A study published in the American Journal of Geriatric Psychiatry found that inappropriate use of atypical antipsychotic (AAP) agents in older patients with Parkinson disease (PD) is associated with an increase in all-cause mortality, primarily caused by pneumonia. In long-term care facilities, the rate of antipsychotic use in patients with PD ranges from 15% to 30%; however, the efficacy of AAPs in these patients has not been evaluated in large clinical trials.

Except for aripiprazole, quetiapine, and clozapine, the American Geriatric Society does not recommend the use of antipsychotic medications in PD given the risk of worsening movement symptoms. In patients with PD, antipsychotics can impair swallowing and increase the risk of aspiration pneumonia, a leading cause of death in PD patients.

Farid Chekani MD, PhD, of the College of Pharmacy, University of Houston, Texas, and colleagues retrospectively analyzed Medicare data from 2007 to 2010 using a propensity-matched approach to determine the risk of all-cause mortality in patients with PD receiving inappropriate AAPs. Patients with schizophrenia and bipolar disorder were excluded, although all patients had a diagnosis of comorbid depression. Inappropriate AAPs included olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, and ziprasidone.

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During a 6-month follow-up period, among patients in the appropriate AAP group (n=6038), the all-cause mortality rate was 15.65%, whereas in the inappropriate AAP group (n=6038), the rate was 16.91%. Patients with PD who used inappropriate AAPs had an increased risk of all-cause mortality compared with those using appropriate AAPs (hazard ratio [HR], 1.13; 95% CI, 1.01-1.28). Compared with quetiapine, risperidone was associated with a higher risk of death (HR, 1.20; 95% CI, 1.03-1.40) in sensitivity analysis. All analyses showed a significant relationship between death and pneumonia, which functioned as a mediator with AAP use.

The study had a number of limitations, including the use of secondary data sources, which may be subject to undercoding and improper coding. Pharmacy data provided information on drugs prescribed and refills but could not determine if the patient had taken the medication.

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The study authors concluded, “This study provided evidence regarding the risk of mortality due to inappropriate antipsychotic use which is mainly mediated by pneumonia in older patients with PD. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.”

Disclosure: A study author reported conflicts of interest in this work. See the original paper for a full list of disclosures.


Chekani F, Holmes HM, Johnson ML, Chen H, Sherer JR, Aparasu RR. Risk of mortality associated with atypical antipsychotic use: a national cohort study of older adults with depression and Parkinson’s disease. Am J Geriatr Psychiatry. 2020. doi: 10.1016/j.jagp.2020.01.193