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

Gramish, Jawaher A. PharmD*; Kopp, Brian J. PharmD; Patanwala, Asad E. PharmD

doi: 10.1097/WNF.0000000000000242
Original Articles

Objective 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).

Methods 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.

Results 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.

Conclusions 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.

*Pharmaceutical Care Services, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia; †Department of Pharmacy Services, Banner University Medical Center Tucson; and ‡Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ.

Address correspondence and reprint requests to Asad E. Patanwala, PharmD, MPH, 1295 N. Martin, PO Box 210202, Tucson, AZ 85721; E-mail:

Conflicts of Interest and Source of Funding: None.

Author Contribution: A.P. and B.K. conceived of the study. All authors contributed to the study design. J.G. collected the data. A.P. conducted the data analysis. J.G. wrote the first draft of the manuscript. A.P. and B.K. contributed to its revision. All authors approved the final version of the manuscript.

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