For patients with schizophrenia, how effective is Clozapine augmentation compared to Clozapine alone, for improving patient outcomes?
The studies included in this summary
found that clozapine augmentation is more effective the clozapine
alone for reducing schizophrenia symptoms. Although there have been
a few studies completed in this area, they were all fairly small
and so it is hard to generalise the results. More, larger studies
should be completed to provide more understanding in this
The National Institute for
Health and Care Excellence guideline, 'Psychosis and schizophrenia
in adults: treatment and management' (2014), makes the following
recommendations on the use of Clozapine augmentation for people
"For people with schizophrenia
whose illness has not responded adequately to clozapine at an
optimised dose, healthcare professionals should consider
recommendation 18.104.22.168 (including measuring therapeutic drug
levels) before adding a second antipsychotic to augment treatment
with clozapine. An adequate trial of such an augmentation may need
to be up to 8-10 weeks. Choose a drug that does not compound the
common side effects of clozapine." (pp178)
The Scottish Intercollegiate
Guidelines Network guideline, 'Management of schizophrenia' (2013),
makes the following recommendations on the topic:
"A systematic review identified six
small RCTs (n=252) of clozapine augmentation. Trials were mainly
short term with the longest being 12 weeks. Response was defined as
a greater than 20% improvement in PANSS or BPRS scores.
Augmentation of clozapine with an antipsychotic (aripiprazole,
risperidone or sulpiride) improved symptoms particularly in those
receiving treatment for longer than ten weeks.
A meta-analysis of double blinded
randomised controlled trials of clozapine augmentation identified
10 studies examining augmentation with antipsychotics. In a small
study (n=28) of sulpiride augmentation there was a significant
effect with respect to BPRS/PANNS (SMD 0.83, 95% CI 0.07 to 1.59).
Meta-analysis of augmentation with other antipsychotics resulted in
no statistically significant effects. These findings are in
agreement with previous reviews, many of which encompassed less
rigorous open label studies.
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For related NICE and SIGN guidelines,
follow the links below.