Previous research indicates that AD patients with agitation/aggression and psychotic features deteriorate more rapidly.^47-50 However, there are concerns over the safe use of atypical antipsychotic agents in patients with dementia.^51-53

A pooled analysis was performed on memantine studies in moderate to severe AD (MRZ-9605, MD-01, MD-02) to assess the specifc effects of memantine in behaviourally disturbed patients – that is, in patients with ‘agitation/aggression’ and ‘psychosis’ at baseline.⁵⁴ The Behaviourally Disturbed Population (BDP), comprised patients scoring >0 on any of three NPI items – ‘delusions’, ‘hallucinations’, and/or ‘agitation/aggression’ – at baseline.

        Memantine signifcantly improved the NPI sub-item cluster of ‘agitation and psychosis’ (combined score of the ‘delusions’, ‘hallucinations’, and ‘agitation/aggression’ items) versus placebo deterioration at both Week 12 (-0.8 points vs 0.5 points; p<0.01) and Week 24/28 (-0.7 points vs 0.7 points; p<0.001).⁵⁴

       There were signifcantly more responders (improvement in NPI cluster score from baseline) in the memantine group than in the placebo group at Week 12 (55% vs 43%; p<0.05), and Week 24/28 (61% vs 45%; p<0.01) (Figure 6.15).⁵⁴

        In the subgroup of patients without the NPI sub-item cluster of ‘agitation and psychosis’ at baseline (i.e., non-BDP, asymptomatic), memantine prevented the emergence of these symptoms, with signifcantly fewer patients developing the symptoms at Week 12 (20% vs 32%; p=0.01) and at Week 24/28 (24% vs 37%; p<0.01), as compared with placebo.⁵⁴

 

Global, cognitive, functional and behavioural domains

        Memantine produced a signifcant beneft over placebo for all four main outcome measures: total scores for SIB, CIBIC-Plus, ADCS-ADL_sev (Figure 6.16), OC and LOCF analyses.⁵⁴

        The treatment effects were larger in the BDP patients, compared with the total population, mostly due to a larger decline in the BDP placebo group (Figure 6.16).³¹

        At study endpoint (Week 24/28, LOCF), approximately half of the memantine-treated BDP patients were either stabilised or improved relative to baseline across these three measures.⁵⁴

 

Data from medical charts of subjects aged ≥50 years, and living in nursing homes for ≥90 days were collected from nursing homes in the US. Comparisons were made between two groups (n=521):

        residents who took memantine continuously for ≥90 days (n=273)

        residents who took memantine for ≥30 days and then discontinued for ≥60 days (n=248).

        As shown in Figure 6.17, compared with nursing home residents who were continuously maintained on memantine, discontinuation of memantine for ≥60 days was associated with signifcantly higher odds of increased use of:

       psychotropic drugs (32.3% vs 16.5%; OR=2.29; p<0.001)

       anticonvulsants (OR=5.95; p=0.005)

       antidepressants (OR=3.21; p<0.001)

       antipsychotics (OR=2.27; p=0.012)

       anxiolytics (OR=2.53; p=0.01).

        The effect was not signifcant for sedatives/hypnotics (OR=1.45; p=0.60).

        Residents who discontinued memantine experienced adjusted mean (± SEM) weight loss of 1.20 ± 0.32 kg (p<0.001) compared to a weight gain of 0.34 ± 0.29 kg in those who took memantine continuously.

The study concluded that in comparing continuous administration and discontinuation of memantine in nursing home residents with AD, discontinuation of memantine therapy was associated with higher odds of increased psychotropic drug use (including anticonvulsants, antidepressants, antipsychotics, and anxiolytics) and with signifcant weight loss.

 

Beijing Chinese Translation Service Company has translated many documents about Benefts in behaviourally disturbed patients.

