This report replaces Consensus statement on the use of
high-dose antipsychotic medication (CR26 from 1993) and
The association between antipsychotic drugs and sudden
death (CR57 from 1997).
This revised statement reflects the consensus opinion of the
members of the Working Group. It addresses the use of high-dose
antipsychotic medication only in adult mental health services, and
not other psychiatric services such as child and adolescent,
elderly, and learning difficulties. Recommendations are made in
respect of clinical practice for those involved professionally, as
part of a multidisciplinary team or individually, with people
receiving antipsychotic medications. Guidance on implementing these
recommendations is provided. The issue of compatibility between the
proposed recommendations and current relevant treatment guidelines,
including the National Institute for Clinical Excellence (NICE)
Schizophrenia Guideline (National Institute for Clinical
Excellence, 2002) are discussed.
Recent prevalence studies reveal that up to a quarter of
psychiatric in-patients are prescribed a high dose of antipsychotic
medication, with the highest prevalence figures being found in
psychiatric intensive care units, rehabilitation wards and forensic
units. There are only limited data on the frequency of prescription
of high-dose antipsychotics in psychiatric patients receiving care
in the community.
The results of the published trials of high-dose antipsychotic
medication for treatment-resistant schizophrenia provide no
evidence to support such a strategy. On the basis of current
evidence, high-dose prescribing, either with a single agent or
combined antipsychotics, should rarely be used and then only for a
time-limited trial in treatment-resistant schizophrenia after all
evidence-based approaches have been shown to be unsuccessful or
inappropriate.
Antipsychotic drugs are commonly prescribed in combination for
those with a psychotic illness who have shown a lack of a
satisfactory response to a single antipsychotic. While the limited
research conducted fails to demonstrate convincing benefits for
such a strategy, there is evidence that combined antipsychotics are
associated with an increased risk of adverse effects and
pharmacokinetic interactions. However, there is some support for
the addition of a second antipsychotic to clozapine in people with
treatmentresistant schizophrenia for whom clozapine alone has
proved insufficiently effective.
High-doses of antipsychotic medication are sometimes used for
rapid tranquillisation, persistent aggression and to reduce the
risk of relapse. However, there is a paucity of research evidence
specifically examining the efficacy and safety of high doses for
rapid tranquillisation. There is no convincing evidence base for
the use of high-dose antipsychotic medication in the management of
persistent aggression associated with psychosis, or for relapse
prevention in psychosis. Relapse prevention studies have tended not
to study high-dosage regimens, but rather have examined
standard-dose regimens, and low-dose and intermittent, targeted
treatment strategies.
A possible link has been postulated between antipsychotic
drugs and ventricular tachycardia and sudden death but no consensus
has been achieved on the frequency of these events, the
contribution of high dosage, or even whether a true causal
association exists. To reduce the risk of arrhythmia, all patients
should be assessed (including electrocardiography) for
cardiovascular disease prior to the institution of antipsychotic
drug therapy. Periodic monitoring of the electrocardiogram (ECG),
and electrolytes during therapy is advocated when high-dose
antipsychotic drug treatment is used.
The Consensus Working Group makes 22 recommendations,
including some under the areas of aggression with psychosis and
that of rapid tranquillisation and treatment-resistant
psychosis.