BACKGROUND: To optimize strategies for achieving the effectiveness of interdisciplinary interventions, this study conducted a comprehensive literature review of all randomized controlled trials (RCT) in adults with traumatic brain injury (TBI) over the past 30 years. METHOD: Three major databases including Medline, PsycINFO and CINAHL were searched, yielding 1176 peer reviewed publications. One hundred RCTs were included, encompassing 55 pharmacologic and non-pharmacologic acute phase trials and 45 rehabilitation and pharmacologic post-acute trials. RESULTS: The majority of acute phase pharmacologic or non-pharmacologic trials (40/55) showed either no effect or adverse effect on TBI outcomes. Several trials involving early nutritional therapy or pre-hospital rapid intubation demonstrated significant treatment effects. The effect of decompressive craniectomy, therapeutic hypothermia and osmotic therapy remained controversial. The majority of post-acute phase trials (36/45), consisting of cognitive rehabilitation, physical rehabilitation and pharmacotherapy, produced various beneficial treatment effects. CONCLUSION: The data indicate that several active interventions during the acute phase of TBI are likely to be more effective than pharmacotherapy, whereas a comprehensive rehabilitation approach is preferred in post-acute phase TBI management. Great progress has been made in understanding the heterogeneous injury mechanisms as well as the complexity of medical management and rehabilitation following the recovery course of TBI.

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A brief summary and a critical assessment of this review may be available at DARE