clozapine and Death--Sudden

An increasing number of reports suggest a link between venous thromboembolism (VTE) and the use of antipsychotics. To better understand this association the available body of evidence has been critically scrutinised. Relevant articles were identified in the databases Scopus and PubMed. Several observational studies using different methodologies show an increased risk of VTE in psychiatric patients. This elevated risk seems to be related to the use of antipsychotic medication and in particular to the use of clozapine and low-potency first-generation drugs. Many studies investigating the association have, however, methodological limitations. The biological mechanisms involved in the pathogenesis of this possible adverse reaction are largely unknown but several hypotheses have been suggested such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinemia and hyperprolactinemia. The association may also be related to underlying risk factors present in psychotic patients. Physicians need to be aware of this possible adverse drug reaction. Although supporting evidence has not been published they should consider discontinuing or switching the antipsychotic treatment in patients experiencing VTE. In addition, although data is lacking, the threshold for considering prophylactic antithrombotic treatment should be low when risk situations for VTE arise, such as immobilisation, surgery and so on.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Case-Control Studies; Catatonia; Clozapine; Death, Sudden; Dehydration; Female; Humans; Male; Middle Aged; Models, Biological; Platelet Aggregation; Pulmonary Embolism; Restraint, Physical; Retrospective Studies; Risk; Risk Factors; Thrombophilia; Venous Thromboembolism; Young Adult

Serious adverse events and even sudden death have been reported during administration of the combination of clozapine and benzodiazepines. However, this combination does not necessarily result in increased frequency of serious adverse events. Thus it is not regarded as an absolute contraindication and might be useful in distinct clinical situations, e.g., during the occurrence of a malignant neuroleptic syndrome, "catatonic dilemma," or severe agitation during clozapine treatment. In the following report, certain suggestions on how to deal with this combination therapy are provided which may provide a basis for discussion that ultimately may lead to the formulation of guidelines for this combination therapy. Such guidelines may help psychiatrists in dealing with this combination in clinical situations. Moreover, the formulation of such guidelines would help with forensic issues in case of serious adverse events occurring during this combination therapy.

Topics: Adverse Drug Reaction Reporting Systems; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Clozapine; Death, Sudden; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Neuroleptic Malignant Syndrome; Practice Guidelines as Topic; Risk Factors

Clozapine-associated induction of venous thromboembolism has potentially catastrophic consequences. We report a case of sudden death caused by bilateral main pulmonary trunk thrombosis in a 31-year-old man receiving clozapine therapy. The patient presented with general weakness and exertional dyspnea. Bilateral main pulmonary trunk thrombosis was clearly demonstrated by helical chest computed tomography.

Topics: Adult; Antipsychotic Agents; Clozapine; Death, Sudden; Emergency Medicine; Fatal Outcome; Humans; Male; Pulmonary Embolism; Schizophrenia; Treatment Refusal

The risk of sudden death during clozapine treatment is controversial. The authors present a review of sudden deaths that occurred at Sha'ar Menashe Mental Health Center between January 1991 and August 1997. The number of cases of deceased inpatients was retrieved from the hospital's computerized database and divided into three groups: sudden death, suicide, and disease-related death. Copies of mandatory reports of sudden death filed with the Ministry of Health were obtained, and the corresponding patient records were reviewed. The rates of sudden death, suicide, and disease-related deaths were calculated for clozapine-treated patients (CTPs) during and after treatment and for patients treated with other psychiatric agents (non-CTPs). Among 561 CTPs, there were 4 sudden deaths during treatment, 2 sudden deaths after treatment, 2 suicides during treatment, and 2 disease-related deaths during treatment. Among 4918 non-CTPs, there were 14 sudden deaths, 5 suicides, and 86 disease-related deaths, all of which occurred during treatment with other psychiatric agents. CTPs who experienced sudden death were 10.37 years younger and healthier than non-CTPs who experienced sudden death. The sudden death rate was 3.8 times higher for CTPs than for non-CTPs, whereas the rate of disease-related death was 5 times higher for non-CTPs than for CTPs. Contrary to expectations, the rate of suicide among patients currently receiving clozapine in this sample was 3.6 times higher than among non-CTPs. Because CTPs who experienced sudden death were also younger and healthier, it seems that treatment with clozapine may present a greater risk for sudden death than treatment with other psychiatric medications. The limited number of sudden death cases and deaths from other causes should be noted so that these findings are considered with caution.

Topics: Aged; Antipsychotic Agents; Clozapine; Death, Sudden; Humans; Israel; Male; Middle Aged; Suicide

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

Topics: Adult; Clozapine; Death, Sudden; Drug Interactions; Drug Therapy, Combination; Humans; Injections, Intravenous; Lorazepam; Male; Respiratory Insufficiency; Schizophrenia, Paranoid; Sleep Wake Disorders

Two fatal cases are represented in which the intake of the tricyclic neuroleptic drug with the active ingredient clozapine was involved. The chemical toxiological results are showed and in connection with the results of the autopsies and the case history discussed.

Topics: Adult; Cause of Death; Clozapine; Death, Sudden; Dibenzazepines; Humans; Male; Schizophrenia; Suicide; Tissue Distribution

Topics: Acute Disease; Adult; Clozapine; Death, Sudden; Dibenzazepines; Humans; Male; Myocarditis