Adjunctive Amantadine Treatment for Aggressive Behavior in Children: A Series of Eight Cases

Purpose: Amantadine has a growing body of evidence for the treatment of aggressive behavior in patients with traumatic brain injury, autism spectrum disorder, and developmental disability. We describe our experience with adjunctive amantadine treatment for aggressive behavior in eight hospitalized children. Methods: We conducted a retrospective chart review of psychiatric inpatients initiated on amantadine for the management of aggressive behavior. Results: The majority of patients were male (n = 7) ranging in age from 6 to 10 years (mean 8.5). The most common diagnoses were attention-deficit/hyperactivity disorder (n = 6), intermittent explosive disorder (n = 4), oppositional defiant disorder (n = 4), and bipolar disorder (n = 3). Five patients had either borderline intellectual functioning or an unspecified cognitive disorder, and four patients had either confirmed or suspected in utero substance exposure. Included patients received amantadine for a minimum of 20 days. Mean adjunctive amantadine starting dose was 2.6 mg/(kg·day) and mean discharge dose was 6.7 mg/(kg·day). The treating child and adolescent psychiatrist described five patients as very much improved and three patients as much improved following amantadine therapy. Average seclusions and PRN medications per week were reduced from baseline to week 1 of amantadine (1.81, 95% CI [1.02, 2.61] versus 0.25, 95% CI [0.00, 0.55] (p = 0.01) and 4, 95% CI [2.22, 5.78] versus 1.63, 95% CI [0.71, 2.54] (p = 0.02)), respectively. Both physical restraints and seclusions were reduced from baseline in the second week of amantadine (1.56, 95% CI [0.45, 2.68] versus 0.00, 95% CI [0.00, 0.00] [p = 0.04] and 1.81, 95% CI [1.02, 2.61] versus 0.13, 95% CI [0.00, 0.35] [p = 0.01]), respectively. No adverse events related to amantadine were identified. Conclusions: We describe clinical improvement supported by objective measures in eight children with aggressive behavior treated with adjunctive amantadine. These findings warrant further investigation as patients were taking other mood stabilizing medications and there are limitations associated with retrospective chart reviews.