From the Guidelines
For severe traumatic brain injury to the lateral orbitofrontal region with inappropriate behavior, amantadine is generally the best first-line medication choice. Amantadine, typically started at 100mg once or twice daily and potentially increased to 200mg twice daily as tolerated, has shown the most consistent evidence for improving neurobehavioral symptoms and accelerating functional recovery after traumatic brain injury 1. The medication works by enhancing dopaminergic neurotransmission and has NMDA receptor antagonist properties, which helps address the frontal lobe dysfunction that often manifests as disinhibition and inappropriate behavior. Amantadine typically requires 1-2 weeks to show initial effects, and treatment may continue for several months with regular reassessment. Side effects to monitor include insomnia, agitation, hallucinations, and peripheral edema.
While SSRIs like escitalopram may help with emotional regulation, benzodiazepines like clonazepam should generally be avoided as they can impair recovery and worsen cognitive function 1. Progesterone, despite some promising early research, has not shown consistent benefits in clinical trials for traumatic brain injury and is not currently recommended as standard treatment. The management of severe traumatic brain injury patients should prioritize controlling ventilation, maintaining adequate blood pressure, and monitoring for secondary brain insults 1.
Key considerations in the management of severe traumatic brain injury include:
- Assessing the severity of the injury using the Glasgow coma scale and pupillary size and reactivity 1
- Controlling ventilation and maintaining adequate blood pressure 1
- Monitoring for secondary brain insults and managing raised intracranial pressure 1
- Considering the use of amantadine for neurobehavioral symptoms and functional recovery 1
- Avoiding the use of benzodiazepines like clonazepam due to their potential to impair recovery and worsen cognitive function 1.
From the Research
Medication Options for Severe Traumatic Brain Injury
- The best choice of medication for severe traumatic brain injury to the lateral orbitofrontal region in a patient who exhibits inappropriate behavior is not explicitly stated in the provided studies.
- However, the studies suggest that:
- EsCitalopram may be considered for treating major depression following traumatic brain injury, as shown in the study 2.
- Amantadine can be considered for scheduled treatment of agitation and/or aggression in patients with TBI, as recommended in the systematic review 3.
- Clonazepam is a benzodiazepine, which is recommended to be avoided for treating agitation and/or aggression in the context of TBI, according to the systematic review 3.
- Progesterone is not mentioned in the provided studies as a treatment option for severe traumatic brain injury or inappropriate behavior.
Rationale for Medication Choices
- The study 2 found that citalopram treatment for major depression following traumatic brain injury resulted in a response rate of 27.7% and a remission rate of 24.1% at 6 weeks.
- The systematic review 3 recommends avoiding benzodiazepines and haloperidol for treating agitation and/or aggression in TBI patients, and suggests considering atypical antipsychotics, amantadine, β-blockers, antiepileptics, and methylphenidate as alternative treatment options.
- The studies 4 and 5 provide information on the role of the orbitofrontal cortex in cognition and behavior, and the morphological changes in the orbitofrontal cortex following mild traumatic brain injury, but do not provide direct evidence for the treatment of severe traumatic brain injury or inappropriate behavior.
- The study 6 provides a comprehensive review of the current best practice in clinical management and long-term outcomes of moderate to severe TBI, but does not specifically address the treatment of inappropriate behavior.