This study tested the hypothesis that carbamazepine (CBZ) reduces irritability/aggression among individuals >6 months post-traumatic brain injury (TBI). Seventy individuals were enrolled in a parallel-group, randomized, double-blind, placebo-controlled, forced-titration trial of CBZ (n = 35) versus placebo (n = 35). Participants were randomly assigned to receive CBZ or placebo 42 days with outcome assessed at baseline and Day 42. Dose was titrated up to 400 mg CBZ or placebo equivalent two times daily. Symptoms of irritability and aggression were measured using the Neuropsychiatric Inventory Irritability (NPI-I) and Aggression (NPI-A) domains as a composite measure (NPI-I/A). Global impression of change was recorded from participant, observer, and study clinician. 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. Eighteen 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. CBZ 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.
Bibliographical noteFunding Information:
The study was conducted at Carolinas Rehabilitation in Charlotte, NC, a large academic medical center. The study was approved by the local Institutional Review Board and registered on www .clinicaltrials.gov identifier NCT00621751. No important protocol changes were made after the trial commenced. Study conduct adhered to the approved protocol. A safety committee provided independent oversight. The National Institute on Disability Independent Living and Rehabilitation Research provided financial support, including funds to purchase CBZ. Informed consent was obtained from participants and observers. The first author designed the study. All authors vouch for the data and analysis accuracy.
© 2021 Mary Ann Liebert, Inc., publishers.
All Science Journal Classification (ASJC) codes
- Clinical Neurology