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JOANNA MONCRIEFF
Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination
The British Journal of Psychiatry 2003; 183: 161-166 [Abstract] [Full text] [PDF]
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[Read eLetter] A significant effect for clozapine despite variation between included studies
Michael D Hunter   (12 August 2003)

A significant effect for clozapine despite variation between included studies 12 August 2003
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Michael D Hunter,
Wellcome Training Fellow in Psychiatry
Academic Clinical Psychiatry, University of Sheffield

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Re: A significant effect for clozapine despite variation between included studies

m.d.hunter{at}sheffield.ac.uk Michael D Hunter

The Editor British Journal of Psychiatry 17, Belgrave Square London SW1X 8PG

11th August 2003

Dear Sir

It was with great interest that I read Moncrieff’s (2003) re- examination of published evidence for the efficacy of clozapine, versus conventional antipsychotic drugs, in treatment-resistant schizophrenia. In that paper, particular emphasis was given to heterogeneity in results between studies included in the analyses; the author warned of ‘potential danger inherent in combining results from different studies while overlooking important variations between them’.

In calculating the overall effect size for clozapine, Moncrieff employed both fixed and random effects analyses. In the former the effect size was 0.38 (95% confidence intervals 0.27-0.50) standard deviations and in the latter the effect size was 0.44 (0.15-0.73) standard deviations. Either method demonstrated a significant effect in favour of clozapine.

In contrast to fixed effects approaches, random effects analyses model both the variance within and between individuals (Bland, 2000). Random effects models can be statistically conservative (evidenced in Moncrieff’s paper by widening of the confidence intervals which, nonetheless, do not cross the point of equivalence) and allow inferences to be drawn regarding the effect of interest that are not confounded by the variance between individuals (or, in this case, individual studies).

Therefore, a parsimonious interpretation of Moncrieff’s analyses is that the current data sets demonstrate a significant effect for clozapine, in the pharmacotherapy of treatment-resistant schizophrenia, despite variation in results of individual studies.

Declaration of interest MDH has attended educational meetings sponsored by Novartis, the manufacturers of clozapine in the UK.

Bland, M. (2000) An Introduction to Medical Statistics. Oxford: Oxford University Press.

Moncrieff, J. (2003) Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination. British Journal of Psychiatry, 183, 161-166.

Michael D Hunter Wellcome Training Fellow in Psychiatry Sheffield Cognition and Neuroimaging Laboratory (SCANLab) Academic Clinical Psychiatry University of Sheffield The Longley Centre Norwood Grange Drive Sheffield S5 7JT, UK.

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