Australian Prescriber An independent Review Logo
ISSUE 3 JUNE
Letters to the Editor

New drugs - ziprasidone

The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

 

Letter to the Editor

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.

Louise Canny
Associate Medical Director, Neuroscience
Pfizer Global Pharmaceuticals
Pfizer Australia & New Zealand

 

Editorial Executive Committee comments

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.

 

References

  1. Simpson GM, Glick ID, Weiden PJ, Romano SJ, Siu CO. Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Am J Psychiatry 2004;161:1837-47.
  2. Simpson GM, Weiden P, Pigott T, Murray S, Siu CO, Romano SJ. Six-month, blinded, multi center continuation study of ziprasidone versus olanzapine in schizophrenia. Brief report. Am J Psychiatry 2005;162:1535-8.
  3. Hirsch SR, Kissling W, Bauml J, Power A, O'Connor R. A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. J Clin Psychiatry 2002;63:516-23.
  4. Weiden PJ, Simpson GM, Potkin SG, O'Sullivan RL. Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia. J Clin Psychiatry 2003;64:580-8.
  5. Arato M, O'Connor R, Meltzer HY; ZEUS Study Group. A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study. Int Clin Psychopharmacol 2002;17:207-15.
  6. Zeldox Australian Approved Product Information. Pfizer. 2007 Jan 25.
  7. Harrigan EP, Miceli JJ, Anziano R, Watsky E, Reeves KR, Cutler NT, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol 2004;24:62-9.
  8. Breier A, Berg PH, Thakore JH, Naber D, Gattaz WF, Cavazzoni P, et al. Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia. Am J Psychiatry 2005;162:1879-87.
  9. Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck RA, et al. Effectiveness of olanzapine, quetiapine, risperidone and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry 2006;163:611-22.
  10. Kinon BJ, Lipkovich I, Edwards SB, Adams DH, Ascher-Svanum H, Siris SG. A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms. J Clin Psychopharmacol 2006;26:157-62.
  11. Heres S, Davis J, Maino K, Jetzinger E, Kissling W, Leucht S. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Am J Psychiatry 2006;163:185-94.