From the Department of Clinical Pharmacy and Pharmacy Practice (M.S.M.), Faculty of Pharmacy, Pharos University in Alexandria; and Department of Biomedical Informatics and Medical Statistics (I.E.S., A.Z.), Medical Research Institute, and Department of Critical Care Medicine (S.A.), Faculty of Medicine, Alexandria University, Alexandria, Egypt.
J Trauma Acute Care Surg. 2022 Mar 1;92(3):605-614. doi: 10.1097/TA.0000000000003363.
Traumatic brain injury is a global burden. We aimed to perform a meta-analysis to determine the efficacy of amantadine for cognitive performance after traumatic brain injury.
The systematic review was prospectively registered on the International Prospective Register of Systematic Reviews website under the registration number CRD42017080044. We used Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to report the steps of meta-analysis. The search included electronic databases (PubMed, PsycINFO, Embase, Cochrane Library databases, CENTRAL, ProQuest and ClinicalTrials.gov trial registry). Critical care medicine journals and clinical neurology specialty were searched using www.scimagojr.com. There was no publication date restriction. Two authors assessed studies' relevance and extracted data. Studies were assessed for quality using the Cochrane risk of bias tool. Data were analyzed using Comprehensive Meta-analysis Program versions 2.0 and 3.0.
Twenty-six studies out of 3,440 records were included in the systematic review, of which only 14 clinical trials and 6 observational studies were included in the meta-analysis. Amantadine significantly enhanced the cognitive function relative to control group (mean difference [MD], 0.50; 95% confidence interval [CI], 0.33-0.66; p < 0.001, 16 studies, 1,127 participants, low certainty evidence). Consistent significant difference in favor of amantadine relative to control group was found (MD of 0.79 [95% CI, 0.34-1.24], very low certainty evidence, for cohort studies vs. MD of 0.40 [95% CI, 0.25-0.56], moderate certainty evidence, for RCTS). Starting amantadine in the first week after TBI had a significant effect on improving cognitive function (MD, 0.97; 95% CI, 0.45-1.49; 16 studies, 1,127 participants, low certainty). Amantadine showed a better effect when administered for less than 1 month (MD, 0.83; 95% CI, 0.56-1.11; low certainty) and to patients below 18 years of age (MD, 0.66; 95% CI, 0.32-0.99; low certainty) or to patients with less severe traumatic brain injury (MD, 0.40; 95% CI, 0.18-0.62; low certainty). No statistically significant difference existed between amantadine and the control concerning the adverse events (OR, 1.74; 95% CI, 0.88-3.44; p = 0.11, moderate certainty). Metaregression of the different clinical parameters, which are onset of treatment, age, and severity of traumatic brain injury, showed a statistically significant relation between onset of treatment and the effect size of amantadine. The relation between the other two parameters and the effect size of amantadine showed a marginal statistical significance.
Amantadine may improve the cognitive function when used after TBI. Further research with high validity is needed to reach a solid conclusion about the use of amantadine in traumatic brain injury.
Systematic review/meta-analysis, level III.
创伤性脑损伤是一个全球性的负担。我们旨在进行荟萃分析，以确定金刚烷胺对创伤性脑损伤后认知表现的疗效。
系统评价前瞻性地在国际系统评价注册中心网站上注册，注册编号为 CRD42017080044。我们使用系统评价和荟萃分析的首选报告项目指南来报告荟萃分析的步骤。检索包括电子数据库（PubMed、PsycINFO、Embase、Cochrane 图书馆数据库、CENTRAL、ProQuest 和 ClinicalTrials.gov 试验注册处）。使用 www.scimagojr.com 搜索了重症监护医学杂志和临床神经病学专业。没有发布日期限制。两名作者评估了研究的相关性并提取了数据。使用 Cochrane 偏倚风险工具评估了研究的质量。使用 Comprehensive Meta-analysis Program 版本 2.0 和 3.0 分析数据。
在 3440 条记录中，有 26 项研究被纳入系统评价，其中只有 14 项临床试验和 6 项观察性研究被纳入荟萃分析。与对照组相比，金刚烷胺显著增强了认知功能（平均差异[MD]，0.50；95%置信区间[CI]，0.33-0.66；p<0.001，16 项研究，1127 名参与者，低确定性证据）。与对照组相比，金刚烷胺的显著差异也得到了一致的支持（队列研究的 MD 为 0.79 [95% CI，0.34-1.24]，极低确定性证据，与 RCTS 的 MD 为 0.40 [95% CI，0.25-0.56]，中等确定性证据）。在创伤性脑损伤后第一周开始使用金刚烷胺对改善认知功能有显著效果（MD，0.97；95% CI，0.45-1.49；16 项研究，1127 名参与者，低确定性）。金刚烷胺的效果更好当治疗时间少于 1 个月时（MD，0.83；95% CI，0.56-1.11；低确定性）或治疗年龄小于 18 岁的患者（MD，0.66；95% CI，0.32-0.99；低确定性）或治疗创伤性脑损伤程度较轻的患者（MD，0.40；95% CI，0.18-0.62；低确定性）。金刚烷胺与对照组之间在不良事件方面没有统计学上的显著差异（OR，1.74；95% CI，0.88-3.44；p=0.11，中等确定性）。治疗开始时间、年龄和创伤性脑损伤严重程度等不同临床参数的元回归表明，治疗开始时间与金刚烷胺的效应大小之间存在统计学关系。其他两个参数与金刚烷胺的效应大小之间存在边缘统计学意义。
金刚烷胺可能改善创伤性脑损伤后的认知功能。需要进一步进行具有高有效性的研究，以得出关于金刚烷胺在创伤性脑损伤中应用的可靠结论。
系统评价/荟萃分析，III 级。
