LAUSR

Research Objectives To explore the benefits versus harms of amantadine in the treatment of irritability and aggression. Design Parallel-group, randomized, double-blind, placebo-controlled trial of amantadine versus placebo. Setting Outpatient. Participants 168 individuals with chronic TBI and irritability (amantadine n=82 versus placebo n=86). Interventions Amantadine 100 mg or placebo equivalent two times daily. Main Outcome Measures Number-Needed-To-Treat (NNT) and Number-Needed-to-Harm (NNH). NNT was calculated using number of individuals with improvement as indicated by Clinical Global Impressions – Global Improvement scale. NNH was calculated using 3 definitions of adverse outcome: number of participants with GI indicating worsening, number of participants with serious adverse events, and number of participants with adverse events. Results Based on clinician ratings, for every 6 patients treated with amantadine, 1 patient more than placebo would be expected to improve. More participants in the placebo group worsened than in the amantadine group. For every 27 patients treated, 1 more than the placebo would be expected to experience serious adverse events. More participants in the placebo group experienced adverse events of any severity than in the amantadine group. Conclusions Clinician ratings suggest moderate benefit with low risk to appropriately selected patients. Thus, amantadine should be considered a treatment option for the experienced brain injury clinician. These data may support treatment decisions when a pharmaceutical agent is being considered to control irritability/aggression. Author(s) Disclosures Dr. Hammond serves on the Avanir Scientific Advisory Committee.