Atypical Antipsychotic Medications Increase Pneumonia Risk in Elderly

January 5, 2016 Inovalon

By Sandhya Mehta, Zulkarnain Pulungan, Barton T. Jones and Christie Teigland


The use of second-generation (i.e., atypical) antipsychotic drugs has rapidly expanded in the past decade due to superior tolerability and efficacy compared to conventional (i.e., typical) antipsychotics. From 1996 to 2004 the number of atypical antipsychotic medications prescribed in the elderly increased from 15% to 73%. This upsurge has revealed several safety alerts, the most alarming being the increased risk of mortality with specific cause of death being heart related events and infection (pneumonia in particular). In fact, the FDA issued a black box warning in 2005 indicating increased risk of death in atypical users and extended the warning to typical antipsychotic users in 2008.

In 2014, the Statistical Research Department of Inovalon examined increased incidence of pneumonia in elderly patients taking individual antipsychotic medications, which had not previously been studied.

Initial Assumptions

Before the Inovalon study, the available evidence had evaluated the increased risk of pneumonia with antipsychotics use compared with nonuse overall, and indicated that higher risk can be attributed to atypical compared to typical antipsychotics. However, these studies did not have sufficient data to compare the risk of individual antipsychotic medications. Previous researchers hypothesized that risk of pneumonia may differ by individual antipsychotic drug, because of relevant differences in the receptor binding profile of the various medications. They emphasized the need to examine the risk of individual drugs.

Study Design

The Inovalon retrospective study employed a multiple propensity score adjusted survival model to determine which atypical antipsychotic medication posed the greatest risk of pneumonia in elderly patients within one year after starting the drug. A seven-step approach was used to balance measured risk factors for the outcomes between different groups.

The source of the patient data was the Inovalon MORE2 Registry®, a statistically de-identified data warehouse that includes more than 10 billion medical events and longitudinal patient-level data of more than 127 million unique patients from a broad range of data sources in a variety of healthcare settings and specialties throughout the United States. The characteristics examined included: age, gender, race/ethnicity, and comprehensive information on diseases/diagnoses, chronic conditions, and medical and pharmacy utilization.

Study Population

The study analyzed pharmacy and medical claims data for 92,234 Medicare Advantage beneficiaries, age 65 and older, who had been newly prescribed an atypical antipsychotic within the period of July 2005 to June 2011.  To evaluate the incidence of pneumonia, the patients were followed for one year or until they changed antipsychotic medication, discontinued health coverage or died, whichever occurred first.

The study evaluated the following atypical antipsychotics most often prescribed for the elderly subjects in the study population: Quetiapine, Risperidone, Olanzapine, Aripiprazole and Ziprasidone.

Study Findings

Atypical Antipsychotics

Of the 92,234 patients examined, 12,411 or 13.46% were diagnosed with pneumonia within one year after initiation of the atypical antipsychotic drug. Quetiapine was used as the reference group because it was prescribed more than any other atypical antipsychotic (45.3% of the patients in the study population). The analysis found that compared to patients taking Quetiapine, Risperidone users have a 14% higher risk of getting pneumonia and Olanzapine users have a 10% higher risk. No substantial difference was found between Quetiapine and other atypical antipsychotics.

Call to Action

Clinicians should consider the relative safety of these drugs in selecting the most appropriate medication for elderly patients, who are at high risk for developing pneumonia. They need to carefully weigh the potential risks and benefits for the patient and closely monitor all elderly patients treated with atypical antipsychotic drugs for increased risk and incidence of pneumonia.

The full article “Comparative safety of atypical antipsychotics and the risk of pneumonia in the elderly” can be found in Pharmacoepidemiology and Drug Safety (2015), Volume 24, p. 1271. If you have questions, please contact Dr. Christie Teigland at

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