The Pharmaceutical Journal
Vol 269 No 7228 p860
14 December 2002

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College of Mental Health Pharmacists/Industrial Pharmacists Group summary

Cardiovascular mortality is higher in those who are severely mentally ill

The cardiovascular mortality of the severely mentally ill is higher than in the normal population, explained Joe Reilly, consultant adult psychiatrist, Tees and North East Yorkshire NHS Trust.

The question is whether this is the result of schizophrenia and its variety of associations which increase cardiovascular risk, or the result of drug therapy, he said. As with other drug classes, all antipsychotics block potassium channels in the myocardium and some patients on antipsychotics, particularly those on higher doses, have QT abnormalities on ECG which are predictors of ventricular arrhythmias. Dr Reilly said that it is probably acceptable for drugs to cause QT prolongation if they have a short half-life, their metabolism is not complex, their elimination is predictable and there are no extensive drug interactions. However, if there is a dose-response relationship and one is looking at differential effects, this would be more supportive of it being a drug effect, he said.

A QT prolongation dose-response relationship has been found for thioridazine and droperidol but most atypicals have not yet been examined sufficiently to be totally excluded, particularly when given with other antipsychotics. The Food and Drug Administration committed Pfizer to do a specific study and there was an indication that ziprazidone and thioridazine caused clinically significant prolongations in more patients than haloperidol or other atypicals did.

Dr Reilly said that he is not a fan of blanket screening all patients. Finding the patients at high risk is of major importance. The elderly, patients with existing cardiac disease, hypokalaemia or malnutrition (including anorexia), or those with a family history of prolonged QTc or early sudden death are all "at risk" and should be considered for screening. However, a small QT effect does not necessarily mean the drug is safe and the same reassurance can not be gained through ECG screening as it can, for example, by undertaking blood monitoring. QTc prolongation should not be of major concern every time an antipsychotic is prescribed, commented Dr Reilly. In any case, a perspective must be maintained on this occurrence, which is rare compared with other adverse effects of antipsychotic therapy. In response to a question, Dr Reilly said that he was surprised and disappointed when droperidol was withdrawn from the market.