Impact of pharmacological treatments on cognitive and behavioral outcome in the postacute stages of adult traumatic brain injury: a meta-analysis.

Pharmacological treatments that are administered to adults in the postacute stage after a traumatic brain injury (TBI) (≥4 weeks after injury) have the potential to reduce persistent cognitive and behavioral problems. While a variety of treatments have been examined, the findings have yet to be consolidated, hampering advances in the treatment of TBI. A meta-analysis of research that has investigated the cognitive and behavioral effects of pharmacological treatments administered in the later stage after TBI was therefore conducted. The PubMed and PsycINFO databases were searched, and Cohen d effect sizes, percent overlap, and failsafe N statistics were calculated for each treatment. Both randomized controlled trials and open-label studies (prospective and retrospective) were included. Nineteen treatments were investigated by 30 independent studies, comprising 395 participants with TBI in the treatment groups and 137 control subjects. When treated in the postacute period, 1 dopaminergic agent (methylphenidate) improved behavior (anger/aggression, psychosocial function) and 1 cholinergic agent (donepezil) improved cognition (memory, attention). In addition, when the injury-to-treatment interval was broadened to include studies that administered treatment just before the postacute period, 2 dopaminergic agents (methylphenidate, amantadine) showed clinically useful treatment benefits for behavior, whereas 1 serotonergic agent (sertraline) markedly impaired cognition and psychomotor speed.