Department of Neurology, University of Chicago Medicine and Biological Sciences, Chicago, IL, United States.
Department of Neurology, University of Chicago Medicine and Biological Sciences, Chicago, IL, United States.
Clin Neurol Neurosurg. 2020 Jul;194:105815. doi: 10.1016/j.clineuro.2020.105815. Epub 2020 Mar 21.
We conducted an updated systematic review on the safety and efficacy of amantadine in cognitive recovery after traumatic brain injury (TBI), in order to determine if the current literature justifies its use in this clinical condition. A comprehensive search strategy was applied to three databases (PubMed, Scopus, and Cochrane). Only randomized clinical trials (RCTs) that compared the effect of amantadine and placebo in adults within 3 months of TBI were included in the review. Study characteristics, outcomes, and methodological quality were synthesized. This systematic review was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A quantitative synthesis (meta-analysis) was not feasible due to the large heterogeneity of studies identified. Three parallel RCTs and one cross-over RCT, with a total of 325 patients were included. All of the studies evaluated only severe TBI in adults. Amantadine was found to be well tolerated across the studies. Two RCTs reported improvement in the intermediate-term cognitive recovery (four to six weeks after end of treatment), using DRS (in both studies) and MMSE, GOS, and FIM-Cog (in one study). The effect of amantadine on the short-term (seven days to discharge) and long-term (six months from the injury) cognitive outcome was found not superior to placebo in two RCTs. The rate of severe adverse events was found to be consistently very low across the studies (the incidence of seizures, elevation in liver enzymes and cardiac death was 0.7 %, 1.9 %, and 0.3 %, respectively). In conclusion, amantadine seems to be well tolerated and might hasten the rate of cognitive recovery in the intermediate-term outcome. However, the long-term effect of amantadine in cognitive recovery is not well defined and further large randomized clinical trials in refined subgroups of patients are needed to better define its application.
我们对金刚烷胺在创伤性脑损伤（TBI）后认知恢复中的安全性和有效性进行了更新的系统评价，以确定当前的文献是否证明其在这种临床情况下的使用是合理的。我们应用了全面的检索策略来检索三个数据库（PubMed、Scopus 和 Cochrane）。只有将金刚烷胺与安慰剂在 TBI 后 3 个月内进行比较的成人随机临床试验（RCT）才被纳入综述。我们综合了研究特征、结局和方法学质量。这项系统评价是按照系统评价和荟萃分析的首选报告项目（PRISMA）进行和呈现的。由于确定的研究存在很大的异质性，因此无法进行定量综合（荟萃分析）。共有三项平行 RCT 和一项交叉 RCT，共纳入 325 名患者。所有研究均仅评估了成人严重 TBI。金刚烷胺在各项研究中均具有良好的耐受性。两项 RCT 报告了在中期认知恢复（治疗结束后 4 至 6 周）中使用 DRS（两项研究）和 MMSE、GOS 和 FIM-Cog（一项研究）的改善。在两项 RCT 中，发现金刚烷胺对短期（7 天至出院）和长期（损伤后 6 个月）认知结局的影响并不优于安慰剂。在所有研究中，严重不良事件的发生率均保持非常低（癫痫发作、肝酶升高和心脏死亡的发生率分别为 0.7%、1.9%和 0.3%）。总之，金刚烷胺似乎具有良好的耐受性，并且可能加速中期认知恢复的速度。然而，金刚烷胺在认知恢复中的长期效果尚未明确，需要进一步进行针对患者亚组的大型随机临床试验，以更好地确定其应用。
