Abstract
Andrew Firestone, Melbourne, Australia:
Professor Sachdev has reported the suffering caused to intellectually disabled patients by abrupt termination of thioridazine treatment, as a result of regulatory overreaction in Australia in response to legitimate concerns about the risk of sudden death from thioridazine [1]. I and other colleagues in Melbourne have similarly seen well-maintained patients with chronic psychosis relapse remarkably badly upon cessation of the drug. I would like to suggest that a simple and sufficient regulatory requirement would be annual electrocardiographic (ECG) examination, similar to the recommendation made for pimozide.
My interest in this topic was stimulated by an advertisement recently distributed to all College members by a major drug company, titled ‘A consensus statement by the cardiac safety in schizophrenia group’. Curiously, the statement carried no information on our major concerns in this area – the cardiac consequences of obesity and diabetes associated with olanzapine and clozapine, and the cardiomyopathy associated with clozapine [2]. Instead, we got league tables of drugs classified for QT interval prolongation alone.
In fact, as Sachdev pointed out, that is far from a welllit area. Sudden death is more frequent in schizophrenia and polymorphic ventricular tachycardia (Torsade de Pointes) may be one cause. If so, a long QT interval may increase the risk of this. Reilly [3] showed that thioridazine and droperidol carry risk of QT prolongation beyond that of other antipsychotic drugs. However, as a recent review underlines, heavy smoking, obesity, poor diet and inactivity are important known contributors to the sudden death statistics [4].
The ‘consensus statement’ on cursory inspection might leave you with the impression that olanzapine and clozapine are drugs devoid of cardiac risk. In contrast, British College guidelines [5] warn against the combination of clozapine with a benzodiazepine.
According to the ‘consensus statement’ trifluoperazine caries risk for QT prolongation – though there appears to be no literature to support this assertion. Trifluoperazine may be cheap, but it remains a very useful drug – so let's set the record straight!
It does look, though, that as well as regular weight checks and annual fasting blood glucose, an annual ECG has to become part of our thinking.