Letters to the Editor
New drugs - ziprasidone
- Aust Prescr 2007;30:59-63
- 1 June 2007
- DOI: 10.18773/austprescr.2007.036
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Editor, – I would like to update the information in your New Drug comment on ziprasidone (Aust Prescr 2007;30:50-5). Much of the data on schizophrenia comes from a Cochrane review in 2000 which states that 'well planned, conducted and reported long-term randomised trials are needed if ziprasidone is to be accepted into everyday clinical use'. However, more recent studies published since 2000 were omitted from your comment.
Of these studies, a head-to-head trial found that ziprasidone (80-160 mg/day) had comparable efficacy to olanzapine (5-15 mg/day) with differences favouring ziprasidone in observed metabolic parameters.1 These results are further supported by a 6-month double-blind extension of this study.4
Another head-to-head study of ziprasidone (80-160 mg/day) and haloperidol (5-15 mg/day) looking at relapse prevention found that both treatments were effective in reducing overall psychopathology, but ziprasidone was effective for negative symptoms and was better tolerated.4
An open-label study suggested that when outpatients who partially responded to conventional antipsychotics, risperidone or olanzapine were switched to ziprasidone their symptom-control was improved or maintained and the switch was well tolerated.4
A one-year study in patients with stable, chronic schizophrenia demonstrated that the probability of relapse was significantly lower in the ziprasidone-treated patients than those treated with placebo. In those patients who remained on treatment for at least six months, only 9% subsequently relapsed on ziprasidone compared to 42% on placebo (p=0.001).5
Regarding QTc prolongation, your comment suggests that patients being initiated on ziprasidone may need a baseline ECG and one after starting treatment. This would be ideal practice for all patients receiving any antipsychotic medication and does not apply only to ziprasidone as implied. Prescribing information for ziprasidone states that 'experience with ziprasidone has not revealed an excess risk of mortality compared to other antipsychotic drugs or placebo'.6 In patients treated with haloperidol, thioridazine, ziprasidone, quetiapine, olanzapine and risperidone, mean QTc intervals did not exceed 500 milliseconds (the accepted level for clinical significance) in any patient taking any of the antipsychotics studied, in the absence or presence of metabolic inhibition.7
It is also important to note that there is six years experience with ziprasidone overseas and that the US prescribing information contains the same precautions as for other antipsychotic medications.
Associate Medical Director, Neuroscience
Pfizer Global Pharmaceuticals
Pfizer Australia & New Zealand
It is appropriate that subsequent studies have addressed some of the issues identified by the Cochrane review. The studies cited by Dr Canny are not the only recent studies of ziprasidone. Different studies have reported advantages for other atypical antipsychotic drugs over ziprasidone.8-10
One of the problems in assessing the evidence about antipsychotics is that most trials report outcomes which favour the drug produced by the company funding the trial.11
Schizophrenia is a chronic condition, but the head-to-head comparison with olanzapine only lasted six weeks. Although the trial was short, 49 of the 133 patients taking olanzapine and 66 of the 136 taking ziprasidone discontinued treatment.1 Only 126 patients entered the six-month continuation study and by the end of the trial there were only 17 patients left taking ziprasidone and 21 patients taking olanzapine.2
Two of the trials discussed by Dr Canny3 ,5 appear to have been included in the Cochrane review so their publication does not change our conclusions.
Another study quoted by Dr Canny pools data from three trials. This open-label switching study does not provide strong evidence for the efficacy and tolerability of ziprasidone.4
Ziprasidone seems to cause greater mean increases in QTc intervals compared to olanzapine, haloperidol, quetiapine and risperidone.1-3 , 7 Unlike other atypical antipsychotic drugs, the Australian prescribing information for ziprasidone includes a contraindication for patients who have a condition that potentially prolongs the QTcinterval.6 We believe this is important information for prescribers and may help in treating patients with schizophrenia.