clozapine and Bacterial-Infections

To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes.. Three patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alternative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined.. Clozapine toxicity may manifest with multiple symptoms, including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well characterized, thus careful monitoring is required for medically ill patients receiving clozapine. Clozapine is extensively bound to the acute phase reactant, α-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation.. Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine.

Topics: Antipsychotic Agents; Bacterial Infections; Clozapine; Critical Care; Female; Humans; Inflammation; Male; Middle Aged; Schizophrenia

A retrospective chart review of hospitalized patients was completed to verify whether there were differences in the prescription rate of antibiotics to patients treated with clozapine. Subjects were inpatients with a diagnosis of schizophrenia or schizoaffective disorder. Charts of all patients who received clozapine for 24 consecutive months during a period of 48 consecutive months of hospitalization were selected for the study. For each patient, we compared the number of infections treated with an antibiotic during the 24 months pre-clozapine versus the period when they were treated with clozapine. Our study suggests that the number of antibiotic prescriptions is significantly increased in patients treated with clozapine.

Topics: Aged; Anti-Bacterial Agents; Antipsychotic Agents; Bacterial Infections; Clozapine; Female; Humans; Male; Medical Records; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies