Randomized controlled study of the T-type calcium channel antagonist MK-8998 for the treatment of acute psychosis in patients with schizophrenia
Randomized controlled study of the T-type calcium channel antagonist MK-8998 for the treatment of acute psychosis in patients with schizophrenia
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DOI：
10.1002/hup.2289
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发表时间：
2013-03-01
影响因子：
1.7
通讯作者：
Michelson, David
中科院分区：
文献类型：
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作者：
Egan, Michael F.;Zhao, Xin;Michelson, David
目的 探讨T型钙通道拮抗剂MK-8998治疗精神分裂症患者急性精神病是否有效。方法 这是一项随机、双盲、平行组研究。在安慰剂导入后，患有精神分裂症的急性精神病住院患者被随机分为为期 4 周的 MK-8998 12/16 mg 每日治疗组 (N=86)、奥氮平 10/15 mg 每日治疗组 (N=47) 或安慰剂治疗组 (N=83)。主要疗效指标是阳性和阴性症状量表（PANSS）评分。结果 在 216 名随机患者中，158 名完成了为期 4 周的研究：MK-8998=58（67.4%），奥氮平=38（80.9%），安慰剂=62（74.7%）。 MK-8998 和奥氮平在第 4 周时 PANSS 评分相对于基线的平均变化与安慰剂没有显着差异：MK-8998 安慰剂差异=0.6 [95% 置信区间 (CI): 7.0, 5.8]，p=0.9；奥氮平安慰剂差异=4.3 [95% CI: 11.7, 3.1)，p=0.3。应答率分析（PANSS 评分较基线提高 20%）表明奥氮平优于安慰剂（比值比=2.20 [95% CI: 0.95, 5.09], p=0.07），但 MK-8998 与安慰剂相比没有效果（比值比=1.28 [95% CI: 0.62, 2.64], p=0.5）。治疗总体耐受性良好，但报告 MK-8998 (47.7%) 和奥氮平 (48.9%) 不良事件的患者多于安慰剂 (37.3%)。结论 根据第 4 周的 PANSS 评分，MK-8998 对治疗患有精神分裂症的急性精神病患者无效。由于活性对照药的疗效有限，我们不能排除 T 型钙通道拮抗剂可能被证明对精神分裂症有效的可能性。版权所有 (c) 2013 John Wiley & Sons, Ltd.
Objective This study aimed to evaluate whether the T-type calcium channel antagonist MK-8998 was effective in treating acute psychosis in patients with schizophrenia. Methods This was a randomized, double-blind, parallel-group study. After a placebo lead-in, acutely psychotic inpatients with schizophrenia were randomized to 4weeks of MK-8998 12/16mg daily (N=86), olanzapine 10/15mg daily (N=47), or placebo (N=83). The primary efficacy measure was score on the Positive and Negative Syndrome Scale (PANSS). Results Out of 216 randomized patients, 158 completed the 4-week study: MK-8998=58 (67.4%), olanzapine=38 (80.9%), and placebo=62 (74.7%). The mean changes from baseline in PANSS score at week 4 for MK-8998 and olanzapine were not significantly different from placebo: MK-8998placebo difference=0.6 [95% confidence interval (CI): 7.0, 5.8], p=0.9; olanzapineplacebo difference=4.3 [95% CI: 11.7, 3.1), p=0.3. A responder rate analysis (20% improvement from baseline in PANSS score) suggested an advantage of olanzapine over placebo (odds ratio=2.20 [95% CI: 0.95, 5.09], p=0.07) but no effect of MK-8998 over placebo (odds ratio=1.28 [95% CI: 0.62, 2.64], p=0.5). Treatments were generally well tolerated, but more patients reported adverse events for MK-8998 (47.7%) and olanzapine (48.9%) than placebo (37.3%). Conclusions MK-8998 was not effective in treating acutely psychotic inpatients with schizophrenia, as measured by PANSS score at week 4. Because of the limited efficacy of the active comparator, we cannot exclude the possibility that T-type calcium channel antagonists could prove to be effective in schizophrenia. Copyright (c) 2013 John Wiley & Sons, Ltd.