Multicenter Evaluation of Memory Remediation in Traumatic Brain Injury With Donepezil: A Randomized Controlled Trial
Year: 2024
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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.
Source: Journal of Neuropsychiatry
Institutions: Memorial Hermann Institute for Rehabilitation and Research Foundation, Craig Hospital, Harvard University, Thomas Jefferson University, Baylor College of Medicine, Spaulding Rehabilitation Hospital, Moss Rehabilitation Hospital, Rehabilitation Hospital of Indiana, Indiana University School of Medicine, University of Colorado Anschutz, University of Colorado Denver
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4405011946