A dose-related increase in risk of lengthened QT-interval has been reported in patients taking tricyclic antidepressants, droperidol (Droleptan) or thioridazine (Melleril) at therapeutic doses.
Dr Joseph Reilly (academic department of psychiatry, University of Newcastle-upon-Tyne) and colleagues measured the frequency of QT lengthening in 495 psychiatric patients receiving psychotropic medication.
Overall, abnormal values were found in 40 (8 per cent) of the psychiatric patients. Lengthened QT intervals were found in 23 (8 per cent) of 286 patients who were taking antipsychotic drugs alone, five (11 per cent) of 44 patients taking tricyclic antidepressants alone and eight (15 per cent) of 53 who were taking combinations of antipsychotics and tricyclic antidepressants.
The authors note that the variables that remained significant predictors of QT lengthening were age (over 65 years) or use of tricyclic antidepressants, droperidol or thioridazine. Increasing antipsychotic dose was associated with increased chance of QT lengthening, they say. They did not find a significant association with any specific psychiatric disorder, alcohol misuse, cardiovascular disease or any other drug therapy.
"Our results suggest that therapeutic doses of tricyclics lengthen the QT interval independently of the presence of cardiovascular disease," the authors say. They go on to suggest that electrocardiographic monitoring is needed in patients taking these drugs at therapeutic doses, particularly if other risk factors are present.
Dr Robert Donnelly (medical director, Janssen-Cilag, UK) commented on April 4 that the summary of product characteristics (SPC) for droperidol states that the drug should be used with caution in patients with cardiac arrhythmias and other predisposing factors. Any QT interval prolongation was more marked in overdose but could occur at therapeutic doses, he added. The SPC for thioridazine (Melleril) carries a similar warning.
We omitted to state that the reference was to a paper in the Lancet (2000;355:1048).