Arrhythmias and sudden death in patients taking antipsychotic drugs

摘要

The first report that patients with schizophrenia might be at special risk of arrhythmia and sudden death appeared in the early 1960s, when thioridazine was found to prolong the QT interval, an electrocardiographic abnormality that could lead to torsades de pointes and sudden death. This same problem arose with sertindole―lengthening of the QTc interval and an apparent excess of sudden deaths in clinical trials―and led the US Food and Drug Administration to refuse it a licence. Nevertheless, whether cardiac deaths are related to the illness itself or to the drugs used to treat it has remained unclear. Data from a very large American cohort of almost 100 000 outpatients with schizophrenia who were treated with antipsychotics were published recently and begin to suggest an answer: the drugs play a major part, although a risk factor conferred by the disease or associated with it may contribute (for example, smoking). The study originated from unpublished preclinical work comparing ziprasidone, a new atypical anti-psychotic drug that Pfizer had developed, with established antipsychotics. Ziprasidone caused notable QTc prolongation, and the FDA had concerns about licensing it mainly because of this abnormality.