ArticlesNew generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis
Section snippets
Summary
Background The clearest advantage of new generation, atypical antipsychotics is a reduced risk of extrapyramidal side-effects (EPS), compared with conventional compounds. These findings might have been biased by the use of the high-potency antipsychotic haloperidol as a comparator in most of the trials. We aimed to establish whether the new drugs induce fewer EPS than low-potency conventional antipsychotics.
Methods We did a meta-analysis of all randomised controlled trials in which new
Identification of trials
Randomised controlled trials were identified that compared new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, remoxipride, risperidone, sertindole, ziprasidone, and zotepine) with low-potency conventional drugs (chlorpromazine, chlorprothixene, levomepromazine, melperone, mesoridazine, methotrimeprazine, perazine, pipamperone, promethazine, prothipendyl, thioridazine).
Chlorpromazine is a standard low-potency conventional antipsychotic. These drugs are labelled
Statistical analysis
We combined data from all eligible studies in a meta-analysis using risk differences, and used 95% CIs as a measure of effect size. The risk difference—ie, the risk of an unfavourable outcome in experimental treatment-allocated participants, minus the corresponding risk in controls—was used because we expected low frequencies of EPS in both groups. The risk difference gives more meaningful results than relative risks and odds ratios in such situations. To combine the results of the individual
Results
A search of the Cochrane schizophrenia group yielded 109 citations of which 60 were excluded. Four were not relevant, 29 did not use a low-potency antipsychotic comparator, 14 were not randomised (case series or controlled clinical trials), nine were reviews with no usable data,three investigated healthy volunteers,and one study was still in the planning phase. Thus,49 references for 27 studies were identified (only the principal reference of each study is indicated).We identified 3 studies
Discussion
The results of our review indicate that there is a reasonable amount of evidence to suggest that clozapine produces fewer EPS than conventional drugs. Less robust evidence points to a similar result for olanzapine. For amisulpride, quetiapine, and risperidone only one, inconclusive, trial was identified. Further evidence shows that zotepine and remoxipride do not lead to fewer EPS than chlorpromazine or similar drugs. The data indicate a dose effect because, for doses less than 600 mg/day
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