Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone) compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: Overview of systematic reviews

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Melnik T1, Soares B1, Puga E1, Atallah A1, Rufino C1
1Brazilian Cochrane Center, São Paulo, Brazil

Background: According to some cohort studies, the prevalence of refractory schizophrenia (RS) is 20% to 40%.

Objectives: Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS.

Methods: This was a critical appraisal of Cochrane reviews published in The Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs) on RS. The following databases were searched: MEDLINE (1966-2009), CENTRAL: Controlled Trials of the Cochrane Collaboration (2009, Issue 2), EMBASE (1980-2009), LILACS (1982-2009). There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included.

Results: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences among the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, such asamisulpride, clozapine and olanzapine.

Conclusions: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.