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The usefulness and use of second-generation - page 33 / 81





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Other developments relevant to the use of second-generation antipsychotic medications

Recent meta-analyses

In an effort to gain a coherent and comprehensive view of the effectiveness of SGAMs, statistical reviews using meta-analytic methods have been carried out. Meta-analyses of a series of studies can be useful in aggregating the results of individual studies and producing a summary statistic bearing on questions of comparative effectiveness of treatments or classes of treatments. In the case of the SGAMs, the comparisons have been between one SGAM and comparators (a placebo and the antipsychotic drug), and between SGAMs and FGAMs. The advantage of meta-analyses is that by aggregating studies they can enhance statistical power. Thus, while some individual studies may be large enough (in terms of numbers of subjects per treatment arm) to reach statistically significant differences, the combining of studies enables small or moderate effects to be detected. In addition, meta-analyses provide a measure of the consistency of treatment effects and their magnitude. The major limitation of meta-analyses is that they are wholly dependent on the quality of the constituent studies and the data therein. They also can be subject to over-interpretation or misinterpretation.

The Register of Trials of the Cochrane Schizophrenia Group maintains a database of trials on antipsychotic drugs, and periodically performs meta-analyses of their results (http://www.cochranelibrary.com). They have performed reviews of all of the SGAMs in comparison with placebos, FGAMs and other SGAMs. Overall, these reviews have found that the SGAMs are clearly superior to placebos and mostly equivalent to the FGAMs, with the exception of clozapine - which is clearly superior to FGAMs, but there is insufficient evidence to evaluate the comparative effectiveness of the current SGAMs. A brief review of the recent meta-analyses of SGAMs follows.

Leucht et al. [235]  reviewed studies that evaluated the efficacy and tolerability of olanzapine, risperidone, quetiapine and sertindole. The results of their meta-analysis indicated that the SGAMs were superior to placebos; quetiapine and sertindole were as effective as haloperidol, and olanzapine and risperidone were slightly more effective than haloperidol in the treatment of global schizophrenic symptoms. With respect to negative symptoms, olanzapine and risperidone were slightly superior to haloperidol. All the SGAMs were associated with less frequent use of antiparkinsonian medication than haloperidol.

Geddes et al. [140] reported, for the National Schizophrenia Guideline Development Group, the results of a meta-analysis comparing all SGAMs and FGAMs on overall symptom scores and rates of drop-out, which they considered a proxy for tolerability, particularly of EPSs. They found substantial heterogeneity in the results, which was partially accounted for by the dose of the SGAM comparator used: when the dose used was up to 12 mg/day in haloperidol equivalents, FGAMs and SGAMs were equivalent on symptom reduction and tolerability. Based on this, they concluded that the FGAMs

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