Progress Report - January 2009
Current state of play
Cases have recently been documented in Sydney, Brisbane and Gosford, in addition to further cases in the Melbourne area. There are now:
- 66 confirmed cases (4 fatal)
- 79 confirmed controls
- 12 samples for DNA extraction (recruitment at only 1 site so far)
We estimate that we have ethics approvals, or applications pending, to cover about 100 cases. More ethics applications are required to complete the study.
More deaths from myocarditis
We recently became aware of a further 2 deaths from myocarditis which occurred in Melbourne and another possible case from 2008, bringing our total to 16 fatal Australian cases.
Samples from deceased cases
Ethics approvals from the Victorian Institute of Forensic Medicine and Royal Prince Alfred Hospital in Sydney cover access to samples from deceased cases with the consent of next of kin.
Article for submitted publication
The article describing the case definition and diagnostic characteristics of myocarditis has been extended to include 38 cases, with a comparison to 47 controls. The controls took clozapine for at least 6 months continuously without cardiac disease. The article was recently submitted for publication to a 4th journal, after being rejected by 3 previous journals.
Superior efficacy of clozapine
A recently published meta-analysis1 found that clozapine is superior to other antipsychotics for positive symptoms and depression and in an overall assessment. Only sertindole and amisulpride had a higher score for quality of life. These differences were not statistically significant for all comparisons. Nevertheless, this analysis is consistent with the evidence of the randomised controlled comparison between clozapine and olanzapine that clozapine is significantly protective against suicide.2
These efficacy data reinforce the importance of investigating myocarditis, in order to improve the safety of users of clozapine so it can be made more widely available. A clinically relevant outcome from this research is almost certain. Information concerning cases who have been rechallenged is also promising, although it is too early to analyse the data yet.
1. Leucht S, Corves C, Arbter D, et al. Second generation versus first generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009;373:31-41.
2. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003;60:82-91.
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