Antipsychotic Drug Use and Risk of Pneumonia in Elderly People

Knol, Wilma; Marum, Rob J. van; Jansen, Paul A. F.; Souverein, Patrick C.; Schobben, A. F. A. M.; Egberts, Toine C. G.

doi:10.1111/j.1532-5415.2007.01625.x

Cited by 172 publications

(178 citation statements)

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“…The higher rate of chest infections after prescription of atypical antipsychotics is in line with Knol et al's study, 7 where a stronger association between atypical antipsychotics and pneumonia was also seen, as compared with conventional antipsychotics. Users of conventional antipsychotics had a higher risk of death from infections, including pneumonia, than users of atypical antipsychotics in Setoguchi et al's study, 4 but the difference was not statistically significant.…”

Section: Comparison With Existing Literaturesupporting

confidence: 79%

“…6 Older patients currently using antipsychotic medicines, when compared with those not currently using them, were noted to be at higher risk for pneumonia with an adjusted odds ratio of 1.6 (95% confidence interval [CI] = 1.3 to 2.1) in a nested case control study on pharmacy dispensing and hospital discharge registrations. 7 Users of atypical antipsychotics showed a higher risk for pneumonia than users of conventional antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

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Pneumonia following antipsychotic prescriptions in electronic health records: a patient safety concern?

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Meyboom³

et al. 2010

Br J Gen Pract

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Section: Comparison With Existing Literaturesupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Pneumonia following antipsychotic prescriptions in electronic health records: a patient safety concern?

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Meyboom³

et al. 2010

Br J Gen Pract

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“…In addition, frail elderly persons may experience delirium as a prodromal symptom of pneumonia and, as a consequence, receive antipsychotic treatment. This increases the risk of protopathic bias in observational studies, that is, wrong attribution of the onset of pneumonia to antipsychotic administration [4]. Nevertheless, Trifirò et al [5] and Huybrechts et al [7] observed that the risk of pneumonia appears to be dose-dependent, strengthening the hypothesis that antipsychotics are involved in the causal pathway.…”

mentioning

confidence: 93%

“…Three studies demonstrated that the risk of pneumonia varies by antipsychotic class, with a higher risk being attributed to atypical antipsychotics [4,[6][7][8][9]. A more recent finding is the demonstration of a differential risk associated with individual antipsychotic drugs [5,7].…”

Section: Expert Opinionmentioning

confidence: 99%

“…After the initial warning, several observational studies have investigated the association between antipsychotics use in elderly patients and pneumonia ( Table 1). In the Netherlands, Knol et al assessed the risk of pneumonia leading to hospitalization using a record-linkage administrative database [4], while Trifirò et al investigated fatal and nonfatal pneumonia using a nationwide general practice database [5]. Interestingly, both studies found an increased risk of pneumonia with antipsychotic use, although twice as high with atypical as compared to conventional antipsychotic agents.…”

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Antipsychotic use in elderly patients and the risk of pneumonia

Gambassi

Sultana

Trifirò

2014

Expert Opinion on Drug Safety

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Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia

Luykx,

Correll,

Manu

et al. 2024

JAMA Psychiatry

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ImportanceAntipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia.ObjectiveTo estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia.Design, Setting, and ParticipantsThis cohort study identified patients with schizophrenia or schizoaffective disorder (hereafter, schizophrenia) aged 16 years or older from nationwide Finnish registers from 1972 to 2014. Data on diagnoses, inpatient care, and specialized outpatient care were obtained from the Hospital Discharge Register. Information on outpatient medication dispensing was obtained from the Prescription Register. Study follow-up was from 1996 to 2017. Data were analyzed from November 4, 2022, to December 5, 2023.ExposuresUse of specific antipsychotic monotherapies; antipsychotics modeled by dosage as low (&lt;0.6 of the World Health Organization defined daily dose [DDD] per day), medium (0.6 to &lt;1.1 DDDs per day), or high dose (≥1.1 DDDs per day); antipsychotic polypharmacy; and antipsychotics categorized according to their anticholinergic burden as low, medium, and high.Main Outcomes and MeasuresThe primary outcome was hospitalization for incident pneumonia. Pneumonia risk was analyzed using adjusted, within-individual Cox proportional hazards regression models, with no antipsychotic use as the reference.ResultsThe study included 61 889 persons with schizophrenia (mean [SD] age, 46.2 [16.0] years; 31 104 men [50.3%]). During 22 years of follow-up, 8917 patients (14.4%) had 1 or more hospitalizations for pneumonia and 1137 (12.8%) died within 30 days of admission. Compared with no antipsychotic use, any antipsychotic use overall was not associated with pneumonia (adjusted hazard ratio [AHR], 1.12; 95% CI, 0.99-1.26). Monotherapy use was associated with increased pneumonia risk compared with no antipsychotic use (AHR, 1.15 [95% CI, 1.02-1.30]; P = .03) in a dose-dependent manner, but polytherapy use was not. When categorized by anticholinergic burden, only the use of antipsychotics with a high anticholinergic burden was associated with pneumonia (AHR, 1.26 [95% CI, 1.10-1.45]; P &lt; .001). Of specific drugs, high-dose quetiapine (AHR, 1.78 [95% CI, 1.22-2.60]; P = .003), high- and medium-dose clozapine (AHR, 1.44 [95% CI, 1.22-1.71]; P &lt; .001 and AHR, 1.43 [95% CI, 1.18-1.74]; P &lt; .001, respectively), and high-dose olanzapine (AHR, 1.29 [95% CI, 1.05-1.58]; P = .02) were associated with increased pneumonia risk.Conclusions and RelevanceResults of this cohort study suggest that in patients with schizophrenia, antipsychotic agents associated with pneumonia include not only clozapine (at dosages ≥180 mg/d) but also quetiapine (≥440 mg/d) and olanzapine (≥11 mg/d). Moreover, monotherapy antipsychotics and antipsychotics with high anticholinergic burden are associated with increased pneumonia risk in a dose-dependent manner. These findings call for prevention strategies aimed at patients with schizophrenia requiring high-risk antipsychotics.

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Antipsychotic Drug Use and Risk of Pneumonia in Elderly People

Abstract: Use of antipsychotics in elderly people is associated with greater risk of pneumonia. This risk is highest shortly after the initiation of treatment, with the greatest increase in risk found for atypical antipsychotics.

Cited by 172 publications

References 34 publications

Pneumonia following antipsychotic prescriptions in electronic health records: a patient safety concern?

Pneumonia following antipsychotic prescriptions in electronic health records: a patient safety concern?

Antipsychotic use in elderly patients and the risk of pneumonia

Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia

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