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Amantadine and TBI

Flora M Hammond, James F Malec, Ross D Zafonte, Mark Sherer, Jennifer Bogner, Sureyya Dikmen, Marybeth P Whitney, Kathleen R Bell, Susan M Perkins, Elizabeth A Moser
OBJECTIVE: To assess the effects of amantadine on anger and aggression among individuals with a chronic traumatic brain injury (TBI). METHODS: A cohort of 118 persons with chronic TBI (>6 months postinjury) and moderate-severe aggression selected from a larger cohort of 168 participants enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine 100 mg twice daily (n = 82) versus placebo (n = 86) for treatment of irritability were studied...
September 2017: Journal of Head Trauma Rehabilitation
Cole Vonder Haar, Frederick C W Lam, Wendy K Adams, Lara-Kirstie Riparip, Sukhbir Kaur, Michael Muthukrishna, Susanna Rosi, Catharine A Winstanley
Traumatic brain injury (TBI) affects millions yearly, and is increasingly associated with chronic neuropsychiatric symptoms. We assessed the long-term effects of different bilateral frontal controlled cortical impact injury severities (mild, moderate, and severe) on the five-choice serial reaction time task, a paradigm with relatively independent measurements of attention, motor impulsivity, and motivation. Moderately- and severely injured animals exhibited impairments across all cognitive domains that were still evident 14 weeks postinjury, while mild-injured animals only demonstrated persistent deficits in impulse control...
November 16, 2016: ACS Chemical Neuroscience
Stephanie Stelmaschuk, Mary Colleen Will, Tamara Meyers
Traumatic brain injury (TBI) is a leading cause of injury, disability, and death in the United States. Amantadine is an established dopamine agonist that supports neurological function. The purpose of this literature review was to determine whether amantadine improves cognitive function post-TBI. PubMed and CINAHL were used to search the literature for articles using amantadine to treat TBI from 1994 to 2004. Outcomes were summarized and the evidence was appraised. Although earlier studies from 1994 to 2003 were lower-level studies and recommended further research on treatment of cognitive dysfunction in TBI, the literature from 2004 to present generally concluded that amantadine improved cognitive function related to arousal, memory, and aggression...
July 2015: Journal of Trauma Nursing: the Official Journal of the Society of Trauma Nurses
Musa Basseer Sami, Rafey Faruqui
OBJECTIVE: Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials. METHODS: We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function...
December 2015: Acta Neuropsychiatrica
Flora M Hammond, Mark Sherer, James F Malec, Ross D Zafonte, Marybeth Whitney, Kathleen Bell, Sureyya Dikmen, Jennifer Bogner, Jerry Mysiw, Rashmi Pershad
This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons ≥6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale...
August 15, 2015: Journal of Neurotrauma
Scott D Spritzer, Carolyn L Kinney, John Condie, Kay E Wellik, Charlene R Hoffman-Snyder, Dean M Wingerchuk, Bart M Demaerschalk
BACKGROUND: Research into traumatic brain injury (TBI) has increased significantly. Diagnostic testing and therapeutics for patients with severe TBI are 2 areas on which there is increasing focus. Amantadine hydrochloride is one treatment considered to have potential therapeutic value in this patient population. OBJECTIVE: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions...
January 2015: Neurologist
Liang Tan, Hongfei Ge, Jun Tang, Chuhua Fu, Wangsheng Duanmu, Yujie Chen, Rong Hu, Jianfeng Sui, Xin Liu, Hua Feng
Traumatic brain injury (TBI) often results in multiple neuropsychiatric sequelae, including cognitive, emotional, and behavioral problems. Among them, depression is a common psychiatric symptom, and links to poorer recovery. Amantadine, as an antiparkinsonian, increases dopamine release, and blocks dopamine reuptake, but has recently received attention for its effectiveness as an antidepressant. In the present study, we first induced a post-TBI depression rat model to probe the efficacy of amantadine therapy in reducing post-TBI depression...
February 15, 2015: Behavioural Brain Research
Rita Formisano, Nathan D Zasler
Amantadine hydrochloride is one of the most commonly used drugs in the pharmacotherapeutic treatment of disorders of consciousness (DOCs) following traumatic brain injury (TBI). Indeed, its actions as a pro-dopaminergic drug and as an N-methyl-D-aspartate antagonist makes amantadine an interesting candidate to improve consciousness and responsiveness in individuals with DOC, including vegetative state and minimally conscious state. Giacino et al (N Engl J Med. 2012;366(9):819-826) recently reported that amantadine was able to accelerate the functional recovery course of subjects after TBI with DOC, during a 4-week treatment period...
July 2014: Journal of Head Trauma Rehabilitation
Eagle Yi-Kung Huang, Pi-Fen Tsui, Tung-Tai Kuo, Jing-Jr Tsai, Yu-Ching Chou, Hsin-I Ma, Yung-Hsiao Chiang, Yuan-Hao Chen
AIMS: To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. MATERIALS AND METHODS: In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury...
2014: PloS One
P Gunnar Brolinson
OBJECTIVE: To systematically review the evidence for rest, treatment, and rehabilitation after sport-related concussion. DATA SOURCES: Nine databases including PubMed, Cochrane Central Register of Controlled Trials, Sport Discus, and Web of Science were searched for studies that evaluated the effect of rest separately from the effects of treatment and/or rehabilitation, using words related to concussion, mild traumatic brain injury, rest, treatment outcome, and therapy...
