Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
J Clin Psychopharmacol. 2012 Oct;32(5):593-601. doi: 10.1097/JCP.0b013e3182664cfc.
Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n = 24, titrated up to 150 mg/d) or placebo (n =24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-Åsberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time × group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-Åsberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.
精神分裂症认知障碍与社会心理功能不良相关。有几方面的证据表明内质网蛋白 sigma-1 受体参与了精神分裂症患者的认知障碍，sigma-1 受体激动剂氟伏沙明在精神分裂症动物模型和部分精神分裂症患者中治疗认知障碍有效。进行了一项氟伏沙明辅助治疗精神分裂症患者的随机、双盲、安慰剂对照、平行试验。共纳入 48 例慢性精神分裂症患者。受试者被随机分为氟伏沙明附加治疗组（n = 24，滴定至 150 mg/d）或安慰剂组（n = 24），进行为期 12 周的双盲试验。主要结局测量指标是剑桥神经心理学测试自动电池（CANTAB），评估视觉记忆、工作记忆、注意力和执行功能。次要结局测量指标是阳性和阴性综合征量表、阴性症状评定量表、生活质量量表和蒙哥马利-阿斯伯格抑郁评定量表。氟伏沙明耐受性良好。在 CANTAB、阳性和阴性综合征量表、阴性症状评定量表、生活质量量表或蒙哥马利-阿斯伯格抑郁评定量表的评分中，均未观察到时间×组间交互作用的显著影响。然而，在二次分析中，CANTAB 的空间工作记忆策略评分（执行功能）从基线到终点的变化在氟伏沙明组中有所改善。本研究提示氟伏沙明辅助治疗对改善精神分裂症患者的认知障碍没有显著益处。然而，需要更大样本量的进一步研究来证实二次分析结果。
