Meta-Analysis of Randomized Controlled Trials on the Efficacy and Safety of Donepezil, Galantamine, Rivastigmine, and Memantine for the Treatment of Alzheimer’s Disease

Abstract

To study the impact of donepezil, rivastigmine, galantamine, and memantine on cognitive, functional, behavioral, global changes and adverse effects in patients with mild, moderate and severe Alzheimer’s disease (AD), we screened the literature published before September 2017 in the Pubmed, Embase, Cochrane library and Web of Science Electronic databases according to the inclusion criteria. Thirty-six studies were finally determined from 1560 preliminary screened articles. The AD Assessment Scale-cognitive Subscale (ADAS-cog), AD Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), and Clinician’s Interview-Based Impression of Change Plus Caregiver Input scale (CIBIC+) were used as valid endpoints. Of the 36 trials included, meta-analyses of these placebo-control trials showed that there were significant differences between the donepezil, rivastigmine and placebo groups using ADAS-cog, ADCS-ADL, and CIBIC+. Meta-analyses of these placebo-controlled trials showed that there were significant differences between the galantamine and placebo groups using ADAS-cog, ADCS-ADL, NPI, and CIBIC+. These observations suggest that memantine is beneficial for stabilizing or slowing the decline in ADAS-cog and ADCS-ADL 19 changes in AD patients. However, there was no significant effect according to the ADCS-ADL 23 , NPI, and CIBIC+ tests, which indicated that memantine treatment has no significant effect on these cognitive aspects of AD patients. Different effects of donepezil, rivastigmine, galantamine, or memantine on AD were found in this study. According to the results, we conclude that galantamine is effective in treating all aspects of AD and is the first choice for the treatment of AD. However, due to limited data, we should consider additional data to obtain more stable results.

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

“…Tacrine was introduced in 1993 and discontinued years later due to hepatoxicity; Donepezil was introduced in 1996; Galantamine was introduced in 2001; and Rivastigmine was introduced in 2002. Memantine, an NMDA partial antagonist, was approved by the FDA in 2003 [104,105]. Over the past decade, the most prevalent pharmacological categories currently investigated as candidate strategies for the treatment of AD included neurotransmitter enhancers (11.38%), anti-Amyloid agents (13.30%), multi-target drugs (2.45%), anti-Tau agents (2.03%), and diverse natural products (25.58%).…”

DL-3-n-butylphthalide Delays Cognitive Decline in Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil: A Multicenter, Prospective Cohort Study

“…Currently, AD is still mainly treated with cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, which can only delay the progression of the disease [22][23][24][25][26]. All treatments targeting the pathological changes of AD are still in the testing phase [27][28][29][30].…”

Response to Placebo in Fragile X Syndrome Clinical Trials: An Initial Analysis

“…For those efficacy endpoints showing significant heterogeneity (I 2 p ≤ 0.05), random effects meta-analyses were carried out. Other aspects of the meta-analyses’ procedure have been previously reported [ 16 , 35 ].…”

“…To determine the functional or clinical significance of the improvements in placebo groups, the effect size of delta scores was calculated as a function of SDs at baseline. In addition, for performance-rated outcome measures, we compared differences between baseline and EOT scores with expected developmental changes (either monthly or annually) for the endpoint as estimated by natural history studies (e.g., Vineland-II [ 35 ]). For measures with psychometric reference data (e.g., ABC-CFX [ 33 ]), we compared the delta scores with the SD/mean ratio for individuals in a specific age range.…”

“…Overall, the development of valid, sensitive-to-treatment biomarkers is necessary to reliably track treatment changes in the unfolding wave of clinical trials in FXS [ 8 , 52 ], which will substantially reduce the placebo effect. The examination of factors contributing to responses in placebo groups should be a continuous process [ 35 , 53 ] parallel to efforts at improving the measurement properties of endpoints in drug trials, including performance-rated measures [ 9 ].…”