ArticlesSecond-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis
Introduction
The high costs of second-generation (atypical) antipsychotic drugs, with $7·5 billion sales in the USA in 2003,1 has led to a continuing debate about their benefits compared with first-generation compounds. Limitations of previous reviews2, 3 were that they analysed only one global efficacy outcome, even though the main advantage of second-generation antipsychotic drugs is claimed to be their broad efficacy spectrum. In particular, these drugs are thought to improve negative symptoms, depression, and quality of life more than do conventional antipsychotic drugs. Improved efficacy for these problems is thought to be a major characteristic of the atypicality of second-generation antipsychotic drugs, in addition to a reduction in extrapyramidal side-effects. In previous meta-analyses (apart from Cochrane reviews), side-effects were not assessed thoroughly, even though they are important criteria in drug choice. Furthermore, the number of randomised controlled trials in which antipsychotic drugs were assessed is continually increasing, making new meta-analyses necessary. We present a meta-analysis of randomised controlled trials to compare the effects of second-generation antipsychotic drugs with first-generation antipsychotic drugs on several outcomes in patients with schizophrenia.
Section snippets
Search
We searched (without language restrictions) the register of the Cochrane Schizophrenia Group,4 US Food and Drugs Administration website, and previous reviews2, 3, 4 for randomised controlled trials in which oral formulations of second-generation antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, and zotepine) were compared with first-generation antipsychotic drugs for the treatment of schizophrenia or related disorders
Search
Our search yielded 4166 citations. Of 411 inspected, we excluded 107 studies for reasons of inadequate randomisation (n=50), no appropriate intervention or control group (n=29), inappropriate participants (n=2), no usable data (n=24), presentation of a subgroup only (n=1), and very short duration (ie, 5 days; n=1). Another 65 open or single-blind studies were excluded after the absence of double blind was detected as a bias.
We included a total of 239 publications of 150 double-blind studies
Discussion
Four second-generation antipsychotic drugs—amisulpride, clozapine, olanzapine, and risperidone—were more efficacious than first-generation drugs in the main domains (overall change in symptoms, and positive and negative symptoms). The other five second-generation antipsychotic drugs were only as efficacious as first-generation antipsychotic drugs, even in terms of negative symptoms. Second-generation antipsychotic drugs caused fewer extrapyramidal side-effects than did haloperidol, even when
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