Assessing the benefits and risks of amantadine for irritability and aggression after traumatic brain injury

Objective: To quantify the benefits versus harms of amantadine in the treatment of irritability and aggression following traumatic brain injury. Methods: Secondary outcome data from a randomized controlled multisite trial of amantadine 100 mg twice daily were used to calculate number-needed-to-treat (NNT). Given prior findings of positive clinician-perceived effects and low incidence of adverse events, we hypothesized low number-needed-to-treat for benefit (NNTB; high benefit) and high number-needed-to-treat for harm (NNTH; low risk) based on the clinician ratings, supporting the use of amantadine in clinical practice. Specifically, NNTB values were calculated using number of individuals with improvement on the Clinician Global Impressions–Global Improvement scale (GI). NNTH values were computed using number of individuals with worsening on the GI and experiencing serious and any adverse events. Results: Based on clinician ratings, on average for every six patients treated with amantadine rather than placebo, one extra patient would be expected to improve (NNTB = 6.4; 95% confidence interval [CI]: [3.3–76.8]). More participants in the placebo group worsened than in the amantadine group, but the result was not statistically significant (NNTH = −92.4; 95% CI: [NNTB −32.9 to infinity to NNTH −19.2]). The amantadine and placebo groups did not differ on the numbers of adverse events experienced during the trial. Conclusion: Clinician ratings suggest modest benefit of amantadine 100 mg twice daily with low risk to appropriately selected patients with adequate renal clearance. 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.