Evaluation of the impact of memantine treatment initiation on psychotropic drug use (Vidal et al, 2008)56
This study utilised the French national healthcare database to test the hypothesis that the initiation of memantine treatment could modify the consumption of psychotropic drugs in real-life clinical practice patients.
A sample of patients treated in the general population, extracted from the database of the French national healthcare system (CNAM-TS), was examined in this 2-year follow-up cohort study. The CNAM-TS database includes drug consumption data. The sample included 4,600 memantine-treated patients (aged ≥65 years) randomly selected from the database. An interrupted time series analysis of the proportion of psychotropic drug users and speci?c categories – before and after the onset of memantine treatment – was performed.
Before the initiation of memantine treatment, there had been a regular increase of 39–50% in patients treated with psychotropic drugs. This trend for increased psychotropic drug usage stopped when memantine treatment was initiated, with the proportion of psychotropic drug users remaining stable at ~53% up to the end of the analysis period. This difference in the trends before and after memantine treatment initiation was signi?cant (p<0.001).
The same pattern was observed for all sub-categories of psychotropic drugs analysed (antidepressants, neuroleptics, anxiolytics, hypnotics; all p≤0.001).
The results suggest that there is a temporal relationship between the onset of memantine treatment and the stabilisation of psychotropic drug usage.
In addition to its overall bene?ts on cognition, function and behaviour, memantine produced signi?cant bene?ts in moderate to severe AD, including speci?c single items of:
cognition – construction, language, praxis, memory, orientation, visuospatial ability
function – conversing, grooming, watching TV, ?nding belongings, toileting
behaviour – agitation/aggression, irritability/lability, delusions, and night-time behaviour.
Memantine signi?cantly prevented the emergence of behavioural symptoms such as agitation/aggression, irritability/lability, and night-time behaviour.
In behaviourally disturbed patients, memantine had signi?cant effects in reducing agitation/aggression and psychotic symptoms as well as signi?cantly bene?ting cognitive, functional and global outcomes in these patients.
Withdrawal of memantine treatment in nursing home residents with AD can lead to an increase in the use of psychotropic drugs and to weight loss.
Long-term data
Long-term extension of MD-01 and MD-02 (Tariot et al, 2006)57
MD-01 and MD-02 were utilised as lead-in studies for a 134-week extension study which evaluated the long-term safety and ef?cacy of memantine in patients with moderate to severe AD, as well as the tolerability of a shorter titration period and once-daily dosing.
This study recruited patients with moderate to severe AD who had participated in either of two 24-week, double-blind, placebo-controlled lead-in clinical studies (MEM-MD-01 and MEM-MD-02, see Table 6.1). The extension study consisted of a 4-week, double-blind titration period, followed by open-label maintenance periods of 24 weeks, 52 weeks, and 54 weeks.
During the titration period, patients who had been previously treated with memantine in the lead-in studies were maintained on 10 mg twice-daily, or were switched to 20 mg once-daily, dosing. Patients who had previously received placebo were randomised to one of four groups in order to investigate two titration schemes (22-day vs 8-day) and two dosing schemes (10 mg twice-daily vs 20 mg once-daily). At the end of the 4-week titration period, patients received memantine treatment (10 mg twice-daily) for a total of 130 weeks.
The SIB and CIBIC-Plus were used to assess long-term ef?cacy, compared to projected placebo declines.
Results
Compared to the projected rate of decline for untreated patients, long-term memantine treatment was associated with signi?cantly lower rates of decline on the SIB (Figure 6.18a) and CIBIC-Plus (Figure 6.18b) at one, two and three years after the baseline assessment.
Analysis of titration protocols revealed that once- vs twice-daily dosing during titration resulted in no marked differences, although 8-day titration may lead to higher instances of dizziness and fatigue than the standard 22-day titration.
AEs were similar in type and frequency between groups, were predominantly mild to moderate in severity, and judged unrelated to memantine; the most common AEs were agitation, fall, accidental injury, and urinary tract infection.
This study supported the long-term ef?cacy and safety of memantine in the treatment of moderate to severe AD.
