Antipsychotic linked to sudden unexplained death in psychiatric patients

Abstract

N research supports earlier evidence that the antipsychotic drug thioridazine may increase the risk of sudden death by delaying ventricular repolarisation and causing torsades de pointes, British researchers report. In 2000, UK and US regulatory agencies issued warnings about the drug, which had been shown to prolong the QTc interval in a dose-related manner. Simon H L Thomas (University of Newcastle upon Tyne, Newcastle, UK) and colleagues investigated sudden, unexplained deaths that took place among in-patients at five psychiatric hospitals in northeast England. There were 1350 deaths in 12 years. Of those, 77 deaths met the criteria for “probable” and 27 for “confirmed” sudden, unexplained death. 69 cases were each matched to two controls, one of which had the same primary diagnosis as the case patient. Sudden, unexplained deaths were associated with hypertension, ischaemic heart disease, and thioridazine treatment (adjusted odds ratio for thioridazine 5·3, p=0·004; Br J Psych 2002; 180: 515–22). The primary cause of thioridazine-related deaths seemed to be torsades de pointes, although a dose-response effect with high-dose or low-dose thioridazine was not observed. Other antipsychotics used by the patients studied were not significantly associated with sudden unexplained death, the researchers found. “Although the effect is rare, thioridazine seems to be more potent than the majority of other drugs that affect cardiac repolarisation, and this may be linked to sudden cardiac death”, Thomas told The Lancet. “Unless there’s a good reason for a patient to continue on thioridazine, it’s appropriate that other antipsychotic drugs be considered”, he advises. However, he points out that a number of other antipsychotic drugs, such as pimozide, sertindol, and droperidol, may also have this effect. In a related editorial, Wayne A Ray (Vanderbilt University, Nashville, TN, USA) notes that the study did not have sufficient power to demonstrate that thioridazine was associated with greater risk than the other specific drugs. But he suggests that it would be “prudent to assume that all available antipsychotics have the potential to increase the risk of serious ventricular arrhythmias and thus sudden cardiac death”.