van der Veen Ruud, Königs Marsh, Bakker Simon, van Iperen Andries, Peerdeman Saskia, Bet Pierre M, Oosterlaan Jaap
Follow Me Program & Emma Neuroscience Group, Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.
Daan Theeuwes Center for Intensive Neurorehabilitation, Woerden, The Netherlands.
Clin Pharmacol Ther. 2024 May;115(5):971-987. doi: 10.1002/cpt.3186. Epub 2024 Jan 31.
Cognitive impairments, common sequelae of acquired brain injury (ABI), significantly affect rehabilitation and quality of life. Currently, there is no solid evidence-base for pharmacotherapy to improve cognitive functioning after ABI, nevertheless off-label use is widely applied in clinical practice. This meta-analysis and meta-regression aims to quantitatively aggregate the available evidence for the effects of pharmacological agents used in the treatment of cognitive impairments following ABI. We conducted a comprehensive search of Embase, Medline Ovid, and Cochrane Controlled Trials Register databases for randomized controlled and crossover trials. Meta-analytic effects were calculated for each pharmaceutical agent and targeted neuromodulator system. Cognitive outcome measures were aggregated across cognitive domains. Of 8,216 articles, 41 studies (4,434 patients) were included. The noradrenergic agent methylphenidate showed a small, significant positive effect on cognitive functioning in patients with traumatic brain injury (TBI; k = 14, d = 0.34, 95% confidence interval: 0.12-0.56, P = 0.003). Specifically, methylphenidate was found to improve cognitive functions related to executive memory, baseline speed, inhibitory control, and variability in responding. The cholinergic drug donepezil demonstrated a large effect size, albeit based on a limited number of studies (k = 3, d = 1.68, P = 0.03). No significant effects were observed for other agents. Additionally, meta-regression analysis did not identify significant sources of heterogeneity in treatment response. Our meta-analysis supports the use of methylphenidate for enhancing cognitive functioning in patients with TBI. Although donepezil shows potential, it warrants further research. These results could guide clinical decision making, inform practice guidelines, and direct future pharmacotherapeutic research in ABI.
认知障碍是获得性脑损伤（ABI）的常见后遗症，会显著影响康复和生活质量。目前，尚无确凿的循证依据支持药物疗法可改善ABI后的认知功能，不过，超说明书用药在临床实践中却被广泛应用。本荟萃分析和荟萃回归旨在定量汇总有关用于治疗ABI后认知障碍的药物疗效的现有证据。我们全面检索了Embase、Medline Ovid和Cochrane对照试验注册数据库，以查找随机对照试验和交叉试验。针对每种药物和靶向神经调节系统计算荟萃分析效应。跨认知领域汇总认知结果测量指标。在8216篇文章中，纳入了41项研究（4434例患者）。去甲肾上腺素能药物哌甲酯对创伤性脑损伤（TBI）患者的认知功能显示出小而显著的积极作用（k = 14，d = 0.34，95%置信区间：0.12 - 0.56，P = 0.003）。具体而言，发现哌甲酯可改善与执行记忆、基线速度、抑制控制和反应变异性相关的认知功能。胆碱能药物多奈哌齐显示出较大的效应量，尽管基于的研究数量有限（k = 3，d = 1.68，P = 0.03）。未观察到其他药物有显著效果。此外，荟萃回归分析未发现治疗反应中存在显著的异质性来源。我们的荟萃分析支持使用哌甲酯增强TBI患者的认知功能。尽管多奈哌齐显示出潜力，但仍需进一步研究。这些结果可为临床决策提供指导，为实践指南提供信息，并指导未来ABI的药物治疗研究。
