Importance:

Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear.

Objective:

To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy.

Methods:

The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020.

Results:

Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on Gingko biloba in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research.

Conclusion:

Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.

中文翻译：

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阿尔茨海默病：单一疗法和联合疗法的疗效。系统回顾

 重要性：

阿尔茨海默病 (AD) 是一种复杂的神经退行性疾病，也是痴呆症最常见的原因。尽管迫切需要更有效的 AD 药物治疗策略，但与现有药物联合治疗的疗效证据仍不清楚。

 客观的：

与单药药物治疗相比，评估联合药物治疗对 AD 患者认知和进展的疗效。

 方法：

系统地检索了电子数据库 MEDLINE 和 EMBASE，以确定相关出版物。仅纳入随机对照临床试验，但对发表的语言或时间没有限制。数据提取时间为2020年5月27日至12月29日。

 结果：

三项试验发现，与 ChEI 单一疗法和安慰剂相比，ChEI 与额外美金刚的组合为中度至重度 AD 患者提供了轻微的益处。然而，另外 4 项试验未能复制这种效果。一项试验报告了与多奈哌齐加安慰剂相比，附加银杏叶对接受多奈哌齐治疗的中度 AD 患者（使用含有银杏和其他抗氧化剂的配方）的益处。进一步的试验发现，与多奈哌齐加安慰剂相比，EGb 761® 和多奈哌齐联合治疗可能患有 AD 的患者没有显着效果。伊达洛吡啶、阿托伐他汀或维生素补充剂与 ChEI 联合使用的方法尚未被证明有效，此后也没有再尝试过。氟西汀和 ST101 与 ChEI 联合使用优于 ChEI 单一疗法和安慰剂。然而，这些效应必须通过进一步的研究来复制。

 结论：

额外的美金刚联合 ChEI 可能对中度至重度 AD 患者有轻微益处，但证据尚不明确。需要更长时间的试验。如果仅开始适当的 ChEI 单一疗法，就不会错过任何主要的认知益处。