DARE: the Drug-Induced Arrhythmia Risk Evaluation Study

Ventricular arrhythmias owing to psychiatric and other drugs can cause life-threatening events that are usually a result of prolongation of cardiac repolarisation, torsades de pointes and ventricular fibrillation. These events have generated public and medical concern because of their unpredictability and the lack of understanding of their epidemiological and clinical significance. Drugs such as thioridazine and droperidol have been withdrawn from the market because of this side-effect.

The Dare study is a collaboration between St George's Hospital (London) and the Drug Safety Research Unit (DSRU; Southampton), funded by the British Heart Foundation. The lead researchers are Professors A. J. Camm and S. A. Shakir. The study was launched officially on 1 July 2003 and will run for 5 years.

The study's principal aims and components are: (a) an epidemiological study to systematically document and follow-up incident cases in England, comparing them with controls - the relative risk of predisposing clinical factors will be calculated and both epidemiological cohorts will be described and the outcomes compared; (b) a genetic study to analyse blood samples from cases and controls for mutations and polymorphisms of the cardiac sodium and potassium ion channel genes implicated in the long QT and Brugada syndromes. We hypothesise that there is a significant association of genotype with drug-induced arrhythmia.

We expect that awareness of the condition and its predictability will thus be increased and result in safer prescribing and drug development.

The study will rely on recruiting patients (cases) who have had a proarrhythmic event via psychiatrists and hospital physicians in England. Inclusion criteria, diagnosed as secondary to therapeutic drug administration or drug overdose, will be at least one of the following:

1. • Documented torsades de pointes, ventricular fibrillation, or nonpolymorphic ventricular tachycardia

2. • Exacerbation of a pre-existing ventricular arrhythmia

3. • Severe drug-induced QT prolongation (QTc interval ≥500 ms)

4. • Moderate drug-induced QT prolongation (QTc interval ≥450 ms (male) or ≥ 470 ms (female)) and a clinical history of syncope or presyncope.

An information pack will be provided to all psychiatrists interested in participating in this study. The pack will include ‘consent to contact cards’ for both the patient and psychiatrist to briefly complete and return to the DSRU. This is all that will be required and we will address any local research ethics committee issues that may arise. If the patient permits contact to be made then a research nurse will arrange to visit them at home to discuss the study further and obtain consent. A questionnaire will be completed and electrocardiography performed, and a blood sample taken if the patient consents. The patient will also be asked to separately consent to access to their hospital and general practice medical notes.

We would be delighted to provide further details to interested health professionals, and are keen to visit any interested units in order to make a brief presentation. Please contact us on (023) 8040 6815, dare@dsru.org, or via http://www.dsru.org for further details or if you feel that you may have a patient meeting the inclusion criteria.