BMJ 2000;321:1371-1376 ( 2 December )

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Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis

Editorial by Kapur and Remington

John Geddes, senior clinical research fellow, a Nick Freemantle, reader in epidemiology and biostatistics, b Paul Harrison, professor, a Paul Bebbington, professor of social and community psychiatry, c for the National Schizophrenia Guideline Development Group.

a Department of Psychiatry University of Oxford, Warneford Hospital, Oxford OX3 7JX, b Medicines Evaluation Group, Centre for Health Economics, University of York YO10 5DD, c Department of Psychiatry and Behavioural Sciences, Royal Free and University College Medical School, London W1N 8AA

Correspondence to: J Geddes john.geddes{at}psych.ox.ac.uk

Objective: To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia.
Design: Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines.
Subjects: 12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or chlorpromazine) or alternative atypical antipsychotics.
Main outcome measures: Overall symptom scores. Rate of drop out (as a proxy for tolerability) and of side effects, notably extrapyramidal side effects.
Results: For both symptom reduction and drop out, there was substantial heterogeneity between the results of trials, including those evaluating the same atypical antipsychotic and comparator drugs. Meta-regression suggested that dose of conventional antipsychotic explained the heterogeneity. When the dose was =<12 mg/day of haloperidol (or equivalent), atypical antipsychotics had no benefits in terms of efficacy or overall tolerability, but they still caused fewer extrapyramidal side effects.
Conclusions: There is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics. Conventional antipsychotics should usually be used in the initial treatment of an episode of schizophrenia unless the patient has previously not responded to these drugs or has unacceptable extrapyramidal side effects.


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