clozapine and Pneumonia--Aspiration

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

Topics: Agammaglobulinemia; Antipsychotic Agents; Betacoronavirus; Clozapine; Contraindications, Drug; Coronavirus Infections; COVID-19; Drug Monitoring; Drug Prescriptions; Humans; Pandemics; Parkinson Disease; Pneumonia, Aspiration; Pneumonia, Viral; Psychotic Disorders; SARS-CoV-2; Schizophrenia; Sialorrhea

Clozapine-induced gastric hypomotility (CIGH) is an underreported, underrecognized effect from high-dose clozapine. In this report, we present a patient with treatment refractory schizophrenia receiving high-dose clozapine who aspirated during general anesthesia for electroconvulsive therapy. To our knowledge, this is the first report of aspiration under general anesthesia as a result of CIGH and highlights the potential dangers high-dose clozapine can pose on patients undergoing electroconvulsive therapy with unrecognized CIGH.

Topics: Anesthesia, General; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Gastrointestinal Motility; Humans; Male; Pneumonia, Aspiration; Stomach; Young Adult

Side Effects of Smoking Cessation Abstract. We present the case of a clozapine intoxication associated with aspiration pneumonia due to smoking cessation. Clozapine is mainly metabolized by CYP1A2. CYP1A2 is induced by cigarette smoking, which may change the plasma level of clozapine, especially if consuming habits change.. Zusammenfassung. Wir präsentieren den Fall einer Clozapin-Intoxikation mit konsekutiver Aspirationspneumonie nach einem Rauchstopp. Clozapin wird hauptsächlich über CYP1A2 metabolisiert, Zigarettenkonsum führt zu einer Induktion von CYP1A2 und kann hierdurch den Plasmaspiegel von Clozapin relevant beeinflussen, insbesondere, wenn sich die Konsumgewohnheiten ändern.

Topics: Clozapine; Confusion; Cytochrome P-450 CYP2A6; Humans; Male; Middle Aged; Pneumonia, Aspiration; Risk Factors; Schizophrenia, Paranoid; Sialorrhea; Smoking Cessation

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pneumonia, Aspiration; Schizophrenia, Paranoid; Sialorrhea

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Pneumonia, Aspiration; Risk Factors; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Pneumonia, Aspiration; Pulmonary Embolism; Schizophrenia

Topics: Adult; Antipsychotic Agents; Citalopram; Clozapine; Humans; Male; Pneumonia, Aspiration; Schizophrenia, Paranoid

Experience with managing overdoses of the atypical antipsychotic agent, clozapine, has been limited. A 20-year-old woman, who presented 6 h after ingesting 3500 mg of clozapine, had an unexpectedly prolonged duration of tachycardia and somnolence. Successful recovery followed management with supportive measures for several days in the intensive care unit. However, the duration of symptoms greatly exceeded that predicted by the published 12-h half-life of clozapine and was associated with an unexplained persistence of serum clozapine concentrations. Recovery with normalization of autonomic function occurred only after serum clozapine began to decline again after a 4-day plateau, as revealed by serum monitoring. Similar observations have been reported in two other cases. In overdose, clozapine may not behave as predicted by its published pharmacokinetics. Persistent serum drug concentrations may prolong the period of intensive care, suggesting that aggressive measures to remove clozapine from the gut at the time of overdose may be warranted.

Topics: Adult; Anti-Bacterial Agents; Clozapine; Drug Overdose; Female; Humans; Intubation, Intratracheal; Pneumonia, Aspiration; Pneumonia, Staphylococcal; Staphylococcus aureus; Treatment Outcome

Topics: Aged; Antipsychotic Agents; Clozapine; Conscious Sedation; Drug Overdose; Female; Humans; Pneumonia, Aspiration; Seizures

Topics: Antipsychotic Agents; Clozapine; Constipation; Death, Sudden; Drug Therapy, Combination; Fecal Impaction; Humans; Male; Middle Aged; Pneumonia, Aspiration; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Middle Aged; Pneumonia, Aspiration; Sialorrhea