[Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia].
Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval.
Gury
C
C
Service de Pharmacie Clinique, CH Sainte-Anne, Paris.
Canceil
O
O
Iaria
P
P
D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy*; D016171:Torsades de Pointes / Q000139:chemically induced*
D014150:Antipsychotic Agents
Antipsychotiques et sécurité cardio-vasculaire: données actuelles sur les allongements de l'intervalle QT et le risque d'arythmies ventriculaires.