 

前面的研究表明：具有焦虑/攻击及精神症状特征的AD患者病情恶化更加快速^47-50。然而，对痴呆患者使用非典型抗精神病药物具有安全性方面的担心^51-53。

汇总三项（MRZ-9605、 MD-01、 MD-02）关于美金刚治疗中、重度AD患者研究的数据，评价美金刚治疗行为障碍患者（即在基线具有“焦虑/攻击”及“精神病症状”的患者）的特异性效应⁵⁴。行为障碍人群包括在在基线三项NPI细项（“妄想”、“幻觉”和/或“焦虑/攻击”）中任一一项评分大于“0”的患者。

         与安慰剂组相比，在第12周及第24/28周时，美金刚极大地改善NPI细项“焦虑及精神症状”（即“妄想”、“幻觉”及“焦虑/攻击”项的联合评分）组合评分，第12周时（美金刚组：-0.8分，安慰剂组：0.5分；p<0.01），第24/28周时（美金刚组：-0.7分，安慰剂组：0.7分；p<0.001）⁵⁴。

         在第12周及第24/28周时，美金刚组有效应答的患者比例（改善NPI组合评分）明显高于安慰剂组，第12周时（美金刚组组：55%，安慰剂：43%；p<0.05），第24/28周时（美金刚组：61%，安慰剂：45%；p<0.01）（图6.15）⁵⁴。

         在基线无NPI次级量表组合“焦虑及精神症状”的患者亚组（也就是说非行为障碍患者，无症状），美金刚可以防止这些症状的出现，在第12周、24/28周，美金刚组出现这些症状的患者明显低于与安慰剂组，第12周（美金刚组：20%，安慰剂组：32%；p=0.01），第24/28周（美金刚组：24%，安慰剂组：37%；p<0.01）⁵⁴。

 

         与安慰剂组相比，美金刚能给患者在四个主要结果评价方面带来明显受益：SIB总分、CIBIC-Plus、ADCS-ADL_sev（图6.16），OC分析及LOCF分析⁵⁴。

         与总患者人群相比，BDP患者的治疗效用更大，主要是因为在BDP安慰剂组患者的病情恶化更加迅速（图6.16）。³¹

         在研究终点（24//28周，LOCF），大约一半的美金刚治疗的BDP患者在这三项评价指标方面病情稳定，或者较基线出现改善。⁵⁴

 

中断美金刚治疗对精神药物使用及体重的影响（Fillit 等， 2008）⁵⁵

从美国护理院的病历中收集数据的受试者年龄≥50岁，在护理院的生活时间≥90天。对以下两个组之间的患者进行比较（n=521）：

         连续服用美金刚≥90天的患者（n=273）

         连续服用美金刚≥30天、并且中断服用美金刚≥60天的患者（n=248）

         如6.17所示，在护理院连续服用美金刚的患者与中断美金刚治疗≥60天的患者进行比较发现，中断美金刚治疗的患者组使用以下药物的比例更高：

      精神治疗药物（中断美金刚治疗组：32.3%，连续服用美金刚组16.5%；OR（比值比）=2.29；p<0.001）

       抗惊厥药（OR（比值比）=5.95；p=0.005）

       抗抑郁药（OR（比值比）=3.21；p<0.001）

       抗精神病药（OR（比值比）=2.27； p=0.012）

       抗焦虑剂（OR（比值比）=2.53； p=0.01）

         使用镇静剂/安眠药的效用不明显（OR（比值比）=1.45；p=0.60）。

         中断美金刚治疗的患者校正平均（±SEM）体重减轻1.20 ± 0.32 kg，而连续服用美金刚的患者平均体重增加0.34 ± 0.29 kg（p<0.001）。 

 该研究得出结论:对护理院连续服用美金刚的AD患者与中断美金刚治疗的AD患者进行比较发现，中断美金刚治疗导致患者服用精神治疗药物（包括抗惊厥药、抗抑郁药、抗精神病药及抗焦虑药）的比例增加，并且导致明显的体重减轻。

 

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