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Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. Modafinil (100–200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4–16) days and initiated 14 (7–17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. −0.2 [6.32], P = 0.003). A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting. [ABSTRACT FROM AUTHOR]

For a subset of patients with severe acute brain injury (SABI) undergoing invasive mechanical ventilation, the primary barrier to successful extubation is depressed mental status. Amantadine is a neurostimulant that has been demonstrated to increase arousal and improve functional outcomes in patients with SABI. In this case series, we describe 5 patients with SABI and invasive mechanical ventilation who received amantadine as an agent to improve mental status to allow extubation. The primary barrier to extubation for all patients was depressed mental status. Median age was 77 (range 32 to 82). Primary diagnoses were ischemic stroke (n = 1), subdural hemorrhage (n = 2), intracerebral hemorrhage (n = 1), and traumatic brain injury (n = 1). Median Glasgow Coma Score was 7T prior to administration of amantadine and 10T on the day after amantadine was initiated, with improvements in eye-opening and motor response. Four patients displayed improvement in arousal and attention and were successfully extubated 1 to 4 days after initiation of amantadine (median 2 days). The fifth patient only displayed marginal improvement in mental status after starting amantadine, but was ultimately able to be extubated 7 days later. Amantadine may improve the likelihood of or reduce the time to successful extubation in patients with SABI., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

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 post-stroke (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 acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). Conclusions: Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings. [ABSTRACT FROM AUTHOR]

Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive review has been published. This systematic review describes amantadine and modafinil administration practices post-stroke, evaluates timing and impact on clinical effectiveness measures, and identifies the incidence of potential adverse drug effects. A librarian-assisted search of the MEDLINE (PubMed) and EMBASE databases identified all English-language publications with "amantadine" or "modafinil" in the title or abstract from inception through February 1, 2020. Publications meeting predefined Patient, Intervention, Comparator, Outcome (PICO) criteria were included: Patients (≥ 18 years of age post-stroke); Intervention (amantadine or modafinil administration); Comparison (pretreatment baseline or control group); Outcomes (cognitive or functional outcome). Amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of potential adverse drug effects were collected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance. Quantitative analyses were not performed due to heterogeneity in the clinical effectiveness measures; descriptive data are presented as number (percent) or median (interquartile range). Of 12,620 publications initially identified, 10 amantadine publications (n = 121 patients) and 12 modafinil publications (n = 120 patients) were included. Amantadine was initiated 39 (16, 385) days post-stroke, with most common initial doses of 100 mg once or twice daily (range 100–200 mg/day), and final daily dose of 200 (188, 200) mg/day. Modafinil was initiated 170 (17, 496) days post-stroke, with initial and final daily doses of 100 (100, 350) mg/day and 200 (100, 350) mg/day, respectively. The most common indication was consciousness disorders for amantadine (n = 3/10 publications; 30%) and fatigue for modafinil (n = 5/12; 42%). Forty unique clinical effectiveness measures (1.8 per study) with 141 domains (6.4 per study) were described across all studies. A positive response in at least one clinical effectiveness measure was reported in 70% of amantadine publications and 83% of modafinil publications. Only one publication each for amantadine (10%; n = 5 patients) and modafinil (8%; n = 21 patients) studied acutely hospitalized or ICU patients; both were randomized studies showing improvements in neurocognitive function for amantadine and fatigue for modafinil. Potential adverse drug effects were reported in approximately 50% of publications, most commonly visual hallucinations with amantadine (2% of patients) and dizziness (5% of patients) and dry eyes or mouth (5% of patients). Amantadine and modafinil may improve cognitive and functional recovery post-stroke, but higher-quality data are needed to confirm this conclusion, especially in the acute care setting. [ABSTRACT FROM AUTHOR]

We aimed to determine the potentially modifiable risk factors that are predictive of post-traumatic brain injury seizures in relation to the severity of initial injury, neurosurgical interventions, neurostimulant use, and comorbidities. This retrospective study was conducted on traumatic brain injury (TBI) patients admitted to a single center from March 2008 to October 2017. We recruited 151 patients from a multiracial background with TBI, of which the data from 141 patients were analyzed, as 10 were excluded due to incomplete follow-up records or a past history of seizures. Of the remaining 141 patients, 33 (24.4%) patients developed seizures during long-term follow up post-TBI. Young age, presence of cerebral contusion, Indian race, low Glasgow Coma Scale (GCS) scores on admission, and use of neurostimulant medications were associated with increased risk of seizures. In conclusion, due to increased risk of seizures, younger TBI patients, as well as patients with low GCS on admission, cerebral contusions on brain imaging, and those who received neurostimulants or neurosurgical interventions should be monitored for post-TBI seizures. While it is possible that these findings may be explained by the differing mechanisms of injury in younger vs. older patients, the finding that patients on neurostimulants had an increased risk of seizures will need to be investigated in future studies.