We translated the file about Evaluation of the impact of memantine treatment initiation on psychotropic drug use from English into Chinese.
评价美金刚治疗对使用精神治疗药物的影响（Vidal 等， 2008）56
该研究利用法国国家医疗保健数据库评价美金刚治疗能否影响现实生活中临床实践患者精神治疗药物的使用
从法国国家医疗保健系统（CNAM-TS）中抽取具有代表性的患者，对其进行2年随访的队列研究。CNAM-TS数据库包括药物使用数据。该样本包括随进从数据库中抽取的4,600名美金刚治疗患者（年龄≥65岁）。在服用美金刚之前及服用美金刚之后，进行服用精神治疗药物患者比例及药物种类的中断时间序列分析。
在服用美金刚之前，使用精神药物治疗的患者的比例固定增加39-50%。当开始使用美金刚治疗时，使用精神药物治疗的患者比例升高的倾向即发生停止。使用精神药物治疗的患者比例稳定维持在53%左右，直至分析结束。在服用美金刚之前及之后，服用精神药物治疗倾向的变化具有显著统计学意义（p<0.001）。
对各类精神治疗药物（抗抑郁药、精神安定药、抗焦虑药、安眠药；p值均≤0.001）的分析发现服用美金刚前后也存在相同的模式。
这些结果表明，服用美金刚治疗与稳定使用精神治疗药物之间存在暂时的相关关系。
除了在认知能力、功能及行为等总的方面受益外，美金刚对中、重度AD患者的明显受益包括以下特异性单项：
认知能力 ― 构建、语言、实践、记忆、定位、视觉空间能力
功能 ― 交谈、梳理、看电视、寻找随身物品、上厕所
行为 ― 焦虑/攻击、易怒/情绪不稳定、妄想、及夜间行为
美金刚可以明显防止行为症状的出现，例如焦虑/攻击、易怒/情绪不稳定及夜间行为
对行为障碍的患者，美金刚可以显著减少患者焦虑/攻击及精神症状，以及可以使患者在认知能力、功能及整体状况方面明显受益。
在护理院退出美金刚治疗的AD患者可导致精神治疗药物的使用增加及体重减轻。
长期数据
MD-01 及 MD-02的长期扩展研究(Tariot 等，2006)57
MD-01及MD-02被作为一个134周扩展研究的导入研究，在这个为期134周的扩展研究中，评价了美金刚治疗中、重度AD患者的长期安全性及有效性，以及缩短滴定期及一天一次剂量的耐受性。
该研究所招募的中、重度AD受试者已经参加了两个中任一一个24周、双盲、安慰剂对照的、导入临床研究（MEM-MD-01 及 MEM-MD-02，见表 6.1）。扩展研究包括一个4周、双盲的滴定期，随后为开放的24周、52周及54周维持期，
在滴定期期间，之前在导入期已经接受美金刚治疗的患者维持服用一天两次，一次10mg剂量的美金刚，或者改为服用一天一次，一次20mg剂量的美金刚。
为了对两个滴定方案（22天或者8天）及两个给药剂量方案（10mg一次，一天两次及20mg一次，一天一次）进行研究，之前接受安慰剂治疗的患者被随机进入4组中的一组。在4周的滴定期结束后，受试者接受130周的美金刚治疗（10mg一次，一天两次）。
与估计的安慰剂组恶化情况进行比较，采用SIB及CIBIC-Plus评价美金刚的长期有效性。
结果
与安慰剂组估计的恶化率比较，长期接受美金刚治疗在基线评估后的一年、两年及三年可以极大地降低SIB恶化率（图6.18a）及CIBIC-Plus恶化率（图6.18b）。
滴定方案分析表明在滴定期间一天一次给药及一天两次给药之间无明显差异，与标准的22天滴定期比较，8天的滴定期可导致更高比例的眩晕及疲乏。
组与组之间不良事件发生的类型及频率相似，大部分为轻、重度不良事件，并且与美金刚无关；最常见的不良事件为焦虑、跌倒、以外受伤及尿道感染。
该研究证实了美金刚治疗中、重度AD患者的长期有效性及安全性。 原件下载： 
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