Prescribing Multiple Neurostimulants during Rehabilitation for Severe Brain Injury

Herrold, Amy A.; Pape, Theresa; Guernon, Ann; Mallinson, Trudy; Collins, Eileen G.; Jordan, Neil

doi:10.1155/2014/964578

Cited by 13 publications

(13 citation statements)

References 31 publications

(38 reference statements)

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“…Beside amantadine, the administration of one or more neurostimulants (i.e., amantadine, bromocriptine, levodopa, methylphenidate, and modafinil) has also been explored in a retrospective study in a cohort of 115 patients with DOC (< 180 days post-onset). 13 The number of neurostimulants did not induced meaningful behavioral improvement in this observational study.…”

Section: Amantadine and Other Neurostimulantsmentioning

confidence: 52%

“…Amantadine (dopamine agonist and NMDA antagonist [11][12][13][14], intrathecal baclofen (GABA agonist 15 ), zolpidem (nonbenzodiazepine GABA agonist 16,17 ), midazolam (benzodiazepine GABA agonist 18 ) and ziconotine (calcium channel blocker 19 ) have been employed to improve the level of consciousness and functional recovery in patients with DOC.…”

Section: Pharmacological Treatmentsmentioning

confidence: 99%

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Therapeutic interventions in patients with prolonged disorders of consciousness

Thibaut

Schiff

Giacino

et al. 2019

The Lancet Neurology

269

229

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The management of patients with severe brain injuries and prolonged disorders of consciousness (DOC) raises important issues particularly with respect to their therapeutic options. The lack of treatment is challenged by new clinical and neuroimaging data indicating that some patients with prolonged DOC may benefit from therapeutic interventions, even years after the injury. The majority of the studies aiming at improving patients' level of consciousness and functional recovery includes behavioural and brain imaging open-label trials and case-reports, but several randomized clinical trials (RCT) have been conducted, especially using non-invasive brain stimulation. Only a couple of RCTs focused on the effects of drugs or sensory stimulation approaches, and only two Class II studies, on amantadine and transcranial direct current stimulation, have been published. While new therapeutic approaches seem to be valuable for patients with prolonged DOC, optimized stimulation parameters, alternative drugs or rehabilitation strategies still need to be tested and validated.

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Section: Amantadine and Other Neurostimulantsmentioning

confidence: 52%

Section: Pharmacological Treatmentsmentioning

confidence: 99%

Therapeutic interventions in patients with prolonged disorders of consciousness

Thibaut

Schiff

Giacino

et al. 2019

The Lancet Neurology

269

229

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“…Whether adding a second neurostimulant (if no improvement is observed from the initial neurostimulant) adds benefit, risk, neither, or both is unclear. Herrold and colleagues retrospectively evaluated 115 TBI patients treated with neurostimulants in a rehabilitation center, finding that those treated with multiple agents had no better outcome than those treated with a single medication [34]. Given the lack of an untreated control group in this retrospective study, we cannot be certain that any improvements resulted from the medications and it is possible they reflect the natural phase of recovery over time after stroke.…”

Section: Discussionmentioning

confidence: 93%

Amantadine and Modafinil as Neurostimulants Following Acute Stroke: A Retrospective Study of Intensive Care Unit Patients

et al. 2020

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Background/Objective: Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. Methods: Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. Results: A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days poststroke (range 1-27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to

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“…Other types of pharmacologic drugs, such as baclofen (GABA B ) [76][77][78], midazolam (GABA A ) [79], amitriptyline [80], desipramine, protriptyline [81] (norepinephrine and serotonin), and modafinil [82] (norepinephrine, dopamine, and orexin), have also shown variable benefit in small-sample studies. It is unknown whether the use of multiple stimulants in combination provides therapeutic benefit over use of a single stimulant [83]. Additionally, new types of drugs are emerging as potential candidates to promote recovery of consciousness.…”

Section: Pharmacologic Agents: State Of the Sciencementioning

confidence: 99%

Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions

et al. 2021

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Background/Objective For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis. Methods We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development. Results Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints. Conclusions This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.

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Prescribing Multiple Neurostimulants during Rehabilitation for Severe Brain Injury

Cited by 13 publications

References 31 publications

Therapeutic interventions in patients with prolonged disorders of consciousness

Therapeutic interventions in patients with prolonged disorders of consciousness

Amantadine and Modafinil as Neurostimulants Following Acute Stroke: A Retrospective Study of Intensive Care Unit Patients

Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions

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