January 2014: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
Flora M Hammond, Allison K Bickett, James H Norton, Rashmi Pershad
BACKGROUND: Following traumatic brain injury (TBI), individuals may experience chronic problems with irritability or aggression, which may need treatment to minimize the negative impact on their relationships, home life, social interactions, community participation, and employment OBJECTIVE: : To test the a priori hypothesis that amantadine reduces irritability (primary hypothesis) and aggression (secondary hypothesis) among individuals greater than 6 months post-TBI METHODS:: A total of 76 individuals greater than 6 months post-TBI referred for irritability management were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine (n = 38) versus placebo (n = 38)...
September 2014: Journal of Head Trauma Rehabilitation
Erika Y Breceda, Alexander W Dromerick
PURPOSE OF REVIEW: The purpose of this review is to provide an update on the latest neurorehabilitation literature for motor recovery in stroke and traumatic brain injury to assist clinical decision making and assessing future research directions. RECENT FINDINGS: The emerging approach to motor restoration is now multimodal. It engages the traditional multidisciplinary rehabilitation team, but incorporates highly structured activity-based therapies, pharmacology, brain stimulation and robotics...
December 2013: Current Opinion in Neurology
Giulia Cossu
Traumatic brain injury is a leading cause of death and disability. Optimizing the recovery from coma is a priority in seeking to improve patients' functional outcomes. Standards of care have not been established: pharmacological interventions, right median nerve and sensory stimulation, dorsal column stimulation (DCS), deep brain stimulation, transcranial magnetic stimulation, hyperbaric oxygen therapy and cell transplantation have all been utilized with contrasting results. The aim of this review is to clarify the indications for the various techniques and to guide the clinical practice towards an earlier coma arousal...
April 2014: British Journal of Neurosurgery
John Whyte, Annette M Nordenbo, Kathleen Kalmar, Barbara Merges, Emilia Bagiella, Helena Chang, Stuart Yablon, Sooja Cho, Flora Hammond, Allen Khademi, Joseph Giacino
OBJECTIVE: To assess the incidence of medical complications in patients with recent traumatic disorders of consciousness (DOCs). DESIGN: Data on adverse events in a placebo controlled trial of amantadine hydrochloride revealed no group difference, which allowed these events to be reanalyzed descriptively as medical complications experienced by the 2 groups collectively. SETTING: Eleven clinical facilities in the United States, Denmark, and Germany with specialty rehabilitation programs for patients with DOCs...
October 2013: Archives of Physical Medicine and Rehabilitation
Tao Wang, Xian-Jian Huang, Ken C Van, Gregory T Went, Jack T Nguyen, Bruce G Lyeth
This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day...
February 15, 2014: Journal of Neurotrauma
Sheik Hosenbocus, Raj Chahal
OBJECTIVE: To review published literature regarding the pharmacology and use of amantadine in child and adolescent psychiatry. METHOD: A LITERATURE SEARCH OF SEVERAL DATABASES (PUBMED, PSYCHINFO, CINAHL, MEDLINE, PSYCARTICLES, BIOMEDICAL REFERENCE COLLECTION AND ACADEMIS SEARCH COMPLETE) WAS CONDUCTED WITH THE SEARCH TERMS: 'amantadine' with limits: English language, Human trials, all child (aged 0-18 years). The search was later expanded to include 'Adults' and additional relevant articles were selected from reference lists...
February 2013: Journal of the Canadian Academy of Child and Adolescent Psychiatry
Joseph T Giacino, John Whyte, Emilia Bagiella, Kathleen Kalmar, Nancy Childs, Allen Khademi, Bernd Eifert, David Long, Douglas I Katz, Sooja Cho, Stuart A Yablon, Marianne Luther, Flora M Hammond, Annette Nordenbo, Paul Novak, Walt Mercer, Petra Maurer-Karattup, Mark Sherer
BACKGROUND: 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. METHODS: 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...
March 1, 2012: New England Journal of Medicine
Patricia Wheaton, Jane L Mathias, Robert Vink
Pharmacological treatments that are administered to adults in the postacute stage after a traumatic brain injury (TBI) (≥4 weeks after injury) have the potential to reduce persistent cognitive and behavioral problems. While a variety of treatments have been examined, the findings have yet to be consolidated, hampering advances in the treatment of TBI. A meta-analysis of research that has investigated the cognitive and behavioral effects of pharmacological treatments administered in the later stage after TBI was therefore conducted...
December 2011: Journal of Clinical Psychopharmacology
Anne Julie Frenette, Salmaan Kanji, Laura Rees, David R Williamson, Marc M Perreault, Alexis F Turgeon, Francis Bernard, Dean A Fergusson
In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, comparing DA to either placebo, standard treatment, or another active comparator...
January 1, 2012: Journal of Neurotrauma
Ashok Krishnamoorthy, David Craufurd
Apathy is one of the most prevalent neurobehavioral symptoms in Huntington's disease (HD), occurring in approximately 70% of the symptomatic HD population. Apathy scores in patients with HD are highly correlated with duration of illness, suggesting that apathy is an inevitable consequence of advanced disease. Although less distressing than symptoms like depression and less disruptive than irritability or aggression, apathy has a considerable adverse impact on those affected with HD because it leads to a decrease of the goal-directed behaviors that contribute much to the day-to-day quality of life...
October 2011: Current Treatment Options in Neurology
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