Assistant Professor Indiana University School of Medicine Indianapolis, Indiana
Research Objectives: To test the hypothesis that carbamazepine (CBZ) reduces irritability/aggression among individuals > 6 months post-traumatic brain injury (TBI).
Design: Parallel-group, randomized, double-blind, placebo-controlled, forced-titration trial of CBZ versus placebo.
Participants: 70 individuals with chronic TBI and irritability (CBZ n=35 versus placebo n=35).
Interventions: CBZ (titrated up to 400 mg twice daily) or placebo equivalent two times daily.
Main Outcome Measures: A composite measure of Neuropsychiatric Inventory Irritability and Aggression Domains (NPI-I/A). Global impression of change recorded from participant, observer, and study clinician.
Results: 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.
Conclusions: 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.
Author(s) Disclosures: Dr. Hammond serves on the Avanir Scientific Advisory Committee.
Upon completion, participants will be able to describe the findings of the first randomized, placebo-controlled trial of carbamazepine for TBI irritability and aggression.
Upon completion, participants will be able to discuss the expected benefit and harm of carbamazepine treatment for irritability and aggression.
Upon completion, participants will be able to discuss the issue of placebo effect in rehabilitation clinical trials.