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Review: limited evidence that adding a second antipsychotic improves clozapine treatment in schizophrenia

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What is the effect of adding antipsychotics to clozapine in people with schizophrenia? Does absence of double blindness exaggerate estimates of treatment effect?


Standardised mean difference of group mean changes in the Positive and Negative Symptoms Scale or the Brief Psychiatric Rating Scale score, either from baseline to endpoint or at the end of the trial; treatment failure, defined as the proportion of people with no clinically significant response in global state.



Systematic review with meta-analysis.

Data sources:

Cochrane Schizophrenia Group Trials Register, MEDLINE and EMBASE were searched from inception to November 2007 for randomised controlled trials (RCTs). Reference lists of identified studies were hand searched.

Study selection and analysis:

Two reviewers appraised studies and selected RCTs comparing clozapine plus placebo or clozapine alone with clozapine plus another antipsychotic in adults (aged 18 years and over) with a diagnosis of schizophrenia or related disorders. There were no language restrictions. Participants had psychotic symptoms that had not responded to optimal doses of clozapine alone …

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  • Source of funding Fondazione Cariverona.


  • Competing interests FG has a family member with professional links to and share holdings in Eli Lilly and GSK, and has received funding from various different pharmaceutical companies.

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