Antipsychotic Drug Use and Community-Acquired Pneumonia

Department of Medical Informatics, Erasmus University Medical Center, Dr Molewaterplein 50, 3000 DR, Rotterdam, The Netherlands, .
Current Infectious Disease Reports (Impact Factor: 1.68). 03/2011; 13(3):262-8. DOI: 10.1007/s11908-011-0175-y
Source: PubMed


Antipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psychiatric disorders. In April 2005, the US Food and Drug Administration issued a warning about the increased risk of all-cause mortality associated with atypical antipsychotic use in elderly patients with dementia. Pneumonia was one of the most frequently reported causes of death. The same warning was extended to typical antipsychotics in June 2008. In recent years, several observational studies have further explored the association between antipsychotic use, mainly in elderly patients, and the risk of fatal/nonfatal community-acquired pneumonia. The aim of this review is to revise and discuss the scientific evidence and biologic explanations for the association between atypical and typical antipsychotic use and pneumonia occurrence. Some general recommendations to clinicians are proposed to prevent the risk of pneumonia in patients requiring antipsychotic treatment.

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Available from: Gianluca Trifirò, Mar 21, 2014
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    ABSTRACT: This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33 024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics.
    Schizophrenia Bulletin 01/2012; 39(3). DOI:10.1093/schbul/sbr202 · 8.45 Impact Factor
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    ABSTRACT: Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients. We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics. Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk than atypical antipsychotics, while the risk of pneumonia was similar between the classes. Choice of observational study design is critical in studying the adverse effects of antispychotics. Cohort and instrumental variable analyses gave more consistent results to clinical studies for mortality outcomes as have self-controlled case-series for the risk of cerebrovascular events and stroke. Observational evidence has highlighted the potential for antipsychotics to be associated with serious adverse events that were not reported in RCTs including hip fracture and pneumonia. Good quality observational studies are required, that employ appropriate study designs that are robust towards unmeasured confounding, to confirm the potential excess risk of hip fracture and pneumonia with antipsychotics.
    BMC Medical Research Methodology 06/2012; 12(1):72. DOI:10.1186/1471-2288-12-72 · 2.27 Impact Factor
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    ABSTRACT: BACKGROUND:Antipsychotic medications are extensively used in nursing homes for management of behavioral and psychiatric disorders in the elderly. Prior research suggests that pneumonia is one of the common causes of antipsychotic-related mortality in this population. None of the studies compared typical and atypical antipsychotics with respect to pneumonia.OBJECTIVE:To examine the risk of pneumonia with use of typical versus atypical antipsychotics in dual eligible elderly nursing home residents.METHODS:The study involved a retrospective cohort design matched on propensity score using Medicare and Medicaid Analytical eXtract data from 4 US states. The study population included all elderly dual eligible (Medicaid and Medicare) nursing home residents (aged≥65 years) who initiated antipsychotics any time between July 1, 2001, and December 31, 2003. The risk of pneumonia during the 6-month follow-up period was modeled using a Cox proportional model and extended Cox hazard model stratified on matched pairs based on propensity score, using atypical agents as the reference category.RESULTS:Analysis of Medicaid-Medicare data revealed that there were 49,904 new antipsychotic (46,293 atypical and 3611 typical) users in the unmatched cohort and 7218 (3609 atypical and 3609 typical) users in the matched cohort. The unadjusted rate of pneumonia was 8.17% (4.61 events per person year) for atypical users and 5.21% (5.21 events per person year) for typical users. The RESULTS: HR 1.17, 95% CI 0.83-1.66; and 50-180 days: HR 1.36, 95% CI 0.87-2.14) suggest that there was no significant difference in the risk of pneumonia among typical and atypical users.CONCLUSIONS:The study found no differential risk of pneumonia between typical versus atypical antipsychotic use in dual eligible nursing home residents. Given the differential risk of mortality with typical and atypical antipsychotic use in nursing homes, more research is needed to evaluate other contributory factors of mortality with respect to these 2 antipsychotic classes.
    Annals of Pharmacotherapy 04/2013; 47(4). DOI:10.1345/aph.1R510 · 2.06 Impact Factor
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