Effect of Amantadine on Agitation in Critically Ill Patients With Traumatic Brain Injury

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This study aimed to compare the presence of agitation in traumatic brain injury patients treated with amantadine with those not treated with amantadine in the intensive care unit (ICU).


This was a retrospective cohort study conduced in a trauma ICU of a tertiary care institution in the United States. Patients who received amantadine were compared with patients who did not receive amantadine. The primary outcome measure was the presence of agitation, defined as the Richmond Agitation Sedation Scale score of +2 or higher. Secondary comparisons included haloperidol use, benzodiazepine use, opioid use, and ICU length of stay.


A total of 139 patients were included in the study cohort (70 patients in the amantadine group, 69 patients in the no-amantadine group). There were more patients who had agitation in the amantadine group (38% vs 14%, P = 0.018). Patients who received amantadine received more opioids in fentanyl equivalents (10.3 [interquartile range {IQR}, 6.3–20.4] μg/kg vs 7.4 [IQR, 2.1–12.6] μg/kg, P = 0.009) and had a longer ICU length of stay (4.5 [IQR, 3–10] days vs 3 [IQR, 2–5] days, P = 0.010). Haloperidol use and benzodiazepine use were similar between groups.


The early use of amantadine after traumatic brain injury may increase the risk of agitation. This could increase opioid consumption and ICU length of stay.

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