Finkel Sanford I, Mintzer Jacobo E, Dysken Maurice, Krishnan K R R, Burt Tal, McRae Thomas
Department of Psychiatry, University of Chicago Medical School, and the Leonard Schanfield Research Institute at Council for Jewish Elderly, Chicago, IL 60091, USA.
Int J Geriatr Psychiatry. 2004 Jan;19(1):9-18. doi: 10.1002/gps.998.
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.
Patients with probable or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a severity score > or =2 in at least one domain), were treated with donepezil (5-10 mg) 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.
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 40% on placebo (p = 0.006) achieved a response (defined as > or = 50% 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.
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.
探讨舍曲林增效疗法治疗接受多奈哌齐治疗的门诊阿尔茨海默病（AD）患者行为表现的安全性和有效性。
患有可能或疑似AD且神经精神科问卷（NPI）总分>5（至少一个领域的严重程度评分>或=2）的患者接受多奈哌齐（5-10mg）治疗8周，然后随机分配接受为期12周的舍曲林（50-200mg）或安慰剂双盲增效治疗。主要疗效指标为12项神经精神科问卷（NPI）、临床总体印象改善（CGI-I）和严重程度（CGI-S）量表。
24例患者接受多奈哌齐+舍曲林治疗，120例患者接受多奈哌齐+安慰剂治疗。在三个主要疗效指标的终点时均无统计学显著差异。然而，线性混合模型分析发现，多奈哌齐+舍曲林组的CGI-I评分有适度但统计学上显著更大的改善。此外，在患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40%的患者（p = 0.006）达到反应（定义为四项NPI行为子量表降低>或=50%）。与多奈哌齐+安慰剂组相比，多奈哌齐+舍曲林组有1例不良事件（腹泻）显著更常见（p < 0.05）。
在该AD门诊患者样本中，舍曲林增效疗法耐受性良好。此外，事后分析表明舍曲林在混合模型分析中比安慰剂增效有适度但统计学上显著的优势，在患有中度至重度痴呆行为和心理症状的患者亚组中有临床和统计学上显著的优势。
