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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 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]