Antipsychotic medication exposure, clozapine, and pneumonia: results from a self‐controlled study

Abstract

medication exposure, clozapine, and pneumonia: results from a self-controlled study. Objective: By using a self-controlled design, we investigated whether antipsychotic medication exposure was associated with increased pneumonia risk and whether patients receiving clozapine were more likely to develop pneumonia than patients receiving other antipsychotic medications. Methods: Through nationwide health registers, we identified all outpatients with schizophrenia initiating antipsychotic treatment. First, we estimated whether antipsychotic-na€ ıve patients with schizophrenia increased their risk of pneumonia after initiation of either a first-or second-generation antipsychotic medication using a one-year mirrorimage model. Afterward, similar analyses were made for individual second-generation antipsychotics. Lastly, the rate of pneumonia for patients initiated on clozapine was compared to patients commenced on other second-generation antipsychotics. Results: In total, 8355 antipsychotic-na€ ıve patients with schizophrenia were initiated on a first-generation antipsychotic medication; 0.95% of the patients had developed pneumonia before exposure, compared to 0.68% after exposure (P = 0.057). Similar findings were made for the 8001 antipsychotic-na€ ıve patients with schizophrenia initiated on second-generation antipsychotic medications, with 0.56% developing pneumonia before exposure compared to 0.55% after exposure (P = 1.00). Second-generation antipsychotic medications did not increase the pneumonia risk, except for risperidone (increased by 0.32%; P = 0.007) and clozapine, which gave the largest absolute increase in pneumonia risk although not significant (increased by 0.64%; P = 0.10). The rate of pneumonia was higher after initiation of clozapine than for other second-generation antipsychotic medications. Conclusion: Most antipsychotic medications were not found to increase the risk of pneumonia. Clozapine exposure might be associated with increased risk of developing pneumonia.

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

“…Despite the fact that clozapine is not indicated for dementia, its package insert was modified, too. The association between clozapine and pneumonia is supported by data from the Taiwan registry [37], other studies previously reviewed [49], and further verified by a mirror-image study in the Danish registry [157].…”

“…The lethality of pneumonia in clozapine patients is explained in that clozapine can contribute to pneumonia, and once pneumonia develops it can cause a clozapine intoxication; therefore, the combination of pneumonia and clozapine intoxication is highly lethal. This complex bidirectional association [162] is described in detail in online supplementary Box S7 [157,[163][164][165][166][167][168][169]. Our recommendations for decreasing the risk and lethality of pneumonia in clozapine patients are described in online supplementary Box S8 [65,162,170,171].…”

Clozapine is strongly associated with the risk of pneumonia and inflammation

“…Therefore, the contributing effects of the severity level of mental illness on pneumonia needs to be further explored by future studies in clozapine patients. On the other hand, clozapine has specific effects independent of the greater severity of illness in the clozapine patients, since using mirror-image design in the Danish registry,Rhode et al 29 Rhode et al 29 found that clozapine gave the largest absolute increase in pneumonia risk although it did not reach significance, probably due to the relatively small sample size. In the year before clozapine, there were 1.22% (23/1872) patients with pneumonia and in the first year 1.87% (35/1872).…”

Pneumonia risk: approximately one‐third is due to clozapine and two‐thirds is due to treatment‐resistant schizophrenia

“…This includes 79 pneumonia cases in 8355 patients who were naïve and started a first-generation antipsychotic, and 45 pneumonia cases in 8001 patients who were naïve and started a second-generation antipsychotic (5). article (5) described the following pneumonia rates over approximately 1 year: (i) 0.946% in 8355 antipsychotic-na€ ıve patients versus 0.682% after the first year of schizophrenia when treated with first-generation antipsychotics and (ii) 0.562% in another 8001 antipsychotic-na€ ıve patients versus 0.550% after the first year of schizophrenia when treated with second-generation antipsychotics.…”