JAMA Netw Open. 2026 Mar 2;9(3):e261317. doi: 10.1001/jamanetworkopen.2026.1317.
ABSTRACT
IMPORTANCE: Mild traumatic brain injuries (mTBI) involving anxiety and mood, cognitive, migraine and headache, ocular, vestibular, sleep, and autonomic domains can result in chronic symptoms and impairments, thereby increasing morbidity and decreasing quality of life for patients. Timely interventions targeting involved mTBI domains may improve symptoms and impairments and accelerate recovery.
OBJECTIVE: To evaluate the effectiveness of a targeted multidomain (T-MD) intervention for mTBI in adults.
DESIGN, SETTING, AND PARTICIPANTS: This multisite randomized clinical trial (RCT), conducted at 2 specialty concussion clinics from June 2021 to April 2024, involved a 4-week intervention and a total follow-up duration of 3 months. Participants were aged 18 to 49 years and were within 8 days to 6 months of an mTBI.
INTERVENTION: Patients were randomized to T-MD interventions tailored to each domain or a behavioral management control group (control).
MAIN OUTCOMES AND MEASURES: Primary outcomes included changes in the Neurobehavioral Symptom Inventory (NSI) and Patient Global Impression of Change (PGIC) assessed from baseline to 4 weeks. Secondary outcomes included domain-specific symptoms and impairments and adverse events. Least-squares adjusted mean differences (aMDs) and 95% CIs were calculated to assess differences between groups.
RESULTS: Of 1639 patients screened, 745 were eligible and 162 (81 per group) were randomized to T-MD or control (102 female [63%]; 60 male [37%]; mean [SD] age, 29 [8] years). The 2 groups experienced similar improvements over time in NSI symptom severity (aMD, -0.5; 95% CI, -3.6 to 2.6; P = .98) and perceived improvement on the PGIC (odds ratio, 1.18; 95% CI, 0.46-3.04; P = .21). In sensitivity analyses, the T-MD group experienced greater improvement in total (aMD, -4.0; 95% CI, -7.6 to -0.5; P = .045), ocular (aMD, -0.9; 95% CI, -1.7 to -0.1; P = .02), and vestibular (aMD, -0.8; 95% CI, -1.5 to -0.2; P = .01) symptoms; vestibular and ocular motor convergence (aMD, -1.8; 95% CI, -3.2 to -0.3; P = .046); horizontal vestibulo-ocular reflex (aMD, -1.8; 95% CI, -3.2 to -0.3; P = .02); vertical vestibulo-ocular reflex (aMD, -2.2; 95% CI, -3.8 to -0.7; P = .01); visual motion sensitivity (aMD, -2.2; 95% CI, -4.0 to -0.7; P = .01); and cognitive processing speed (aMD, 2.4; 95% CI, 0.6 to 4.2; P = .04). Adverse events were reported by 10 participants (6%).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, mTBI symptoms and patients’ perception of change improved similarly for the T-MD and control groups. These findings can inform a more effective, efficient, and evidence-based approach to care for mTBI.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04549532.
PMID:41817527 | DOI:10.1001/jamanetworkopen.2026.1317
