Arciniegas David B, Almeida Emily J, Sander Angelle M, Bogaards Jay A, Giacino Joseph T, Hammond Flora M, Harrison-Felix Cynthia L, Hart Tessa, Ketchum Jessica M, Mellick David C, Sherer Mark, Whyte John, Zafonte Ross D
Behavioral Neurology Section, Department of Neurology, University of Colorado School of Medicine, Aurora (Arciniegas); Brain Injury Research Center, TIRR Memorial Hermann, Houston (Arciniegas, Sander, Sherer); H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston (Arciniegas, Sander, Bogaards, Sherer); Research Department, Craig Hospital, Englewood, Colo. (Almeida, Harrison-Felix, Ketchum, Mellick); Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, Mass. (Giacino, Zafonte); Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston (Giacino, Zafonte); Rehabilitation Hospital of Indiana, Indianapolis (Hammond); Department of Physical Medicine and Rehabilitation, Indiana University School of Medicine, Indianapolis (Hammond); Moss Rehabilitation Research Institute, Elkins Park, Pa. (Hart, Whyte); Department of Rehabilitation Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia (Hart).
J Neuropsychiatry Clin Neurosci. 2025 Spring;37(2):102-114. doi: 10.1176/appi.neuropsych.20230055. Epub 2024 Dec 4.
Memory impairments are common chronic and functionally important consequences of traumatic brain injury (TBI). Among patients with persistent verbal memory impairments due to TBI-related cholinergic deficits, donepezil (an acetylcholinesterase inhibitor) may improve these and related problems. The Multicenter Evaluation of Memory Remediation in TBI with Donepezil (MEMRI-TBI-D) study, a four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial, evaluated the efficacy of donepezil on verbal memory impairments, co-occurring cognitive and noncognitive neuropsychiatric problems, and functional status among persons with severe, persistent, and functionally limiting verbal memory problems at least 6 months after mild, moderate, or severe TBI. Efficacy, safety, and tolerability measures were assessed. Seventy-five participants were randomly assigned to donepezil (N=37) and placebo (N=38) groups. In both modified intent-to-treat and per-protocol analyses, donepezil significantly improved memory (i.e., verbal learning, as measured by the Hopkins Verbal Learning Test-Revised Total Trials 1-3, the primary outcome measure) when compared with placebo. Treatment-responder rates in the donepezil and placebo groups were 42% and 18%, respectively, yielding a number needed to treat of 3.5. Among donepezil responders, delayed recall and processing speed also improved significantly. Treatment-emergent adverse event rates for donepezil and placebo were 46% and 8%, respectively, and mild or moderate (85%); diarrhea and nausea were significantly more common in the donepezil group, yielding a number needed to harm of 6.25 and a likelihood to be helped or harmed ratio of 1.79. These results suggest that donepezil is an efficacious treatment for severe, persistent memory impairments after predominantly severe TBI, with a relatively favorable safety and tolerability profile.
记忆障碍是创伤性脑损伤（TBI）常见的慢性且具有功能重要性的后果。在因TBI相关胆碱能缺陷而存在持续性言语记忆障碍的患者中，多奈哌齐（一种乙酰胆碱酯酶抑制剂）可能改善这些及相关问题。多奈哌齐对TBI记忆修复的多中心评估（MEMRI-TBI-D）研究是一项四中心、随机、平行组、双盲、安慰剂对照的10周临床试验，评估了多奈哌齐对轻度、中度或重度TBI至少6个月后存在严重、持续性且功能受限的言语记忆问题患者的言语记忆障碍、同时出现的认知和非认知神经精神问题以及功能状态的疗效。评估了疗效、安全性和耐受性指标。75名参与者被随机分配到多奈哌齐组（N = 37）和安慰剂组（N = 38）。在改良意向性分析和符合方案分析中，与安慰剂相比，多奈哌齐均显著改善了记忆（即言语学习，通过霍普金斯言语学习测试修订版的总试验1 - 3测量，这是主要结局指标）。多奈哌齐组和安慰剂组的治疗反应率分别为42%和18%，治疗所需人数为3.5。在多奈哌齐反应者中，延迟回忆和处理速度也显著改善。多奈哌齐和安慰剂的治疗中出现的不良事件发生率分别为46%和8%，轻度或中度不良事件发生率为85%；腹泻和恶心在多奈哌齐组中显著更常见，伤害所需人数为6.25，受益与伤害的可能性比为1.79。这些结果表明，多奈哌齐是治疗主要为重度TBI后严重、持续性记忆障碍的有效疗法，具有相对良好的安全性和耐受性。
