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The Royal College of Psychiatrists Improving the lives of people with mental illness

OP51. The Management of Schizophrenia Part 1: Pharmacological Treatments


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Published: Sep 2001

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This document describes the systematic review undertaken to inform the guideline development work of the Royal College of Psychiatrists Research Unit and British Psychological Society Centre for Outcomes Research and Effectiveness on the pharmacological management of schizophrenia. It describes explicitly the evidence from which recommendations can be made and is therefore intended to form the source document from which clinical practice guidelines can subsequently be drawn for use in daily practice.
 
This work was undertaken as of a programme of guideline development work funded by the Department of Health. The work also includes a review of the evidence of the role of psychosocial interventions in the management of schizophrenia (in progress).
The recommendations contained in the report are the views of the technical development group and do not necessarily represent the views of the Royal College of Psychiatrists or the British Psychological Society.
 
There is considerable variability between the results of trials of atypical antipsychotic drugs, even when the same atypical and comparator drugs are used, making simple combined estimates from trials of limited value. Most trials are short term (6-8 weeks) and provide limited evidence on how best to treat patients in the longer term. There is no evidence of specific effects for atypical drugs upon negative and depressive symptoms. Effects, when they occur, seem equally to involve all classes of symptoms.
 
Observed differences in the results of trials may be explained by variation in the dose of the comparator conventional antipsychotic used. Adjusting for dose, the apparent benefits of the atypical antipsychotics on overall symptom scores are no longer present when compared with currently recommended doses of haloperidol or chlorpromazine, indicating that the trials use conventional drugs in doses that are inappropriately high. Although drop out is reduced in trials comparing atypical antipsychotics with conventional antipsychotics used at higher doses, at lower doses conventional antipsychotics appear similarly tolerated to the newer drugs. Atypical antipsychotics are associated with a reduced risk of extra pyramidal side-effects even in trials where lower doses of haloperidol are used. An analysis based on the extension phases of three randomised trials comparing olanzapine and haloperidol suggests a significant reduction in tardive dyskinesia in chronic patients at high risk. However, there are no direct data on the relative incidence of tardive dyskinesia in lower dose trials of conventional antipsychotic drugs. There have been reports of suspected neuroleptic malignant syndrome in trials of at least one atypical drug currently licensed. Information on the relative incidence of treatment emergent side-effects is surprisingly limited for atypical drugs.
 
Direct randomised comparisons between atypical drugs are inadequate to provide reliable evidence on their relative effectiveness. However, there is limited evidence of improved tolerability with olanzapine compared with risperidone.
 
In long term trials of 1 or 2 year duration, psychiatric symptom scores for the newer drugs demonstrate only modest gains and in one case no improvement. Two large US studies describe net costs of care and present imprecise findings. The net cost of prescribing atypical antipsychotic drugs in the UK setting remains uncertain and it cannot be presumed that savings from reduced hospitalisation or use of other services will offset their higher acquisition cost. There are only limited data to inform decision making about the treatment of first episode schizophrenia. In this patient group, trial data are required to explore the influence of the choice and dose of drug given, presenting a profile of costs and consequences relevant to the UK health care setting.
 
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