olanzapine and Pneumonia

There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia-related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia-related death with specific antipsychotic exposure.. Deaths analysed were those reported to a UK-based drug-related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case-control study with cases defined as pneumonia-related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post-mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders.. There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia-related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15-1·55]; prescribed AOR 1·28 [95% CI 1·11-1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77-1·47]; prescribed AOR 0·91 [95% CI 0·71-1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22-1·82]; prescribed AOR 1·44 [95% CI 1·18-1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07-1·66]; prescribed AOR 1·28 [95% CI 1·01-1·64]).. Olanzapine and quetiapine were found to increase the risk of pneumonia-related death in this NPSAD sample to a clinically important extent.

Topics: Antipsychotic Agents; Case-Control Studies; Humans; Olanzapine; Pneumonia; Quetiapine Fumarate; United Kingdom

An association between antipsychotic drugs and pneumonia has been demonstrated in several studies; however, the risk for pneumonia caused by specific antipsychotics has not been extensively studied. The underlying mechanism is still unknown, and several receptor mechanisms have been proposed. Therefore, using a combined pharmacovigilance-pharmacodynamic approach, we aimed to investigate safety signals of US Food and Drug Administration (FDA)-approved antipsychotics for reporting pneumonia and the potential receptor mechanisms involved. A disproportionality analysis was performed to detect a signal for reporting "infective-pneumonia" and "pneumonia-aspiration" and antipsychotics using reports submitted between 2004 and 2019 to the FDA adverse events spontaneous reporting system (FAERS) database. Disproportionality was estimated using the crude and the adjusted reporting odds ratio (aROR) and its 95% confidence interval (CI) in a multivariable logistic regression. Linear regressions investigated the relationship between aROR and receptor occupancy, which was estimated using in vitro receptor-binding profiles. Safety signals for reporting infective-pneumonia were identified for clozapine (LL = 95% 3.4, n = 546 [aROR: 4.8]) as well as olanzapine (LL = 95% 1.5, n = 250 [aROR: 2.1]) compared with haloperidol, while aRORs were associated with higher occupancies of muscarinic receptors (beta = .125, P-value = .016), yet other anti-muscarinic drugs were not included as potential confounders. No safety signals for reporting pneumonia-aspiration were detected for individual antipsychotics. Multiple antipsychotic use was associated with both reporting infective-pneumonia (LL 95%: 1.1, n = 369 [aROR:1.2]) and pneumonia-aspiration (LL 95%: 1.7, n = 194 [aROR: 2.0]). Considering the limitations of disproportionality analysis, further pharmacovigilance data and clinical causality assessment are needed to validate this safety signal.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pharmacovigilance; Pneumonia; Pneumonia, Aspiration; Receptors, Muscarinic; United States; United States Food and Drug Administration; Young Adult

Like mood stabilizers, most second-generation antipsychotics are widely used to treat patients with bipolar disorder, yet their safety is still a concern. This study explored the association between antipsychotics and mood stabilizers and the risk of pneumonia, and it provides evidence-based information for clinical practice.. In a nationwide cohort of bipolar patients (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81, and 296.89) derived from the National Health Insurance Research Database in Taiwan, who were admitted between July 1, 1998, and December 31, 2006 (N = 9,999), we identified 571 patients who developed pneumonia (ICD-9 codes 480 to 486 and 507) requiring hospitalization defined as cases. On the basis of risk-set sampling in a 1:4 ratio, 2,277 matched controls were selected from the same cohort. We used conditional logistic regression to assess the association between drug exposure and pneumonia and sensitivity analyses to validate the association.. Current use of several antipsychotics separately, including olanzapine (adjusted risk ratio [RR] = 2.97, P < .001), clozapine (RR = 2.59, P < .01), and haloperidol (RR = 3.68, P < .001), is associated with a dose-dependent increase in the risk of pneumonia. Interestingly, lithium has a dose-dependent protective effect from pneumonia. Among certain drug combinations, olanzapine plus carbamazepine had the highest risk (RR = 11.88, P < .01), followed by clozapine plus valproic acid (RR = 4.80, P < .001).. Several antipsychotics, but not mood stabilizers, were associated with the risk of pneumonia, which deserves our concern regarding patient safety. Some of the combinations of therapy resulted in synergy of risk.

Topics: Adolescent; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Case-Control Studies; Clozapine; Cohort Studies; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Female; Hospitalization; Humans; Lithium Carbonate; Male; Middle Aged; Multivariate Analysis; Olanzapine; Pneumonia; Propensity Score; Risk Factors; Taiwan; Valproic Acid; Young Adult

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.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Clozapine; Cohort Studies; Dibenzothiazepines; Dibenzothiepins; Drug Therapy, Combination; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Pneumonia; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Sulpiride; Taiwan