Question: 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 area.

 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 with schizophrenia:

 "For people with schizophrenia whose illness has not responded adequately to clozapine at an optimised dose, healthcare professionals should consider recommendation (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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