Question:
In adults with treatment resistant schizophrenia (with or without mild learning disabilities), how effective are antipsychotic combinations, compared to any other intervention, in improving patient outcomes?
Answer:
Plain language summary
Research evidence suggests that combining antipsychotic
medications may have some benefit to those with treatment resistant
schizophrenia; however this evidence available is weak with no
clear indication as to which combinations are most effective. More
rigorous controlled studies need to be carried out before any
definite conclusions or recommendations can be made. No studies
were identified looking at combination antipsychotics for patients
with treatment resistant schizophrenia and a learning
disability.
Clinical and research implications
No definite clinical implications may be made based on the
evidence included in this BEST summary. There is weak evidence to
suggest that various combined treatments may show some improved
outcomes in patients with clozapine-resistant schizophrenia
compared with placebo, but there is no strong evidence to suggest
which combination strategies are superior to others. There is
consensus among all of the included reviews/studies that more high
quality randomised controlled trials, with adequate sample sizes,
are needed before firms recommendations can be made about clozapine
augmentation strategies. One of the review authors also
suggested that these trials should also measure global outcomes
such as 'healthy days', 'social functioning', 'satisfaction with
treatment', 'ability to live and work in the community', and
compliance.
What do guidelines say?
The Scottish Intercollegiate Guidelines Network (SIGN)
recommends that a trial of clozapine augmentation with a second SGA
(Second Generation Antipsychotic) should be considered for service
users whose symptoms have not responded adequately to clozapine
alone, despite dose optimisation. Treatment should be continued for
a minimum of ten weeks.
"5.7.2 Clozapine augmentation with
another antipsychotic: 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.112 These findings are in agreement with previous reviews,
many of which encompassed less rigorous open label studies"
To view the full summary, click the Download
Documentlink to the right
To view the Cochrane review, click the link under Related
Documents below.
For related SIGN guidelines,
follow the links below