Abstract：
BACKGROUND: The aim of the study was to evaluate interaction effect of various augmentation strategies with clozapine in patients with Treatment-resistant schizophrenia.
METHODS: Data was extracted for change in positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS) scores for monotherapy with various antipsychotic agents alone and their combination with clozapine. Individual patient data was generated using simulation of data (factorial trial framework) from published clinical trials for sample sizes from eight to 400 to evaluate interaction effect through linear modeling. Dose equivalents were calculated, and best fit models were determined for simulated data.
RESULTS: The polynomial model was found to be the best fit for the simulated data to determine interaction effect of combination. The clozapine augmentation with risperidone and ziprasidone was found to be antagonistic, whereas it was additive for haloperidol, aripiprazole, and quetiapine. A synergistic effect was observed for ECT combined with clozapine (Interaction effect: -7.62; p <0.001). A sample size of 250-300 may be sufficient to demonstrate a clinically significant interaction in future trials.
CONCLUSIONS: Clozapine may be augmented with electroconvulsive therapy, leading to the enhancement of antipsychotic effect. Though some antipsychotics like aripiprazole demonstrate additive effects, they may also add to the adverse effects.
METHODS: Data was extracted for change in positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS) scores for monotherapy with various antipsychotic agents alone and their combination with clozapine. Individual patient data was generated using simulation of data (factorial trial framework) from published clinical trials for sample sizes from eight to 400 to evaluate interaction effect through linear modeling. Dose equivalents were calculated, and best fit models were determined for simulated data.
RESULTS: The polynomial model was found to be the best fit for the simulated data to determine interaction effect of combination. The clozapine augmentation with risperidone and ziprasidone was found to be antagonistic, whereas it was additive for haloperidol, aripiprazole, and quetiapine. A synergistic effect was observed for ECT combined with clozapine (Interaction effect: -7.62; p <0.001). A sample size of 250-300 may be sufficient to demonstrate a clinically significant interaction in future trials.
CONCLUSIONS: Clozapine may be augmented with electroconvulsive therapy, leading to the enhancement of antipsychotic effect. Though some antipsychotics like aripiprazole demonstrate additive effects, they may also add to the adverse effects.
摘要：
背景：该研究的目的是评估各种增强策略与氯氮平在难治性精神分裂症患者中的相互作用效果。
方法：提取了单独使用各种抗精神病药及其与氯氮平联合使用的阳性和阴性综合征量表（PANSS）或简短精神病学评定量表（BPRS）评分变化的数据。使用来自已发表的临床试验的数据模拟（阶乘试验框架）生成个体患者数据，样本量为8至400，以通过线性建模评估相互作用效果。计算剂量当量，并为模拟数据确定了最佳拟合模型。
结果：发现多项式模型是模拟数据的最佳拟合，以确定组合的相互作用效应。发现利培酮和齐拉西酮的氯氮平增强作用具有拮抗作用，而它是氟哌啶醇的添加剂，阿立哌唑,还有喹硫平.观察到ECT与氯氮平组合的协同作用(相互作用作用:-7.62;p<0.001)。250-300的样本量可能足以证明在未来的试验中具有临床意义的相互作用。
结论：氯氮平可以通过电惊厥治疗增强，导致抗精神病作用的增强。尽管一些抗精神病药物如阿立哌唑表现出累加效应，它们也可能增加不利影响。
方法：提取了单独使用各种抗精神病药及其与氯氮平联合使用的阳性和阴性综合征量表（PANSS）或简短精神病学评定量表（BPRS）评分变化的数据。使用来自已发表的临床试验的数据模拟（阶乘试验框架）生成个体患者数据，样本量为8至400，以通过线性建模评估相互作用效果。计算剂量当量，并为模拟数据确定了最佳拟合模型。
结果：发现多项式模型是模拟数据的最佳拟合，以确定组合的相互作用效应。发现利培酮和齐拉西酮的氯氮平增强作用具有拮抗作用，而它是氟哌啶醇的添加剂，阿立哌唑,还有喹硫平.观察到ECT与氯氮平组合的协同作用(相互作用作用:-7.62;p<0.001)。250-300的样本量可能足以证明在未来的试验中具有临床意义的相互作用。
结论：氯氮平可以通过电惊厥治疗增强，导致抗精神病作用的增强。尽管一些抗精神病药物如阿立哌唑表现出累加效应，它们也可能增加不利影响。
