High doses of specific antipsychotics are associated with an increased risk of pneumonia in patients with schizophrenia, according to a recent study published in JAMA Psychiatry.
Researchers examined the association between antipsychotic use and pneumonia risk in patients with schizophrenia. The study followed 61,889 Finnish patients with schizophrenia (mean age 46.2 years, 50.3% men) from 1996 to 2017, assessing the impact of antipsychotic dosing, anticholinergic burden, and monotherapy versus polytherapy on pneumonia risk. Antipsychotic use was categorized by dose—low (<0.6 defined daily dose [DDD]), medium (0.6-<1.1 DDD), and high (≥1.1 DDD)—according to the World Health Organization's DDD.
Over 22 years of follow-up, 14.4% of the cohort experienced at least one pneumonia-related hospitalization. Using within-individual Cox proportional hazards regression models, the study found that the use of any antipsychotic was not linked to an increased risk of pneumonia (adjusted hazard ratio [AHR], 1.12; 95% confidence interval [CI], 0.99-1.26). When compared to no antipsychotic use, both low-dose (AHR, 1.00; 95% CI, 0.88-1.15) and medium-dose antipsychotic use (AHR, 1.10; 95% CI, 0.96-1.26) were not associated with pneumonia risk. However, high-dose antipsychotic use was associated with an increased risk (AHR, 1.20; 95% CI, 1.06-1.37; P = .005).
Results showed that antipsychotics with a high anticholinergic burden were linked to an increased incidence of pneumonia. Compared with no antipsychotic use, monotherapy was associated with an increased pneumonia risk (AHR, 1.15; 95% CI, 1.02-1.30; P = .03) in a dose-dependent manner, while polytherapy was not. Only antipsychotics with high anticholinergic burden were associated with increased risk (AHR, 1.26; 95% CI, 1.10-1.45; P < .001).
None of the first-generation antipsychotics were linked to an increased risk of pneumonia, while some high-dose second-generation antipsychotics showed an association. Of the specific agents, high-dose quetiapine showed a notable association (AHR, 1.78; 95% CI, 1.22-2.60; P = .003), followed by high- and medium-dose clozapine, and high-dose olanzapine.
Clozapine at both high and medium doses (≥180 mg/d) was associated with pneumonia, with AHRs of 1.44 (95% CI, 1.22-1.71) and 1.43 (95% CI, 1.18-1.74), respectively (P < .001). Olanzapine at high doses (≥11 mg/d) was associated with an increased risk of pneumonia (AHR, 1.29; 95% CI, 1.05-1.58; P = .02). Within 30 days of being admitted for pneumonia, 1,137 patients (12.8%) died.
The study adjusted for several factors, including age, concomitant use of other psychotropic drugs, and a modified pneumonia severity index. Sensitivity analyses were conducted, adjusting for chronic obstructive pulmonary disease and anticholinergic burden from other medications.
The researchers suggest monitoring eating habits and examining swallowing capacity in at-risk patients as potential prevention strategies. However, they note limitations such as the possibility of residual confounding and the inability to include cases of pneumonia not requiring admission.
Full disclosures can be found in the published study.
