Pharmacologic treatment of cognitive and behavioral sequelae of traumatic brain injury: practicing in the absence of strong evidence.

Cognitive and behavioral sequelae of traumatic brain injury (TBI) interfere with the rehabilitation process and are among the most important sources of long-term disability. Many psychoactive drugs that have been studied in other patient populations are widely used to treat these deficits, but rigorous evidence of their efficacy in TBI is lacking. Use of psychoactive medications in the early post-injury period may appear to be clinically effective, because of the confounding effects of natural recovery. Even single subject assessment methods have limited ability to disentangle drug effects from natural recovery in this period because of the rapid pace and variability of recovery, requiring the application of more traditional parallel group controlled designs. However, the prevalent use of unproven psychoactive drugs in clinical practice can promote a culture of intervention that makes enrollment in controlled studies more challenging. For these reasons, we argue that the early use of unproven psychoactive medications after TBI should be limited, that placebo controlled group studies should be encouraged, and that single subject methods can be most productively used in later periods when natural recovery has slowed.