Antipsychotics Boost Pneumonia Risk in Alzheimer's Patients

Megan Brooks

September 01, 2016

Antipsychotic medications raise the risk for pneumonia in patients with (and without) Alzheimer's disease (AD), a large Finnish study confirms.

The risk is highest at the start of antipsychotic treatment but remains increased with long-term use. There are no marked differences in risk between the most commonly used antipsychotic drugs: quetiapine (Seroquel, AstraZeneca Pharmaceuticals), risperidone (Risperdal, Johnson & Johnson), and haloperidol (Haldol, Janssen Pharmaceuticals), the study team found.

"The risk increase per se is nothing new, as the FDA [US Food and Drug Administration] issued a warning about the use of antipsychotics for behavioral and psychological symptoms of dementia already in 2005, and pneumonia was listed as one of the leading causes of death already in that report," first author Anna-Maija Tolppanen, PhD, from the University of Eastern Finland in Kuopio, told Medscape Medical News.

"What our study adds to the literature is the comparison between individual antipsychotics, as studies on the comparative safety have been relatively rare. In addition, we were able to find only one published study that had assessed this association specifically in persons with Alzheimer's disease [prior to this study]," she explained.

The study was published online August 30 in Chest.

"The findings support current treatment guidelines on setting a high threshold for initiating antipsychotic use among persons with Alzheimer's disease, and also the risks and benefits should be weighted carefully," Dr Tolppanen said. "If antipsychotic use is initiated, the duration should be limited, as the risk of pneumonia, as well as the risk of other adverse outcomes, does not disappear with long-term use."

The Finnish MEDALZ Study

The researchers used the Medication and Alzheimer's disease (MEDALZ) cohort to assess the association between antipsychotic medication and hospitalization or death due to pneumonia. The cohort included 60,584 community-dwelling adults diagnosed with AD from 2005 to 2011, including 12,225 incident pneumonia cases. For comparison, the investigators selected a matched cohort of 60,584 patients without AD, among whom there were 6195 incident pneumonia cases.

Antipsychotic use was associated with increased pneumonia risk in both AD and non-AD cohorts. In the AD cohort, antipsychotic users had a twofold relative risk for pneumonia after adjusting for confounders (propensity score adjusted hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.90 - 2.13). The association was stronger in the non-AD cohort (adjusted HR, 3.43; 95% CI, 2.99 - 3.93).

In both cohorts, antipsychotic use was consistently associated with higher pneumonia risk in all age groups, but the associations were strongest in the youngest group (those aged 34 to 74 years). Patients with the shortest duration of use had the highest relative risk increase, but the risk was not attenuated with long-term use. There were no marked differences in risk with quetiapine, risperidone, and haloperidol.

"With observational data we cannot fully rule out a shared causality between pneumonia and antipsychotic use, but the risk-benefit balance should be considered when antipsychotics are prescribed," Dr Tolppanen and colleagues conclude.

The study had no funding. Dr Tolppanen has disclosed no relevant financial relationships. Three coauthors report having financial relationships with various pharmaceutical companies, as listed in the original article.

Chest. Published online August 30, 2016. Abstract

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