Divalproex ER Combined with Olanzapine or Risperidone for Treatment of Acute Exacerbations of Schizophrenia
Divalproex ER Combined with Olanzapine or Risperidone for Treatment of Acute Exacerbations of Schizophrenia
复制标题
DOI：
10.1038/npp.2008.209
复制
发表时间：
2009-04-01
影响因子：
7.6
通讯作者：
Saltarelli, Mario
中科院分区：
文献类型：
--
作者：
Casey, Daniel E.;Daniel, David G.;Saltarelli, Mario
本研究的目的是评估双丙戊酸钠缓释剂（双丙戊酸钠 ER）与安慰剂相比，与奥氮平或利培酮联合治疗精神分裂症急性加重的疗效和安全性。在这项为期12周的随机、双盲、平行组、多中心试验中，共有402名患者接受了随机分组和治疗； 103 名患者接受奥氮平/安慰剂，99 名患者接受奥氮平/双丙戊酸缓释片，101 名患者接受利培酮/安慰剂，99 名患者接受利培酮/双丙戊酸缓释片。双丙戊酸钠缓释剂在第 1 天开始，每天上午 20 mg/kg，并在第 3、7 和 10 天滴定至临床效果，最大剂量不超过每天 35 mg/kg。奥氮平和利培酮分别以 5 毫克/天和 2 毫克/天每晚开始服用，第 3 天增加至 10 毫克/天和 4 毫克/天，并在第 6 天增加至固定目标剂量 15 毫克/天和 6 毫克/天。在阳性和阴性症状量表上进行的从基线到第 14 天最后一次观察的平均变化的主要疗效变量方面，联合治疗组和抗精神病药物单药治疗组之间没有显示显着的治疗差异。 （PANSS）总分，尽管抗精神病药物单一疗法确实在几个时间点的 PANSS 阴性子量表上表现出优于联合疗法。第 84 天时，联合治疗在 PANSS 总分上也未能显示出优于抗精神病药物单一治疗的优势。研究中观察到的大多数不良事件的严重程度为轻度至中度，联合治疗组和相应的抗精神病药物单一治疗组之间的不良事件总数没有显着差异。
The objective of this study was to evaluate the efficacy and safety of divalproex sodium extended release (divalproex ER) vs placebo in combination with olanzapine or risperidone for the treatment of acute exacerbations of schizophrenia. In this 12-week, randomized, double-blind, parallel-group, multi-center trial, a total of 402 patients were randomized and treated; 103 received olanzapine/placebo, 99 received olanzapine/divalproex ER, 101 received risperidone/placebo, and 99 received risperidone/divalproex ER. Divalproex ER was initiated on day 1 at 20 mg/kg per day q AM and was titrated to clinical effect on days 3, 7, and 10, not to exceed a maximum dosage of 35 mg/kg per day. Olanzapine and risperidone were initiated at 5 and 2 mg/day q PM, respectively, increased to 10 and 4 mg/day on day 3, and increased to fixed target doses of 15 and 6 mg/day on day 6. No significant treatment difference was demonstrated between the combination therapy and antipsychotic monotherapy groups on the primary efficacy variable of the mean change from baseline to day 14 last observation carried forward on the Positive and Negative Syndrome Scale (PANSS) total score, although antipsychotic monotherapy did demonstrate superiority to combination therapy on the PANSS Negative subscale at several time points. Combination therapy also failed to show an advantage over antipsychotic monotherapy at day 84 on the PANSS total score. Most adverse events observed in the study were mild to moderate in severity, and the overall number of adverse events did not differ significantly between the combination therapy groups and their corresponding antipsychotic monotherapy group.