De Deyn Peter Paul, Carrasco Manuel Martín, Deberdt Walter, Jeandel Claude, Hay Donald P, Feldman Peter D, Young Carrie A, Lehman Deborah L, Breier Alan
Department of Neurology, Middelheim Hospital, University of Antwerp, Antwerp, Belgium.
Int J Geriatr Psychiatry. 2004 Feb;19(2):115-26. doi: 10.1002/gps.1032.
Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings.
Patients (n = 652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5 mg/day).
Mean age was 76.6+/-10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items-primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5 mg olanzapine group (-6.2 +/- 4.9) was significantly greater than with placebo (-5.0 +/- 6.1, p = 0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz 2.5 olanzapine group (2.8 +/- 1.4, p = 0.030) relative to placebo (3.2 +/- 1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol.
While 1.0 mg olanzapine did not show significant differences from placebo, the 2.5 mg dose was a reasonable starting dose. Olanzapine at 7.5 mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated.
精神病性症状和行为障碍是老年阿尔茨海默病（AD）患者护理中的一个关注点。本研究旨在比较奥氮平与安慰剂在长期或持续护理环境中患有与AD相关的精神病性症状患者中的疗效。
患有AD且有妄想或幻觉的患者（n = 652）被随机分配接受为期10周的安慰剂或固定剂量奥氮平（1.0、2.5、5.0、7.5毫克/天）双盲治疗。
平均年龄为76.6±10.4岁。重复测量分析显示，所有五个治疗组的NPI/NH精神病总分（妄想、幻觉项目总和 - 主要疗效指标）相对于基线均有显著改善（p<0.001），但在10周终点时未观察到两两治疗组之间的差异。然而，根据末次观察结转（LOCF）分析，7.5毫克奥氮平组的改善程度（-6.2±4.9）显著大于安慰剂组（-5.0±6.1，p = 0.008），而终点时CGI - C评分显示，奥氮平2.5毫克组相对于安慰剂组（3.2±1.4）改善最大（2.8±1.4，p = 0.030）。在体重增加、厌食和尿失禁方面，各治疗组总体存在显著差异，奥氮平组的发生率在数值上更高。然而，相对于安慰剂，任何奥氮平组中包括锥体外系症状在内的任何其他个体事件的发生率以及总不良事件的发生率均未显著更高。各治疗组在认知或任何其他生命体征或实验室指标（包括血糖、甘油三酯和胆固醇）方面均未观察到具有临床意义的显著变化。
虽然1.0毫克奥氮平与安慰剂相比未显示出显著差异，但2.5毫克剂量是一个合理的起始剂量。每天7.5毫克的奥氮平显著降低了精神病性症状和总体行为障碍（NPI/NH，BPRS），且耐受性良好。
