A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil
A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil
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DOI：
10.1002/gps.998
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
McRae, T
中科院分区：
文献类型：
--
作者：
Finkel, SI;Mintzer, JE;McRae, T
目的探讨舍曲林强化治疗对门诊多奈哌齐治疗的阿尔茨海默病（AD）患者行为学表现的安全性和有效性。方法选择临床诊断为AD，神经精神量表（NPI）总分>5分的患者（在至少一个领域中严重性评分大于或等于2），用多奈哌齐（5- 10 mg）治疗8周，然后随机分配到12周的双盲增强治疗，使用舍曲林（50-200 mg）或安慰剂。主要疗效指标为12项神经精神量表（NPI）和临床总体印象改善（CGI-I）和严重程度（CGI-S）scales.Results多奈哌齐+舍曲林组24例，多奈哌齐+安慰剂组120例。在终点时，三个主要疗效指标中的任何一个均无统计学显著性差异。然而，线性混合模型分析发现，多奈哌齐+舍曲林的CGI-I评分有适度但统计学显著性更大的改善。此外，在一个有中度至重度痴呆行为和心理症状的患者亚组中，舍曲林组60%的患者与安慰剂组46%的患者（p = 0.006）达到了反应（定义为四项NPI行为子量表减少大于或等于50%）。一个不良事件（腹泻）是显着（p < 0.05）更常见的多奈哌齐+舍曲林组相比，多奈哌齐+安慰剂group.Conclusion舍曲林增强是耐受性良好的AD门诊患者的样本。此外，事后分析表明，舍曲林在混合模型分析中与安慰剂增强相比具有适度但统计学显著的优势，在中度至重度痴呆行为和心理症状患者亚组中具有临床和统计学显著优势。版权所有（C）2004约翰威利父子有限公司。
Objective To examine the safety and efficacy of sertraline augmentation therapy in the treatment of behavioral manifestations of Alzheimer's disease (AD) in outpatients treated with donepezil.Methods and materials Patients with probable or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a severity score greater than or equal to2 in at least one domain), were treated with donepezil (5-10mg) for 8 weeks, then randomly assigned to 12 weeks of double-blind augmentation therapy with either sertraline (50-200 mg) or placebo. Primary efficacy measures were the 12-item Neuropsychiatric Inventory (NPI) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales.Results 24 patients were treated with donepezil + sertraline and 120 patients with donepezil + placebo. There were no statistically significant differences at endpoint on any of the three primary efficacy measures. However, a linear mixed model analysis found modest but statistically significantly greater improvements in the CGI-I score on donepezil + sertraline. Moreover, in a sub-group of patients with moderate-to-severe behavioral and psychological symptoms of dementia, 60% of patients on sertraline vs 46% on placebo (p = 0.006) achieved a response (defined as greater than or equal to50% reduction in a four-item NPI-behavioral subscale). One adverse event (diarrhea) was significantly (p < 0.05) more common in the donepezil + sertraline group compared to the donepezil + placebo group.Conclusion Sertraline augmentation was well-tolerated in this sample of AD outpatients. In addition, post hoc analyses demonstrated a modest but statistically significant advantage of sertraline over placebo augmentation in mixed model analyses and a clinically and statistically significant advantage in a subgroup of patients with moderate-to-severe behavioral and psychological symptoms of dementia. Copyright (C) 2004 John Wiley Sons, Ltd.