Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis
BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7273.1371 (Published 02 December 2000) Cite this as: BMJ 2000;321:1371
- John Geddes (john.geddes{at}psych.ox.ac.uk), senior clinical research fellowa,
- Nick Freemantle, reader in epidemiology and biostatisticsb,
- Paul Harrison, professora,
- Paul Bebbington, professor of social and community psychiatryc
- 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
- Accepted 3 October 2000
Abstract
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.
Footnotes
-
Funding English Department of Health as part of a larger programme of schizophrenia management guidelines to be undertaken by the National Institute of Clinical Excellence.
-
Competing interests JG, as director of the Centre for Evidence Based Mental Health, has run workshops around the United Kingdom, organised independently, but often sponsored by pharmaceutical companies. The centre has therefore indirectly received fees and expenses from several of the companies who manufacture antipsychotic drugs. NF has received funds for research, fees, and expenses from several pharmaceutical companies who manufacture antipsychotic drugs and from the Department of Health in England. PH has received support from pharmaceutical companies to attend conferences. He has also received fees for educational lectures to psychiatrists on the psychopharmcology of schizophrenia and on the work described in this paper. PB has received fees for presentations at meetings sponsored by various pharmaceutical companies who manufacture typical and atypical antipsychotics. In addition he is one of the lead investigators of the European schizophrenia cohort funded by Lundbeck.
-
Further data and members of the National Schizophrenia Guideline Development Group are available on the BMJ's website