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In a randomized controlled trial, the effects of amantadine and citicoline and their combinations were compared on arousal and behavioral consequences in the early phase of moderate TBI. Patients were divided into three groups (15 patients each) with moderate TBI; group C (citicoline) received 1 g citicoline every 12 h for 7 days. Participants received 500 mg oral drops syrup twice a day or the same dose as oral drops syrup of citicoline through a nasogastric tube (NG) or percutaneous endoscopic gastrostomy (PEG) tube in a total dose of 1000\u2009mg\/day for a 30-day study period. Group A (amantadine) received 200 mg of amantadine sulfate in a 500 mL solution every 12 h for 7 days. Participants received two 100-mg tablets twice a day or through an NG or PEG tube as 400\u2009mg for a 30-day study period. Group CA (Citicoline + Amantadine) received 1 g citicoline every 12 h and 200 mg of amantadine sulfate in a 500 mL solution every 12 h for 7 days, then 500 mg of citicoline syrup twice daily plus 200 tablets twice daily amantadine for a 30-day study period. Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), and mini-mental state (MMS) were used to assess the patient\u2019s conditions on the 1st, 4th, and 7th days (acute phase) in the intensive care unit (ICU), then 30 days after injury. The endpoints of the study were either the death of the patient or the completion of the study period of 30 days. The number of mechanically ventilated patients, the number of ventilated days, mortality, total ICU, and hospital length of stay were measured. GCS on days 4, 7, and 30 were significantly higher in group A and group CA compared with group C, with no significant differences between groups A and CA. DRS in days 4 and 7 became significantly lower in groups A and CA compared with group C, with no significant differences between groups A and CA. MMS in days 4, 7, and 30 became significantly lower in group C, with no significant differences between groups A and CA. The duration of mechanical ventilation, ICU, and hospital stay was significantly longer in group C, with no significant differences between groups A and CA. This study showed that amantadine alone or in combination with citicoline has a favorable effect on the recovery of consciousness and cognitive behavior in patients with moderate TBI and reduces the mechanical ventilation days, hospital, and ICU length of stay.<\/jats:p>","DOI":"10.1177\/08977151251375914","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T22:30:21Z","timestamp":1759271421000},"page":"68-77","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Citicoline\u2013Amantadine Trial in Traumatic Brain Injury: A Prospective Randomized Study"],"prefix":"10.1177","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-875X","authenticated-orcid":false,"given":"Dina Salah Eldin Mahmoud","family":"Badre","sequence":"first","affiliation":[{"name":"Department of Anesthesia, ICU and Pain, Ain Shams University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa Ahmed Khairy","family":"Elbeialy","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, ICU and Pain, Ain Shams University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Fathy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ain Shams University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02689-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.06.030973"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.3019"},{"key":"e_1_3_3_5_2","first-page":"599","article-title":"Antiviral agents for influenza A","volume":"258","author":"Morbidity and Mortality Weekly Report (MMWR)","year":"1987","unstructured":"Morbidity and Mortality Weekly Report (MMWR). 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