Background and Hypothesis Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situation. Study Design In total, 327 inpatients with an acute exacerbation of schizophrenia were randomized to double-blind treatment with either olanzapine (5–20 mg/day) or amisulpride (200–800 mg/day). Those patients who had not reached at least 25% Positive-and-Negative-Syndrome-Scale (PANSS) total score reduction from baseline after 2 weeks (the “non-improvers”) were rerandomized double-blind to either staying on the same compound (“stayers”) or to switching to the other antipsychotic (“switchers”) for another 6 weeks. The primary outcome was the difference in the number of patients in symptomatic remission between the combined “switchers” and the “stayers” after 8 weeks of treatment, analyzed by logistic regression. Study Results A total of 142 nonimprovers were rerandomized at week two. 25 (45.5 %) of the ‘stayers' compared to 41 (68.3 %) of the “switchers” reached remission at endpoint (p = .006). Differences in secondary efficacy outcomes were not significant, except for the PANSS negative subscore and the Clinical-Global-Impression-Scale. “Switchers” and “stayers” did not differ in safety outcomes. Conclusions Switching “non-improvers” from amisulpride to olanzapine or vice-versa increased remission rates and was safe. The superiority in the primary outcome was, however, not paralleled by significant differences in most secondary efficacy outcomes and the effect was only apparent at the last visit making replications of longer duration necessary.

中文翻译：

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将早期无改善的抗精神病药物改为氨磺必利或奥氮平：精神分裂症患者的随机、双盲试验

背景和假设荟萃分析表明，大多数在抗精神病药物治疗两周后没有改善的精神分裂症患者随后不太可能完全缓解。我们假设在这种情况下改用另一种具有不同受体结合谱的抗精神病药是一种有效的策略。研究设计 总共 327 名精神分裂症急性加重住院患者被随机分配接受奥氮平（5-20​​ 毫克/天）或氨磺必利（200-800 毫克/天）双盲治疗。两周后阳性与阴性症状量表 (PANSS) 总分较基线降低至少 25% 的患者（“非改善者”）被重新随机双盲分配，要么继续使用相同的化合物（“留存者”）或改用另一种抗精神病药物（“转换者”）另外 6 周。主要结局是治疗 8 周后，联合“转换者”和“停留者”之间症状缓解的患者数量差异，通过逻辑回归进行分析。研究结果 共有 142 名无改善者在第二周被重新随机分组。25 名 (45.5 %) 的“停留者”在终点时达到缓解，而 41 名 (68.3 %) 的“转换者”达到缓解 (p = .006)。除 PANSS 阴性子评分和临床整体印象量表外，次要疗效结果的差异并不显着。“切换者”和“停留者”在安全结果上没有差异。结论 将“非改善药物”从氨磺必利换为奥氮平（反之亦然）可提高缓解率并且是安全的。然而，主要结果的优越性与大多数次要疗效结果的显着差异并不平行，并且效果仅在最后一次访视时才明显，因此需要更长的持续时间进行重复。