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This industry-independent, multicentre, assessor-blinded randomized trial compared seven antipsychotics in acutely ill patients with schizophrenia across 32 hospitals. A total of 3,067 patients aged 18–45 years were randomized to 6 weeks of flexible-dose monotherapy with olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol; 82% completed follow-up. Significant between-group differences were observed in percentage change in Positive and Negative Syndrome Scale scores. At week 6, olanzapine and risperidone produced greater symptom improvement than aripiprazole, ziprasidone and quetiapine, with mean differences ranging from 5.52 to 7.93 percentage points, but did not differ significantly from haloperidol or perphenazine. Olanzapine had the highest relative risk of weight gain (1.44–3.22), whereas aripiprazole had a lower risk of hyperprolactinaemia than all other agents (relative risks, 0.11–0.21) and was least sedating. Ziprasidone and aripiprazole were associated with lower risks of weight gain and metabolic adverse effects. Haloperidol had a higher risk of extrapyramidal symptoms, while olanzapine and risperidone were associated with lower all-cause discontinuation rates than ziprasidone and haloperidol (hazard ratios, 0.61–0.73). The authors concluded that the trial clarifies comparative efficacy and adverse-effect profiles, supporting more evidence-informed antipsychotic selection.
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This industry-independent, multicentre, assessor-blinded randomized trial compared seven antipsychotics in acutely ill patients with schizophrenia across 32 hospitals. A total of 3,067 patients aged 18–45 years were randomized to 6 weeks of flexible-dose monotherapy with olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol; 82% completed follow-up. Significant between-group differences were observed in percentage change in Positive and Negative Syndrome Scale scores. At week 6, olanzapine and risperidone produced greater symptom improvement than aripiprazole, ziprasidone and quetiapine, with mean differences ranging from 5.52 to 7.93 percentage points, but did not differ significantly from haloperidol or perphenazine. Olanzapine had the highest relative risk of weight gain (1.44–3.22), whereas aripiprazole had a lower risk of hyperprolactinaemia than all other agents (relative risks, 0.11–0.21) and was least sedating. Ziprasidone and aripiprazole were associated with lower risks of weight gain and metabolic adverse effects. Haloperidol had a higher risk of extrapyramidal symptoms, while olanzapine and risperidone were associated with lower all-cause discontinuation rates than ziprasidone and haloperidol (hazard ratios, 0.61–0.73). The authors concluded that the trial clarifies comparative efficacy and adverse-effect profiles, supporting more evidence-informed antipsychotic selection.
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