Kelly Deanna L, Buchanan Robert W, Boggs Douglas L, McMahon Robert P, Dickinson Dwight, Nelson Matthew, Gold James M, Ball M Patricia, Feldman Stephanie, Liu Fang, Conley Robert R
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
J Clin Psychiatry. 2009 Apr;70(4):518-25. doi: 10.4088/jcp.08m04358. Epub 2009 Apr 7.
Currently available antipsychotic medications offer only modest, if any, effects on cognitive performance in people with schizophrenia. Treatments that would improve these impairments could lead to better functional outcomes. Atomoxetine is a nonstimulant, selective norepinephrine reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder. In animals, it has been shown to increase extracellular levels of acetylcholine and dopamine in cortical and hippocampal regions.
Following a 2-week stabilization period, 32 subjects with DSM-IV-diagnosed schizophrenia or schizoaffective disorder were randomly assigned to atomoxetine (80 mg daily) or placebo for 8 weeks. All subjects were treated with antipsychotic monotherapy (excluding clozapine, aripiprazole, and first-generation antipsychotics). Neuropsychological test performance was the primary outcome variable, and the neuropsychological test battery included measures of attention, motor speed, executive function, processing speed, verbal and visual memory, and working memory (rated at baseline and end point). Symptom and side-effect ratings were performed every 2 weeks. The study was conducted from April 2004 through December 2006.
There were no treatment group differences on the primary study outcome measure (overall mean z-score: Wilcoxon chi(2) = 0.21, df = 1, p = .64); nor was there significant evidence of variation in treatment effects on z-score changes across the individual neuropsychological tests (chi(2) = 8.22, df = 8, p = .41). No between-group differences were noted in symptom changes. Atomoxetine was well tolerated and was associated with a trend for improvement in extrapyramidal side effects relative to placebo (p = .063).
Our results provide further evidence that atomoxetine has limited benefit for improving cognition in people with schizophrenia.
clinicaltrials.gov Identifier: NCT00161031.
目前可用的抗精神病药物对精神分裂症患者的认知能力仅有适度影响（即便有影响的话）。能够改善这些认知障碍的治疗方法可能会带来更好的功能预后。托莫西汀是一种非刺激性的选择性去甲肾上腺素再摄取抑制剂，已被批准用于治疗注意力缺陷/多动障碍。在动物实验中，它已被证明可提高皮质和海马区域的乙酰胆碱和多巴胺细胞外水平。
在为期2周的稳定期后，32名经DSM-IV诊断为精神分裂症或分裂情感性障碍的受试者被随机分配接受托莫西汀（每日80毫克）或安慰剂治疗，为期8周。所有受试者均接受抗精神病单一疗法治疗（不包括氯氮平、阿立哌唑和第一代抗精神病药物）。神经心理学测试表现是主要结局变量，神经心理学测试组合包括注意力、运动速度、执行功能、处理速度、言语和视觉记忆以及工作记忆的测量指标（在基线和终点进行评分）。每2周进行一次症状和副作用评分。该研究于2004年4月至2006年12月进行。
在主要研究结局指标上，治疗组之间没有差异（总体平均z分数：Wilcoxon卡方检验χ(2)=0.21，自由度df = 1，p = 0.64）；在各个神经心理学测试中，也没有显著证据表明治疗效果在z分数变化上存在差异（χ(2)=8.22，自由度df = 8，p = 0.41）。在症状变化方面，未观察到组间差异。托莫西汀耐受性良好，与安慰剂相比，锥体外系副作用有改善趋势（p = 0.063）。
我们的结果进一步证明，托莫西汀对改善精神分裂症患者的认知能力益处有限。
clinicaltrials.gov标识符：NCT00161031。
Zotero 插件