Objective To evaluate the effectiveness and safety of donepezil in the treatment of senile vascular dementia. Methods The databases such as the Chinese Journal Full-text Database, Chinese Biomedical Literature Database, Chinese Scientific Journals Full-text Database, Chinese Biomedicine Database, PubMed and The Cochrane Library were searched by computer, and the related journals and conference proceedings were also manually searched to include randomized controlled trials (RCTs) on donepezil in the treatment of senile vascular dementia. Studies were screened according to the inclusion and exclusion criteria, data were extracted, the methodological quality of the included studies was assessed according to Jadad score criterion, and meta-analyses were performed by using RevMan 5.0 software. Results Among 25 studies (3586 patients) included, eight described the randomization methods, and three described the double blind methods. The results of meta-analyses showed, compared with the placebo group, donepezil was superior in improving vascular dementia patients’ cognition level (three studies, MD= –1.25, 95%CI –1.61 to –0.88, Plt;0.000 01), intellectual spirit level (two studies, MD=0.66, 95%CI 0.35 to 0.97, Plt;0.000 1), dementia level (three studies, MD= –0.74, 95%CI –1.16 to –0.31, P=0.004), and viability level (two studies, MD= –0.74, 95%CI –1.16 to –0.31, P=0.000 6). In improving the intellectual spirit level, donepezil was superior to piracetam (seven studies, MD=3.25, 95%CI 2.15 to 4.35, Plt;0.000 01), Xuesaitong (two studies, MD=6.12, 95%CI 4.02 to 8.22), Huperzine A (three studies, MD=2.45, 95%CI 1.14 to 3.76, P=0.000 2), and vitamin (two studies, MD=4.00, 95%CI 2.73 to 5.27, Plt;0.000 01). For improving the viability level, donepezil was superior to piracetam (five studies, MD= –3.86, 95%CI –4.83 to –2.89, Plt;0.000 01), Xuesaitong (two studies, MD= –5.49, 95%CI –7.18 to –3.80, Plt;0.000 01), Huperzine A (two studies, MD= –0.78, 95%CI –4.23 to –2.66, P=0.66), vitamin (three studies, MD= –5.88, 95%CI –8.29 to –3.48, Plt;0.000 01), and nimodipine (one study, MD= –7.09, 95%CI –10.81 to –3.37, P=0.000 2). In improving the dementia level (HDS Scale), donepezil was superior to piracetam (one study, MD=5.80, 95%CI 2.78 to 8.82, P=0.000 2), Xuesaitong (one study, MD=3.95, 95%CI 2.32 to 5.58, Plt;0.000 01), vitamin (one study, MD=3.91, 95%CI 0.94 to 6.88, P=0.010), and almitrine (one study, MD=3.37, 95%CI 1.10 to 5.64, P=0.004). Conclusion Current evidence shows that donepezil is likely to be more effective in the treatment of vascular dementia than placebo, piracetam, Xuesaitong, Huperzine A and vitamin. However, for the limited evidence and lower methodological quality of the included studies, this conclusion still needs to be verified with more high-quality RCTs.
Controversy exists regarding the ethics of using placebo control groups in clinical trials when effective treatments exist. The debate was fueled by the announcement of the 5th revision of the Declaration of Helsinki (2000). This study reviews the history and scientific background surrounding the controversy and investigates the prevailing attitudes of Hong Kong researchers regarding this issue. The controversy has centered on a few issues. The first involves the methodological superiority of placebo-controlled trials in discerning treatment effects. Secondly, it is unclear if the treatment effects encompass absolute treatment effects (including placebo effects) or are confined to treatment-specific effects (excluding placebo effects). Thirdly, there are worries that subjects in the placebo group could be exposed to higher risk for developing serious adverse events. Fourthly, it is debated whether the standard of best available treatment should be a local one, or an international one. Preliminary research findings suggest that the opinions of the Hong Kong researchers seemed to be divided on the use of placebo control groups in clinical trials when effective treatment exists. Further researcher on the topic is therefore warranted, training and consensus meeting may be necessary to minimize the confusion related to this issue.