Carbamazepine for Irritability and Aggression after Traumatic Brain Injury: A Randomized, Placebo-Controlled Study

Abstract

<h3>Research Objectives</h3> To test the hypothesis that carbamazepine (CBZ) reduces irritability/aggression among individuals > 6 months post-traumatic brain injury (TBI). <h3>Design</h3> Parallel-group, randomized, double-blind, placebo-controlled, forced-titration trial of CBZ versus placebo. <h3>Setting</h3> Outpatient. <h3>Participants</h3> 70 individuals with chronic TBI and irritability (CBZ n=35 versus placebo n=35). <h3>Interventions</h3> CBZ (titrated up to 400 mg twice daily) or placebo equivalent two times daily. <h3>Main Outcome Measures</h3> A composite measure of Neuropsychiatric Inventory Irritability and Aggression Domains (NPI-I/A). Global impression of change recorded from participant, observer, and study clinician. <h3>Results</h3> The CBZ group did not differ significantly from the placebo group (p=0.60 and 0.59 for NPI-I/A observer and participant ratings respectively). High placebo effects were observed with Minimal Clinically Important Difference in observer NPI-I/A 57% in CBZ group and 77% in placebo group (p=0.09). Findings were similar for participant ratings. 18 of 35 had therapeutic CBZ level > 4. Therapeutic sample analysis revealed similar high placebo response and non-significant differences except clinician ratings favoring CBZ. Non-serious adverse events occurred more frequently in the CBZ group with greater nervous system effects. <h3>Conclusions</h3> up to 400 mg two times daily was not superior to placebo at reducing irritability/aggression according observers and participants. Large placebo effects may have masked the detection of differences. Clinician rating metrics suggest benefit, and thus, CBZ should remain a treatment option for the experienced brain injury clinician; data are provided that may aid treatment decisions. <h3>Author(s) Disclosures</h3> Dr. Hammond serves on the Avanir Scientific Advisory Committee.