A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.
A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.
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DOI：
10.1016/j.biopsych.2010.09.052
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发表时间：
2011-03-01
影响因子：
10.6
通讯作者：
Marder, Stephen R.
中科院分区：
文献类型：
--
作者：
Buchanan, Robert W.;Keefe, Richard S. E.;Lieberman, Jeffrey A.;Barch, Deanna M.;Csernansky, John G.;Goff, Donald C.;Gold, James M.;Green, Michael F.;Jarskog, L. Fredrik;Javitt, Daniel C.;Kimhy, David;Kraus, Michael S.;McEvoy, Joseph P.;Mesholam-Gately, Raquelle I.;Seidman, Larry J.;Ball, M. Patricia;McMahon, Robert P.;Kern, Robert S.;Robinson, James;Marder, Stephen R.
在之前的一项初步研究中，MK-0777（一种GABAA α2/α3部分激动剂）被报告可改善精神分裂症患者的延迟记忆和前额叶皮质功能的认知测量。本研究旨在进一步检查MK-0777治疗精神分裂症认知障碍的疗效和安全性。60名患有DSM-IV精神分裂症的患者参加了一项为期4周的多中心、双盲、安慰剂对照、随机临床试验。受试者被随机分配至：MK-0777 3 mg BID（n=18）; MK-0777 8 mg BID（n=21）;或安慰剂（n=21）。受试者的临床表现稳定。使用MATRICS共识认知成套测验（MCCB）、AX-CPT和N-Back评估认知。UCSD基于表现的技能评估-2（UPSA-2）和精神分裂症认知评定量表（SCoRS）评估功能能力，并作为功能结局的共同主要指标。在主要结局指标MCCB综合评分方面，没有显著的组间差异。次要分析表明，随机分配至安慰剂组的受试者在视觉记忆和推理/解决问题测试中的表现显著优于分配至任一MK-0777剂量组的受试者。AX-CPT或N-Back d prime评分或UPSA-2和SCoRS总分无显著组间差异。一般而言，MK-0777耐受性良好，副作用极小。研究结果表明，MK-0777对精神分裂症患者的认知障碍几乎没有好处。GABAA受体仍然是一个有希望的靶点，但可能需要一种在GABAA α2位点具有更大内在活性的更有效的部分激动剂来增强精神分裂症的认知能力。
In a previous pilot study, MK-0777, a GABAA α2/α3 partial agonist, was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schizophrenia. Sixty people with DSM-IV schizophrenia entered a 4-week, multi-center, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized to either: MK-0777 3mg BID (n=18); MK-0777 8mg BID (n=21); or placebo (n=21). Participants were clinically stable. The MATRICS Consensus Cognitive Battery (MCCB), AX-CPT and N-Back were used to assess cognition. The UCSD Performance Based Skills Assessment-2 (UPSA-2) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity and served as functional outcome co-primary measures. There were no significant group differences on the primary outcome measure, the MCCB composite score. Secondary analyses suggested that participants randomized to placebo performed significantly better on visual memory and reasoning/problem-solving tests than participants assigned to either MK-0777 dose. There were no significant group differences on the AX-CPT or N-Back d prime scores or UPSA-2 and SCoRS total scores. In general, MK-0777 was well tolerated with minimal side effects. The study results suggest that MK-0777 has little benefit for cognitive impairments in people with schizophrenia. The GABAA receptor remains a promising target, but a more potent partial agonist with greater intrinsic activity at the GABAA α2 site may be needed for cognitive enhancement in schizophrenia.
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影响因子：
6.6
作者：
Buchanan, RW;Davis, M;Marder, SR
通讯作者：
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