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.