Electrocardiogram and cardiovascular changes in thioridazine and chlorpromazine poisoning

To examine the effects of anti-psychotic medications on cardiovascular parameters in overdose. Specifically, to examine dose-response relationships for thioridazine and chlorpromazine.

A retrospective study of case records of patients presenting to the Edinburgh poisons treatment unit over 3 years (2000-2002). Information--including that on stated dose ingested, ECG parameters, and pulse and blood pressure--was extracted from case notes.

A total of 224 chlorpromazine, 96 thioridazine and 99 patients ingesting other anti-psychotics were evaluated. Full data on all aspects, both dose and cardiovascular change, was available in 96 chlorpromazine, 36 thioridazine and 27 of the other anti-psychotic cases. For thioridazine, there was a significant dose-response relationship for increasing heart rate and increasing QTc but not other cardiovascular changes. For chlorpromazine, there was no dose-response relationship for ECG changes, but there was a significant dose-response relationship for increasing heart rate and reduction in mean blood pressure.

We have confirmed a relationship between increasing dose of thioridazine and prolongation of QTc in overdose patients. No such change was observed with chlorpromazine. Both of these agents are reported to cause QT prolongation, but this study suggests that the nature of these effects is different for each agent. Poisoned patients may offer ways of exploring in more detail, and at a larger dose range, the effects of potentially cardiotoxic drugs in humans.