Amantadine and TBI

The purpose of this study was to differentiate clinically meaningful improvement or deterioration from normal fluctuations in patients with disorders of consciousness (DoC) following severe brain injury. We computed indices of responsiveness for the Coma Recovery Scale-Revised (CRS-R) using data from a clinical trial of 180 participants with DoC. We used CRS-R scores from baseline (enrollment in a clinical trial) and a four-week follow-up assessment period for these calculations. To improve precision, we transformed ordinal CRS-R total scores (0 to 23 points) to equal-interval measures on a 0-to-100-unit scale using Rasch Measurement theory...

INTRODUCTION: TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness.6 It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition...

BACKGROUND: Severe disorders of consciousness (sDoC) are a common sequela of aneurysmal subarachnoid hemorrhages (aSAH), and amantadine has been used to improve cognitive recovery after traumatic brain injury. OBJECTIVE: This study evaluated the effect of amantadine treatment on consciousness in patients with sDoC secondary to aSAH. METHODS: This double-center, randomized, prospective, cohort study included patients ≥ 18 years old with sDoC after aSAH from February 2020 to September 2023...

INTRODUCTION: Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of guidelines for types of monitoring or neuroprotective therapy. The aim of this pilot study was to assess its feasibility and, furthermore, to evaluate the impact of Cerebrolysin on the following clinical outcomes: length of stay, Glasgow Outcome Scale (GOS) and mortality. METHODS: A cohort of 56 patients was included in this non-randomised, real-time, pre-post-interventional study...

OBJECTIVE: To quantify the benefits versus harms of amantadine in the treatment of irritability and aggression following traumatic brain injury. METHODS: Secondary outcome data from a randomized controlled multi-site trial of amantadine 100 mg twice daily were used to calculate Number-Needed-To-Treat (NNT). Given prior findings of positive clinician-perceived effects and low incidence of adverse events, we hypothesized low Number-Needed-To-Treat for Benefit (NNTB; high benefit) and high Number-Needed-To-Treat for Harm (NNTH; low risk) based on the clinician ratings, supporting the use of amantadine in clinical practice...

Environmental enrichment (EE) facilitates motor and cognitive recovery after traumatic brain injury (TBI). Historically, EE has been provided immediately and continuously after TBI, but this paradigm does not model the clinic where rehabilitation is typically not initiated until after critical care. Yet, treating TBI early may facilitate recovery. Hence, we sought to provide amantadine (AMT) as a bridge therapy before commencing EE. It was hypothesized that bridging EE with AMT would augment motor and cognitive benefits...

Pharmacologic treatment of disorders of consciousness remains a critical but challenging task for clinicians. Amantadine has been shown to promote the rate of neurologic recovery for patients with traumatic disorders of consciousness when administered between 4 and 16 weeks, as demonstrated by a well-designed randomized control trial. While there are no large, randomized controlled trials to support the use of other dopaminergic medicines (bromocriptine, levodopa, apomorphine), there is a large body of literature implicating their role in improving alertness and responsiveness in disorders of consciousness...

BACKGROUND: Amantadine is used in the post-acute care setting to improve cognitive function after a traumatic brain injury. Its utility in the acute postinjury period is unknown. In this pilot study, we sought to examine the effect of amantadine on short-term cognitive disability among patients with a severe traumatic brain injury and hypothesized that patients receiving amantadine would have a greater improvement in disability throughout their acute hospitalization. METHODS: We performed a prospective, observational study of patients ≥18 years with severe traumatic brain injury (Glasgow Coma Scale ≤8) at a level I trauma center between 2020 and 2022...

OBJECTIVES: Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs. METHODS: This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases...

OBJECTIVES: Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs. METHODS: This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases...

Symptoms after mild traumatic brain injury (MTBI) can persist for greater than 1 month in up to 20% of individuals, yet there are no current medications approved by the Food and Drug Administration for treatment of specific concussion related sequelae. Amantadine, a dopamine agonist and N-Methyl-D-aspartate antagonist, is increasingly being used as a treatment option for individuals with traumatic brain injury across the spectrum of injury severity. This case report describes a 22-year-old individual who sustained an MTBI without loss of consciousness or post-traumatic amnesia after striking their head against a metal cabinet...

