined the risk of all-cause-mortality in patients with Parkinson's Disease (PD) and comorbid depression using inappropriate atypical antipsychotics (AAPs), based on the 2015 American Geriatrics Society Beers criteria. MethodsA retrospective analysis of 2007–2010 Minimum Data Set linked Medicare data was conducted using a propensity-matched approach. The cohort included PD patients aged 65 years or older without schizophrenia or bipolar disorder who started AAPs. All patients had a diagnosis of comorbid depression. Risk of 6-month all-cause-mortality was compared across appropriate AAPs (aripiprazole, clozapine, or quetiapine) and inappropriate AAPs (olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone) using robust Cox regression models involving the matched cohort. ResultsAll-cause mortality rate was 15.65% in appropriate AAP group (n = 6,038) and 16.91% in inappropriate AAP group (n = 6,038) over 6-month follow-up in the matched cohort. The robust Cox proportional hazards models revealed increased risk of all-cause mortality (hazard ratio [HR] 1.13 [95% confidence interval {CI}: 1.01–1.28)] for patients who used inappropriate compared to appropriate AAPs. Risk of death was also higher for risperidone compared to quetiapine (HR: 1.20 [95% CI: 1.03–1.40]) in sensitivity analysis. However, there was a significant relationship between pneumonia and death in all analyses. The impact of inappropriate AAP use on mortality was not significant when pneumonia was modeled as a mediator. ConclusionsInappropriate AAP use is associated with a higher risk of all-cause-mortality in older patients with PD which is mainly mediated by pneumonia. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.