To present an evidence-based review of randomized controlled trials (RCTs) evaluating interventions for the management of behavioral issues post moderate to severe traumatic brain injury (MSTBI), as part of an extensive database that has been conceptualized as a living systematic review. Systematic searches were conducted in MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO, up to and including December 2022, for articles published in the English language, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of RCT was assessed using the Physiotherapy Evidence Database (PEDro) scale, and level of evidence was assigned using a modified Sackett scale. Forty-six RCTs examining interventions and outcome measures related to behavioral issues post-MSTBI were included. These studies collectively enrolled 3,267 participants. The majority of RCTs were conducted in the United States (n=27; 58.7%) and 28 (60.9%) were conducted after 2010. Of these, 27 RCTs examined non-pharmacological interventions and 19 examined pharmacological interventions. Effective pharmacological treatments included amantadine and dexmedetomidine. Effective non-pharmacological interventions included sensory stimulation in the acute phase, anger self-management programs, peer mentoring, problem-solving, and emotional regulation. Psychotherapy showed conflicting evidence. This evidence-based review provides a comprehensive overview of the research landscape of RCTs addressing behavior post-MSTBI. The findings from these RCTs may be valuable for health care professionals, researchers, and policymakers involved in the field of TBI and behavior.
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