clozapine and Respiratory-Tract-Infections

Topics: Anti-Bacterial Agents; Antipsychotic Agents; Clozapine; Comorbidity; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Drug Administration Schedule; Drug Interactions; Humans; Mental Disorders; Respiratory Tract Infections

Locked pediatric inpatient psychiatric units are vulnerable to the emergence and spread of infections, and nosocomial infection, especially respiratory tract infection is potentially a major problem. This study aimed to explore the risk factors for lower respiratory tract infection (LRI), in particular, pneumonia.. We conducted a retrospective study comprising 4643 patients with schizophrenia (SZ) and 1826 patients with major depressive disorder (MDD), and the chi-square test was performed to analyze the categorical variables.. The risk ratio for LRI, including pneumonia, in intensive care unit (ICU) was higher than in the general ward, and electroconvulsive therapy (ECT) increased the patients' susceptibility to LRI and pneumonia. Our data have revealed that patients treated with restraint or clozapine showed a higher prevalence of LRI and pneumonia, and the results indicated that the increased risk of LRI, not pneumonia, was dose-dependently observed in patients with clozapine treatment.. Our study shows that ICU and ECT treatment were risk factors for LRI and pneumonia in patients with SZ or MDD, and patients with SZ has a prevalence of hospital-acquired infection because of restraint and clozapine treatments.

Topics: Child; Clozapine; Cross Infection; Depressive Disorder, Major; Hospitals, Psychiatric; Humans; Respiratory Tract Infections; Retrospective Studies; Risk Factors

We aimed to investigate the effects of infection on serum concentrations of different antipsychotics in inpatients with respiratory tract infections treated with psychiatric drugs, including risperidone, clozapine, quetiapine, and aripiprazole. All patients underwent therapeutic drug monitoring (TDM) and routine blood tests during infection and noninfection periods. The Wilcoxon signed-rank test was used to analyze intra-individual differences in dose-corrected serum concentrations (C/D) levels in infection and noninfection periods. To study the effects of infection intensity on drug concentrations, white blood cells (WBCs) parameters and C/D levels were analyzed by Spearman's correlation analysis using all samples. The median C/D levels of risperidone (risperidone + 9-OH, n = 36) and clozapine (n = 42) were significantly higher (P < 0.001), whereas the median C/D levels of quetiapine (n = 21) and aripiprazole (n = 13) were slightly significantly higher (P < 0.01) in infection than in noninfection period. A significant positive association between C/D levels and WBC parameters was observed for risperidone, clozapine, and quetiapine. These results indicated reduced clearance of all drugs evaluated, especially clozapine and risperidone, due to infection. Therefore, during infection in patients receiving risperidone, clozapine, quetiapine, or aripiprazole, TDM should be performed to minimize the possible adverse effects associated with elevated drug concentrations.

Topics: Antipsychotic Agents; Aripiprazole; Clozapine; Humans; Quetiapine Fumarate; Respiratory Tract Infections; Risperidone

Objective Serious infections or inflammations have been associated with serum clozapine concentration increases and sometimes with clozapine toxicity. Method These two cases describe Chinese patients (Case 1: a 57-year-old female nonsmoker with severe dermatitis and Case 2: a 47-year-old male nonsmoker with influenza and secondary infection). Results In both cases, the Drug Interaction Probability Scale established the presence of a probable drug-drug interaction. In both cases, the clozapine and the total clozapine concentration-to-dose ratios followed a temporal pattern (normal-high-normal), consistent with an inhibition of clozapine metabolism during peak inflammation. In the first case, the total clozapine concentration-to-dose ratio (8 with no/low inflammation: median of 3.10 and 2 at peak inflammation: median of 3.90) provided a significant difference (P = 0.044). In the second patient, because of the smaller sample size and reduced statistical power (4 with no infection: a median of 1.59 and 2 at peak infection: 3.46), the increase did not reach significance (P = 0.13). In the first case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 1.45 from 2.00 to a peak of 2.89. To compensate for the inhibition of clozapine metabolism, the dose correction factor was 0.69 (1/1.45) or a decrease in dose of approximately one-third. In the second case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 2.56 from 1.15 to a peak of 2.94. Conclusion This provided a dose correction factor of 0.40 (1/2.56) or approximately half the dose, similar to published cases in Caucasians with serious respiratory infections.

Topics: Antipsychotic Agents; Asian People; Clozapine; Cytokines; Dermatitis; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Inflammation; Influenza, Human; Male; Middle Aged; Psychotic Disorders; Respiratory Tract Infections

The following report presents a case in which significant clozapine toxicity was demonstrated in a patient on established therapy, in the absence of identifiable risk factors. Through this case report, the authors aim to highlight the potential for clozapine toxicity to occur unexpectedly in times of acute medical illness, and the need to remain vigilant in such situations.. Case report and review of the relevant literature.. We describe a case of a 62 year old man whom developed life-threatening clozapine toxicity in the context of a severe lower respiratory infection. Following investigation to exclude the usual causes of toxicity, it was surmised that impaired CYP1A2 function, secondary to the acute inflammatory process, had led to a toxic level of the drug.. Given the possibility that serum clozapine levels may significantly rise in acute illness, the team recommends measurement of clozapine levels in these situations, in combination with the usual full blood count investigation. Such a practice should be considered in the local monitoring protocol, to avoid incidence of potentially toxic outcomes.

Topics: Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP1A2; Humans; Male; Respiratory Tract Infections

We report the case of a patient with schizophrenia, who experienced agranulocytosis during clozapine treatment, followed by bronchopulmonal infection and Guillain-Barré syndrome. The case was recorded within the German surveillance project "drug safety in psychiatry" (AMSP).

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Female; Guillain-Barre Syndrome; Humans; Middle Aged; Psychomotor Agitation; Respiratory Tract Infections; Schizophrenia; Sepsis

Clozapine is mainly metabolized by the cytochrome P450 1A2 (CYP1A2), which may be inhibited by serious respiratory infections. This case report supports that a serious respiratory infection may increase clozapine levels and contribute to side effects. Plasma clozapine and norclozapine levels were monitored 17 times during 1 year. The concentration-to-dose ratio (C/D), an index of metabolic activity, was obtained by dividing the sum of plasma clozapine and norclozapine concentration (total clozapine concentration) by clozapine dose. The coefficient of variation (CV) of the total clozapine concentrations was calculated at different doses to provide a measure of the noise associated with determining clozapine concentrations in clinical practice. During a respiratory infection, the patient was taking 600 mg/day of clozapine. Clozapine levels were 1245 ng/ml (norclozapine 472 ng/ml), reflecting a decrease in clozapine metabolism by approximately a factor of 2. The high clozapine levels were associated with side effects (myoclonus and increased sedation). The C/D during the infection was 2.9, while the rest of C/Ds ranged between 1.0 and 1.6. CVs before and after the infection, at different doses, were always lower than 20%. When the level during the infection was included to calculate the CV on 600 mg/day, the CV increased to 54%. The theophylline literature, a prior case report and this case all suggest that if a clozapine patient develops a severe respiratory infection with fever, the psychiatrist must pay particular attention to any signs suggestive of major clozapine toxicity associated to a decrease in clozapine metabolism. If any of these signs appear, the psychiatrist may need to consider cutting the clozapine dose in half until the patient has recovered from the infection.

Topics: Adult; Clozapine; Cytochrome P-450 CYP1A2; Humans; Male; Respiratory Tract Infections