Pharmacotherapy to enhance arousal: what is known and what is not

Severe brain injury results in a disturbance among a wide range of critical neurotransmitter systems. Each neurotransmitter system places its own functional role while being interconnected to a multitude of other systems and functions. This chapter seeks to review the major neurotransmitter systems involved after severe acquired brain injury. While limited in their construct, animal models of brain injury have demonstrated agents that may assist in the recovery process and those that may further slow recovery. We review further the issue of laboratory evidence and what is transferable to the clinic. Lastly, this chapter reviews published clinical pharmacotherapy studies or trials in the arena of arousal for those with clinical severe brain injury. We discuss limitations as well as findings and present the available evidence in a table-based format. While no clear evidence exists to suggest a defined and rigid pharmacotherapeutic approach, interesting data does suggest that several medications have been associated with enhanced arousal. Several studies are underway or about to begin that will shed more light on the utility of such agents in improving function after severe brain injury. For now, clinicians must employ their own judgment and what has been learned from the limited literature to the care of a challenging group of persons.