Combination of clozapine with an atypical antipsychotic: a meta-analysis

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Purpose The purpose of this paper is to review the efficacy of atypical antipsychotics in combination with clozapine. Previous meta-analyses have assessed the use of both typical and atypical antipsychotics in combination with clozapine, combination treatment being withheld only for those patients deemed treatment resistant. Design/methodology/approach Outcomes assessed included: positive, negative and overall symptom score. The total numbers of participants (n=588) were scored using the Positive and Negative Symptom Scale/the Brief Psychiatric Rating Scale and effect sizes were used to judge the efficacy of the combination treatments. Data gained from the ten randomized, double blind, placebo controlled trials were analysed using the R statistical software. Findings The effect sizes gained from analysis showed a small benefit of combination therapy over clozapine monotherapy. Therefore, it is the recommendation of this analysis that alternative avenues be sought in order to treat patients who have a sub-optimal response to clozapine with a combination other than two second generation antipsychotics. Research limitations/implications The initial trials search unveiled 1,412 studies. After the inclusion and exclusion criteria were applied, ten trials were used in this meta-analysis. Practical implications The recommendation of this analysis that alternative medications be sought in order to treat patients who have a sub-optimal response to clozapine with a combination other than two second generation antipsychotics. This route should only be used once all other treatment options have been exhausted. Originality/value This meta-analytical study looks specifically at the combination of atypical antipsychotics with clozapine in comparison to clozapine monotherapy. This work extends existing meta-analysis by incorporating data from more recent trials.