Abstract
David Ames, John Camm, Peter Cook, Peter Falkai, Charles Gury, Rod Hurley, Gordon Johnson, Robert Piepho and Victor Vieweg; members of the Cardiac Safety in Schizophrenia Group:
Andrew Firestone's recent letter to the journal [1] raises a number of points on which we, the members of the Cardiac Safety in Schizophrenia Group (CSISG), would like to comment.
The CSISG was formed to address issues associated with cardiac safety in schizophrenia, raise awareness of cardiac issues related to drugs used to treat schizophrenia (with a specific focus on the currently topical issue of clinically significant QTc prolongation), help psychiatrists minimize potential cardiac risks associated with treating schizophrenia and to produce educational materials on cardiac safety in schizophrenia. Cardiac Safety in Schizophrenia Group is supported by an unrestricted educational grant from the Eli Lilly Company and is administered through the company Cohn & Wolfe Ltd. The nine members of CSISG listed above represent an international cross section of psychiatrists, cardiologists, pharmacists and pharmacologists working with patients who have schizophrenia. We have prepared and published a consensus statement ‘Minimizing the risks associated with significant QTc prolongation in people with schizophrenia’ [2].
The publication by Eli Lilly Australia of a single table extracted from the first edition of the Consensus Statement [2] as an advertisement was unfortunate, occurred without prior knowledge of the members of CSISG, and did not meet with our approval. In our opinion the Consensus Statement [2] should be read as a whole and should not be used in advertising. Shortly after the advertisement appeared Cohn & Wolfe communicated with Eli Lilly and were assured that the Consensus Statement [2] would not be used again in a promotional or advertising context for Eli Lilly products.
We agree with Dr Firestone that precipitate regulatory action (as occurred when the Australian Drug Evaluation Committee restricted the availability of thioridazine) may not always be in the best interests of all patients. This is one of the reasons why we agreed to produce a Consensus Statement [2] to try and give guidance in this area for practitioners around the world, because the regulatory response to the emerging knowledge that certain antipsychotic drugs can produce QTc prolongation has varied very widely in different jurisdictions. Unfortunately, a simple annual electrocardiogram (ECG) examination as suggested by Dr Firestone, may miss state dependent alterations in ECG traces and could lull prescribers into a false sense of security with respect to drugs that have the potential to prolong QTc [2].
There is now an emerging body of evidence to indicate that the potential dangers of thioridazine [2–4] may indeed be excessive compared to those posed by other antipsychotics. We agree with Dr Firestone that the positioning of trifluoperazine within our table has the potential to cause controversy, but we note that the report of the Royal College of Psychiatrists Psychopharmacology Working Group on the association between antipsychotic drugs and sudden death (1997) [5] also listed trifluoperazine on page 16 of the report as a drug known to prolong the QT interval of the ECG. The association between trifluoperazine use and ECG abnormality has been documented since 1964 [6].
The Consensus Statement [2] makes reference to other issues of cardiac safety in schizophrenia including smoking, weight gain, diet and hyperglycaemia, all of which warrant guidelines in their own right.