clozapine and Heart-Arrest

Topics: Adult; Biological Availability; Clozapine; Heart Arrest; Humans; Male

Previously published case reports have noted severe adverse reactions such as cardiac arrest, respiratory arrest, and sudden death when clozapine (CLZ) and benzodiazepines (BZDs) are used concomitantly. As CLZ and BZD are both used regularly to treat psychiatric illness, it is important to have additional information concerning this potential interaction. The objective of this study was to contribute to the evolving literature by evaluating the occurrence of sudden deaths and cardiac or respiratory events leading to death in patients treated concurrently with CLZ and BZD.. A retrospective chart review was conducted at a 240-bed New York State mental health facility. Most patients in this facility have been diagnosed with refractory schizophrenia, resulting in high rates of CLZ use. Electronic and hard copy records of the 490 patients who had been treated with CLZ in this facility at any time from 2001 to 2006 were selected, and the medication records of these patients were assessed for concomitant BZD use. Information on 152 patients who were treated with CLZ and a BZD concomitantly during this time period are included in this study. Data from the facility's mortality review committee were obtained to determine sudden deaths and cardiac or respiratory events leading to death in patients treated with CLZ and BZD concomitantly. Secondary parameters also recorded during the chart review included average duration of CLZ therapy, BZD therapy, and concomitant therapy; average doses of agents used; specific BZD used; number of patients treated with a specific BZD; psychiatric diagnosis; and use of other medications that depress the central nervous system.. No deaths occurred as a result of concomitant BZD and CLZ use in the sample examined in this study, suggesting that CLZ and BZD may be safely used concomitantly in many cases. Further study is needed to determine patient characteristics or predisposing factors that might put patients at higher risk of death from this interaction. Our findings are limited by the small sample size and suboptimal frequency of side effect measurements (e.g., measurements of blood pressure and heart rate, reports of hypotensive episodes). Confounding variables that might also play a role in interactions between CLZ and BZDs, but which were not measured in this study, include other types of respiratory compromise, cognitive dysfunction, and organ dysfunction. Precautionary measures that may be used when initiating concomitant CLZ and BZD therapy include slow titration of CLZ, blood pressure monitoring, and/or nightly pulse oximeter measurements.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cross-Sectional Studies; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Heart Arrest; Humans; Male; Medical Records; Middle Aged; Respiratory Insufficiency; Retrospective Studies; Schizophrenia

To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls.. Cohort study of outpatients using administrative data.. 3 US Medicaid programmes.. Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis.. Diagnosis of cardiac arrest or ventricular arrhythmia.. Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses > or =600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038).. The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.

Topics: Adult; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Clozapine; Cohort Studies; Confidence Intervals; Death, Sudden, Cardiac; Female; Haloperidol; Heart Arrest; Humans; Male; Medicaid; Middle Aged; Risperidone; Schizophrenia; Thioridazine; United States

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Heart Arrest; Humans; Male; Psychotic Disorders; Schizophrenia, Paranoid; Syncope

To describe a patient with neutropenic fever complicated by hyperglycemia, lactic acidosis, and fatal myocardial failure associated with clozapine therapy.. A 37-year-old Ashkenazic Jewish man was admitted for agranulocytosis and fever, which developed after 11 weeks of clozapine monotherapy for drug-resistant schizophrenia. Complete blood counts and a routine serum chemical analysis had been normal before the treatment was initiated, and remained within normal limits during the first 10 weeks of the treatment. On the day of admission, the patient deteriorated rapidly and developed extreme hyperglycemia, severe lactic acidosis, recurrent cardiac arrest, cardiogenic shock, and coma. He died 36 hours later despite intensive treatment.. Clozapine intake reduced fatal aganulocytosis, associated with hyperglycemia, lactic acidosis, and heart failure. White blood cell count monitoring was insufficient to predict these adverse effects.. Clozapine should be avoided in high-risk patients (e.g., the elderly, women, Ashkenazic Jews).

Topics: Acidosis, Lactic; Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Fatal Outcome; Heart Arrest; Humans; Hyperglycemia; Jews; Leukocyte Count; Male; Risk Factors

Topics: Apnea; Benzodiazepines; Clozapine; Drug Synergism; Female; Heart Arrest; Humans; Middle Aged