Mort subite, antipsychotiques et schizophrénie

Abstract

Sudden death is a multidimensional notion that can be defined in several ways. Epidemiologically, sudden death affects from 15 to 30% of the population and 30% of the schizophrenics. Since antipsychotic drugs appeared in 1954, the death rate of the schizophrenic population has decreased but has still remained higher than the death rate of the entire population (standardized mortality rate from 1 to 4). However, there is no proof of a decrease in the number of sudden deaths because of a lack of statistical data about the first period of time. Several factors may explain the excessively high death rate of the schizophrenics but mainly cardiovascular risk factors and an insufficient diagnosis of somatic comorbid conditions. Stress is also a well-known aetiology of sudden death: Ventricular tachycardia can occur in situations of anxiety; the Tako Tsubo syndrome is a coronarian syndrome occurring in a context of emotional stress. Death due to cardiovascular factors is probably the main aetiology of the schizophrenics’ sudden deaths, which are often associated with a prolonged QT interval (it is considered today that the QT interval is prolonged beyond 450 MS). Schizophrenia is partly the cause of these sudden deaths with regard to the stress generated by the disease. The influence of drugs on these deaths, and especially antipsychotic drugs, has also been considered. So, the use of thioridazine and sertindole was suspended after a dose-effect and sudden deaths were observed. Other antipsychotic drugs, such as haloperidol and risperidone are associated with some cases of a prolonged QT interval, with a high dosage. Another aetiology of sudden death is epilepsy: Before the rise of antipsychotic drugs, the comitial crises rate was already higher among the schizophrenics and crises occur today with or without a subjacent treatment; but antipsychotic drugs have also been incriminated in some sudden deaths. In the case of sudden deaths caused by pulmonary embolism, schizophrenia is a predisposition, especially catatonic schizophrenia. Obesity, physical restraints in case of agitated state are also the causes of a restrained mobility that can favour pulmonary embolism. As for antipsychotic drugs, and especially clozapine, they favour a gain of weight and a sedation with a high dosage, which result in a reduced mobility. As for sudden deaths caused by choking, schizophrenia contributes to these deaths through a poor mastication, a poor dentition or poor hygienic and dietetic habits. Phenothiazines can favour these deaths insofar as they favour deglutition impairment; the use of haloperidol can result in a respiratory dyskinesia that leads to asphyxia; the clozapine-benzodiazepine combination must be avoided. In the case of sudden deaths through intestinal obstruction, constipation is often poorly diagnosed for schizophrenics for whom the pain threshold is higher and because of their negative symptoms. These factors already explained the excessive death rate among the schizophrenics before the antipsychotic drugs era. But antipsychotic drugs have an analgesic effect that delays the diagnosis of constipation and an anticholinergic effect that favours constipation. The combination with a tricyclic antidepressant increases the risk. The incrimination of antipsychotic drugs in the sudden deaths of the schizophrenics remains debatable and epidemiology provides no conclusion. An autopsy is sometimes not enough to put the blame or not on antipsychotic drugs. Prevention measures about morbidity and mortality associated with antipsychotic drugs that prolonged QT, and with schizophrenia itself are proposed. The connection between sudden death and antipsychotic drugs remains poorly understood: in psychiatry, the high sudden deaths rate is due to several factors and antipsychotic drugs remain the most commonly used treatment for psychosis.