First-Episode Schizophrenia: Searching for the Most Effective Atypical Antipsychotic

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Researchers examined which atypical antipsychotic was more effective and safe in first-episode drug-naive schizophrenia.

Aripiprazole, risperidone, quetiapine, olanzapine, and ziprasidone had significant curative effects on first-episode drug-naive schizophrenia, according to an article published in the Annals of General Psychiatry. Although risperidone was more effective than aripiprazole and olanzapine in treating schizophrenia, quetiapine and olanzapine resulted in less severe extrapyramidal adverse effects than ziprasidone.

The open-label study, conducted by Congjie Wang from the Department of Psychiatry, No. 3 People’s Hospital and Teaching Hospital of Xuzhou Medical University in Huai’an, Jiangsu, China, and colleagues, included 200 inpatients with first-episode drug-naive schizophrenia. Patients were randomly assigned to 6 to 8 weeks of treatment with 1 of the 5 atypical antipsychotics from October 2012 to November 2014. The investigators evaluated efficacy, acceptability, and safety by the reduction of the Brief Psychiatric Rating Scale total score, the proportion of treatment discontinuation, and adverse events.

The authors reported that Brief Psychiatric Rating Scale total scores had significantly decreased by the end of the study (P <.01). Significant-between group differences for efficacy were noted only in the comparisons of risperidone with aripiprazole and olanzapine. The reduction in BPRS scores was significantly greater for patients treated with risperidone than for those in the aripiprazole (P <.01) and olanzapine (P <.05) groups after controlling for the effect of the differences in age of onset.

There was also a significant difference between quetiapine (P =.019), olanzapine (P =.018), and ziprasidone for the proportion of patients continuing to receive the initially allocated therapy, with a greater percentage of ziprasidone-treated patients discontinuing initial therapy (63%) than either quetiapine-treated (31%) or olanzapine-treated (40%) patients. Women were also more likely to discontinue therapy than men (P =.002). Extrapyramidal symptoms occurred less often with quetiapine and olanzapine than with the other 3 antipsychotics (P <.05), but no significant differences were noted for other adverse events between the medication groups.

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Given the higher discontinuation rate for ziprasidone and the lower rate of extrapyramidal effects with quetiapine and olanzapine, the authors concluded that quetiapine and olanzapine are superior to ziprasidone, but risperidone is more effective than aripiprazole and olanzapine in reducing the Brief Psychiatric Rating Scale score.

The open-label design of the trial made it prone to bias, and the concomitant use of other medications made judging the efficacy difficult. Furthermore, because of noncompliance and drop-out, the number of patients enrolled in the ziprasidone group was smaller than in the other medication groups.


Wang C, Shi W, Huang C, Zhu J, Huang W, Chen G. The efficacy, acceptability, and safety of five atypical antipsychotics in patients with first-episode drug-naïve schizophrenia: a randomized comparative trial. Ann Gen Psychiatry. 2017;16:47.