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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 las 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 less than or equal to 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.

Original publication

DOI

10.1136/bmj.321.7273.1371

Type

Journal article

Journal

BMJ: British Medical Journal

Publication Date

2000

Volume

321

Pages

1371 - 1376

Total pages

6