Amantadine Did Not Positively Impact Cognition in Chronic Traumatic Brain Injury: A Multi-Site, Randomized, Controlled Trial

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Despite limited evidence to support the use of amantadine to enhance cognitive function after traumatic brain injury (TBI), the clinical use for this purpose is highly prevalent and is often based on inferred belief systems. The aim of this study was to assess effect of amantadine on cognition among individuals with a history of TBI and behavioral disturbance using a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine 100 mg twice-daily versus placebo for 60 days. Included in the study were 119 individuals with two or more neuropsychological measures greater than 1 standard deviation below normative means from a larger study of 168 individuals with chronic TBI (>6 months post-injury) and irritability. Cognitive function was measured at treatment days 0, 28, and 60 with a battery of neuropsychological tests. Composite indices were generated: General Cognitive Index (included all measures), a Learning Memory Index (learning/memory measures), and Attention/Processing Speed Index (attention and executive function measures). Repeated-measures analysis of variance revealed statistically significant between-group differences favoring the placebo group at day 28 for General Cognitive Index ( p = 0.002) and Learning Memory Index ( p = 0.001), but not Attention/Processing Speed Index ( p = 0.25), whereas no statistically significant between-group differences were found at day 60. There were no statistically significant between-group differences on adverse events. Cognitive function in individuals with chronic TBI is not improved by amantadine 100 mg twice-daily. In the first 28 days of use, amantadine may impede cognitive processing. However, the effect size was small and mean scores for both groups were generally within expectations for persons with history of complicated mild-to-severe TBI, suggesting that changes observed across assessments may not have functional significance. The use of amantadine to enhance cognitive function is not supported by these findings.

Related collections

Most cited references 18

Record: found
Abstract: found
Article: not found

Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury

Joseph Giacino, John Whyte, Emilia Bagiella … (2012)

Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery. We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models. During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events. Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).

0 comments Cited 190 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Procedures for comparing samples with multiple endpoints.

Dennis P. O’Brien (1984)

Five procedures are considered for the comparison of two or more multivariate samples. These procedures include a newly proposed nonparametric rank-sum test and a generalized least squares test. Also considered are the following tests: ordinary least squares, Hotelling's T2, and a Bonferroni per-experiment error-rate approach. Applications are envisaged in which each variable represents a qualitatively different measure of response to treatment. The null hypothesis of no treatment difference is tested with power directed towards alternatives in which at least one treatment is uniformly better than the others. In all simulations the nonparametric procedure provided relatively good power and accurate control over the size of the test, and is recommended for general use. Alternatively, the generalized least squares procedure may also be useful with normally distributed data in moderate or large samples. A convenient expression for this procedure is obtained and its asymptotic relative efficiency with respect to the ordinary least squares test is evaluated.

0 comments Cited 144 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cognitive outcome following traumatic brain injury.

Sureyya S Dikmen, John Corrigan, Harvey Levin … (2015)

To determine whether an association exists between traumatic brain injury (TBI) sustained in adulthood and cognitive impairment 6 months or longer after injury. Systematic review of the published, peer-reviewed literature. From 430 articles, we identified 11 primary and 22 secondary studies that examined cognitive impairment by using performance measures for adults who were at least 6 months post-TBI. There was clear evidence of an association between penetrating brain injury and impaired cognitive function. Factors that modified this association included preinjury intelligence, volume of brain tissue lost, and brain region injured. There was also suggestive evidence that penetrating brain injury may exacerbate the cognitive effects of normal aging. We found clear evidence for long-term cognitive deficits associated with severe TBI. There was suggestive evidence that moderately severe brain injuries are associated with cognitive impairments. There was inadequate/insufficient evidence to determine whether an association exists between a single, mild TBI and cognitive deficits 6 months or longer postinjury. In adults, penetrating, moderate, and severe TBIs are associated with cognitive deficits 6 months or longer postinjury. There is insufficient evidence to determine whether mild TBI is associated with cognitive deficits 6 months or longer postinjury.

0 comments Cited 87 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Neurotrauma

Journal ID (iso-abbrev): J. Neurotrauma

Journal ID (publisher-id): neu

Title: Journal of Neurotrauma

Publisher: Mary Ann Liebert, Inc., publishers (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )

ISSN (Print): 0897-7151

ISSN (Electronic): 1557-9042

Publication date (Print): 01 October 2018

Publication date (Electronic): 24 September 2018

Publication date PMC-release: 24 September 2018

Volume: 35

Issue: 19

Pages: 2298-2305

Affiliations

[ ¹ ]Department of Physical Medicine and Rehabilitation, Indiana University School of Medicine , Indianapolis, Indiana.

[ ² ]Rehabilitation Hospital of Indiana , Indianapolis, Indiana.

[ ³ ]Department of Physical Medicine and Rehabilitation, Carolinas Rehabilitation , Carolinas HealthCare System, Charlotte, North Carolina.

[ ⁴ ]TIRR Memorial Hermann , Houston, Texas.

[ ⁵ ]Spaulding Rehabilitation Hospital , Boston, Massachusetts.

[ ⁶ ]Department of Rehabilitation Medicine, University of Washington , Seattle, Washington.

[ ⁷ ]Department of Physical Medicine and Rehabilitation, The Ohio State University , Columbus, Ohio.

[ ⁸ ]Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center , Dallas, Texas.

[ ⁹ ]Department of Neurological Surgery, University of Washington , Seattle, Washington.

[ ¹⁰ ]Department of Biostatistics, University of Washington , Seattle, Washington.

Author notes

[*]Address correspondence to: Flora M. Hammond, MD, Rehabilitation Hospital of Indiana 4141 Shore Drive, Indianapolis, IN 46254, flora.Hammond@ 123456rhin.com

Article

Publisher ID: 10.1089/neu.2018.5767

DOI: 10.1089/neu.2018.5767

PMC ID: 6157374

PubMed ID: 29742960

SO-VID: 3fd37a09-17ea-4f0c-ad01-e89dd605ce9c

License:

This Open Access article is distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

Amantadine Did Not Positively Impact Cognition in Chronic Traumatic Brain Injury: A Multi-Site, Randomized, Controlled Trial

Read this article at

Abstract

Related collections

Embodied Memory

Most cited references 18

Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury

Procedures for comparing samples with multiple endpoints.

Cognitive outcome following traumatic brain injury.

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 322

Cited by 16

Most referenced authors 230