Buspirone and Brain Injury

SIR: Severe traumatic brain injury can result in dementia, epilepsy, and behavioral disturbances, including impulsivity, agitation, and aggression. These behaviors may reflect injury to the orbitofrontal region of the brain, an area vulnerable to traumatic events. Although numerous medications for behavioral disturbances exist, none have shown consistent efficacy. I report on the effective treatment of severe traumatic brain injury with behavioral disturbance using buspirone and discuss a possible mechanism.

The patient, a 45-year-old man who sustained a closed head injury from an unhelmeted motorcycle accident, was stabilized following initial coma. Head CT showed bilateral frontal contusions. A behavioral syndrome developed that was marked by spontaneous yelling, cursing, and assaultive behavior. He required help with daily activities and was unable to engage in meaningful conversation or undergo formal neuropsychological evaluation. He received numerous psychopharmacological trials, adequate in dose and length of treatment, including high- and low-potency antipsychotics, mood stabilizers, anticonvulsants, antidepressants, beta-blockers, and sedatives. Limited positive response to some medications was noted in the first few days to weeks or when he became sedated; otherwise, they did not result in a sustained positive outcome. On presentation 8 years after injury, he scored in the severe range on a clinical dementia rating scale. He was treated with buspirone 60 mg orally per day over a 4-month period. All behavioral symptoms described above ameliorated. He used physical therapy and became more independent in caring for himself. He engaged in brief conversation, such as “I feel fine” or “the weather is bad,” although he was still unable to undergo formal neuropsychological evaluation.

Buspirone is potentially effective in treating aggression associated with mental retardation¹ and dementia.² Buspirone's actions on 5-HT_1A serotonin receptors may induce long-term changes in central serotonergic neurotransmission.³ Dysfunction in serotonin metabolism correlates with disturbances in aggression regulation.⁴ The major site of serotonergic cell bodies is the raphe nuclei of the midbrain, an area that projects widely to the basal ganglia, the limbic system, and the cortex. Efficacy of buspirone in this and other cases implicates a role for the 5-HT_1A receptor system in the treatment of some forms of aggression associated with brain injury, and possibly in their pathophysiology as well.