In this report, we present a case series involving four pediatric patients who sustained a traumatic brain injury (TBI) and required intensive care unit admission immediately after the injury. In each of the four cases, amantadine was started during the acute care hospital admission to address agitation. Cases were retrieved from the electronic medical record at the Children's Hospital of Philadelphia between July 1, 2020, and October 31, 2022. This case series describes clinical data on TBI presentation, amantadine administration, patient behavior, and hospital course relating to agitation...

BACKGROUND: Persisting coma is a common complication in (neuro)intensive care in neurological disease such as acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. Amantadine acts as a nicotinic receptor antagonist, dopamine receptor agonist and non-competitive N-Methyl-D-aspartate receptor antagonist. Amantadine is a long-known drug, originally approved for treatment of influenza A and Parkinson`s Disease. It has been proven effective in improving vigilance after traumatic brain injury...

BACKGROUND: Disruption of dopamine neurotransmission is associated with functional impairment after severe traumatic brain injury (sTBI). This has prompted the study of dopamine agonists, such as amantadine, to assist recovery of consciousness (RoC). Randomized trials have mostly addressed the post-hospital setting, with inconsistent findings. Therefore, we evaluated the efficacy of early amantadine administration on RoC after sTBI. METHODS: We searched the medical records of all sTBI patients admitted to our hospital between 2010-2021 who survived ten days post-injury...

Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions...

Neuroleptic malignant syndrome (NMS), a potentially life-threatening neurological emergency characterized by muscle rigidity, altered mental status (AMS), autonomic instability, and hyperthermia, is most commonly precipitated by high-potency first-generation antipsychotics due to central dopamine receptor blockade. There is a heightened risk of NMS in animals with ischemic brain injury (IBI) or traumatic brain injury (TBI) due to the resulting death of dopaminergic neurons from injury and the dopamine receptor blockade elicited upon recovery...

Advent of the acute respiratory coronavirus SARS-CoV-2 has resulted in the search for novel antiviral agents and in the repurposing of existing agents with demonstrated efficacy against other known coronaviruses in the search for an agent with antiviral activity for use during the COVID-19 pandemic. Adamantanes including amantadine, rimantadine, and memantine have well-established benefit in the treatment of neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD) and fatigue related to Multiple sclerosis (MS) all of which are known comorbidities related to COVID-19 Moreover, results of basic pharmacological studies both in vitro and in vivo reveal that amantadine has the potential to inhibit SARS-CoV-2 via down-regulation of host-cell proteases resulting in impaired viral genome release into the host cell and via amantadine's property as an NMDA receptor antagonist resulting in the prevention of the acute lung injury and respiratory distress that is characteristic of COVID-19...

BACKGROUND: While systematic reviews have examined medication effectiveness for post-traumatic headache (PTH), they have not assessed tolerability. OBJECTIVE: To conduct a scoping review to characterize the adverse effects of pharmacotherapy for PTH. METHODS: CINAHL, CMA Infobase, Cochrane Library, Embase, Epistemonikos, MEDLINE, PEDro, PsycInfo, Scopus, SportDiscus, TRIP and the University of York Center for Reviews and Dissemination were searched...

INTRODUCTION: Moderate to severe traumatic brain injury (MS-TBI) commonly causes disruption in aspects of attention due to its diffuse nature and injury to frontotemporal and midbrain reticular activating systems. Attentional impairments are a common focus of cognitive rehabilitation, and increased awareness of evidence is needed to facilitate informed clinical practice. METHODS: An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated guidelines for the management of attention in adults, as well as a decision-making algorithm, and an audit tool for review of clinical practice...

WHAT IS KNOWN AND OBJECTIVE: Traumatic brain injury (TBI) is a major cause of disability, and it has been associated with agitation and aggression. In a previous study, we reviewed the literature to identify evidence-based pharmacological agents for treatment of agitation in TBI. Based on the results of our previous study that summarizes the findings of several systematic reviews, the use of haloperidol and benzodiazepines is not supported by the available evidence while the use of amantadine, beta blockers, antiepileptics and methylphenidate is supported by the limited available evidence...