The Effect of Oral Administration of Amantadine on Neurological Outcome of Patients With Diffuse Axonal Injury in ICU

Abstract

Traumatic brain injury is a major cause of death and disability in adults. This study investigated the effect of oral administration of amantadine on the neurological outcomes of patients with diffuse axonal injury (DAI) in the intensive care unit (ICU). This double-blind clinical trial was conducted in the ICU of Imam Hospital in Urmia. Patients with DAI were intubated and received mechanical ventilation in the ICU. They were divided into 2 groups: patients receiving amantadine (A) and placebo (P). The acquired data were analyzed using SPSS, P < .05 significant level. Findings showed no significant difference between the 2 groups in age and sex. There was no significant difference between the mean Glasgow Coma Scale (GCS) at the time of admission and discharge, and the mean Glasgow Outcome Scale (GOS) of the patients in 2 groups. No significant difference was observed in the duration of mechanical ventilation, hospitalization, and mortality in both groups (P > .05) in ICU. However, there was a significant difference between the mean GCS at the time of admission and discharge and death. Also, significant differences existed between the mean GOS in discharged and deceased patients (P = .001). This study showed no significant difference between the mean GCS at the time of admission and discharge and the mean GOS of the discharged patients and the mortality rate in the 2 groups. However, there were clear statistical differences between these variables in discharged and deceased patients. It is recommended that further studies are conducted with a larger sample size.

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury

“…AMA continues to be investigated as a therapeutic agent for improving level of consciousness and functional recovery for persons remaining in states of DoC. 3 – 6 The seizure risk for rTMS paired with AMA is unknown; theoretically, AMA by itself may lower seizure threshold. A recent systematic review reports a 0.7% prevalence of seizure (2/259 patients) with 100 to 200 mg twice a day of AMA.…”

Pharmacologic Therapies to Promote Recovery of Consciousness

“…10 Two additional smaller randomized controlled trials have investigated the efficacy of amantadine during the acute hospitalization. 19,26 Similar to the landmark clinical trial discussed earlier, Ghalaenovi et al found a higher Glasgow Coma Scale (GCS) score change in patients receiving amantadine (n ¼ 19) versus placebo (n ¼ 21) between day 1 and day 7, suggesting a faster time to recovery. 19 In addition, the authors affirmed previous findings that no difference was observed in long-term functional outcome measures reported at 6 months after a 6-week treatment period, suggesting that while amantadine may accelerate the recovery of arousal, this does not change long-term outcomes.…”

“…While Ghalaenovi and colleagues evaluated a lower dose of amantadine (100 mg twice daily), Abbasivash et al evaluated a higher amantadine dose (200 mg twice daily) in patients with severe TBI ( n = 33) compared with placebo ( n = 33) that was continued until extubation or recovery to GCS > 8. 26 Patients in this study were followed up only to hospital discharge and improvements in arousal beyond that time were not reported, but no difference was observed in the duration of mechanical ventilation, GCS, or Glasgow Outcome Scale (GOS) scores at hospital discharge (mean hospital length of stay: 29 and 32 days, respectively).…”

“…21 While initial case reports showed remarkable improvement in behaviors such as eye opening, command following, and object manipulation after amantadine initiation in patients with DoC, larger trials demonstrated mixed results. 11,[17][18][19][22][23][24][25][26] Overall, studies of amantadine in patients with DoC are heterogenous in study design, populations studied, outcomes measured, and follow-up duration. Despite this, amantadine is the only pharmacologic stimulant therapy that has been shown in randomized controlled trials to promote functional recovery from DoC.…”

Improved survival in intensive care unit in severe COVID-19 associated with amantadine use - retrospective study

“…Furthermore, in the study by Rahman Abbasivash et al, the effect of oral administration of amantadine on the neurological outcomes of patients with diffuse axonal injury (DAI) in the intensive care unit was evaluated. ( Abbasivash et al, 2019 ) All patients in this study were intubated and received mechanical ventilation. They were divided into 2 groups: patients receiving amantadine and placebo.…”