Amantadine

Gualtieri, Thomas; Chandler, Mark; Coons, Tena B.; Brown, Lloyd T.

doi:10.1097/00002826-198908000-00003

Cited by 90 publications

(7 citation statements)

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“…A number of retrospective chart reviews, case-control studies, or case reports in patients with disorders of consciousness remain in concordance with the results of the aforementioned RCTs [124,[146][147][148][149][150][151][152][153][154][155][156][157]. Furthermore, amantadine-induced specific metabolic changes in affected brain areas of TBI patients, which were correlated with some clinical improvements [142,149].…”

Section: Clinical Studiessupporting

confidence: 58%

“…Later, efficacy in TBI has been suggested initially by Gualtieri and colleagues based on clinical observations [123,124]. It is probably not surprising given the fact that neuroprotection by amantadine has been suggested in various conditions such as Parkinson's disease, stroke, or infectious disease [125][126][127][128][129][130].…”

Section: Preclinical and Clinical Evidence Of Amantadine Efficacy In Tbimentioning

confidence: 99%

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Amantadine for Traumatic Brain Injury – Supporting Evidence and Mode of Action

Dekundy,

Pichler,

El Badry

et al. 2024

Preprint

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Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have severe impact on the patient’s quality of life. The current review summarizes evidence for utility of amantadine in TBI in connection to its mechanism of action. Amantadine combining multiple mechanisms of action may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as infusion which may be of particular benefit in unconscious patients with TBI, due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: Can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers these questions.

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Section: Clinical Studiessupporting

confidence: 58%

Section: Preclinical and Clinical Evidence Of Amantadine Efficacy In Tbimentioning

confidence: 99%

Amantadine for Traumatic Brain Injury – Supporting Evidence and Mode of Action

Dekundy,

Pichler,

El Badry

et al. 2024

Preprint

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“…A year later, the same team published positive results showing reduced experienced tiredness as well as lower distraction and aggressiveness in a cohort of 30 subacute and chronic TBI patients. From the cohort, 14 patients were referred to as being "unequivocal responders", and five responded favorably but presented with important side effects such as irritability, rigidity and seizures [50]. Subsequently, a third clinical trial with amantadine published in 1994 recruited 12 TBI patients with "high agitation" (n=3) or "low arousal" (n=9).…”

Section: First Clinical Trials In Patients With Acquired Brain Injuriesmentioning

confidence: 99%

Amantadine, Apomorphine and Zolpidem in the Treatment of Disorders of Consciousness

Gosseries

Charland‐Verville

Thonnard

et al. 2013

CPD

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Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to enhance our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition.

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“…Amantadine has demonstrated reasonable safety, low cost, lack of sedating effects, rapid therapeutic dosing and effect, and ability to determine nonresponse quickly. 16 A single-site, randomized-controlled trial by Hammond et al 17 studied 76 individuals at least 6 months post-TBI who received amantadine (n = 38) 100 mg twice daily versus placebo (n = 38) for 28 days. Significant differences favoring amantadine were found for the observer-rated Neuropsychiatric Inventory Irritability (NPI-I) Most Problematic.…”

Section: Introductionmentioning

confidence: 99%

Assessing the benefits and risks of amantadine for irritability and aggression after traumatic brain injury

Hammond,

Zafonte,

Sherer

et al. 2024

PM&R

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ObjectiveTo quantify the benefits versus harms of amantadine in the treatment of irritability and aggression following traumatic brain injury.MethodsSecondary 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. Specifically, NNTB values were calculated using number of individuals with improvement on the Clinician Global Impressions‐Global Improvement scale (GI). NNTB values were computed using number of individuals with worsening on the GI and experiencing serious and any adverse events.ResultsBased on clinician ratings, on average for every 6 patients treated with amantadine rather than placebo, 1 extra patient would be expected to improve (NNTB=6.4; 95% CI: [3.3, 76.8]). More participants in the placebo group worsened than in the amantadine group, but the result was not statistically significant (NNTH=‐92.4; 95% CI: [NNTB ‐32.9 to ‐infinity to NNTH ‐19.2]). The amantadine and placebo groups did not differ on the numbers of adverse events experienced during the trial.ConclusionClinician ratings suggest modest benefit of amantadine 100mg twice daily with low risk to appropriately selected patients with adequate renal clearance. Thus, amantadine should be considered a treatment option for the experienced brain injury clinician. These data may support treatment decisions when a pharmaceutical agent is being considered to control irritability/aggression.This article is protected by copyright. All rights reserved.

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Amantadine

Cited by 90 publications

References 0 publications

Amantadine for Traumatic Brain Injury – Supporting Evidence and Mode of Action

Amantadine for Traumatic Brain Injury – Supporting Evidence and Mode of Action

Amantadine, Apomorphine and Zolpidem in the Treatment of Disorders of Consciousness

Assessing the benefits and risks of amantadine for irritability and aggression after traumatic brain injury

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