Clinical Efficacy, Adherence, and Real-World Outcomes of Vasovagal Syncope Treatments in Adolescents and Young Adults

BACKGROUND: Vasovagal syncope (VVS) in adolescents and young adults (AYA) is managed with lifestyle, physical counterpressure, compression, and pharmacological strategies, but trials in this population are scarce. This review aimed to assess the efficacy of interventions and the design quality of the supporting evidence. METHODS: Exploratory searches of PubMed/MEDLINE and Google Scholar with verified AI-assisted identification were conducted June 10-August 1, 2026. A search of PubMed/MEDLINE and CENTRAL was performed on August 28, 2026. Primary included studies enrolled pediatric, adolescent, or young adult populations overlapping the 10–30-year range; adult-predominant trials were retained as indirect evidence only when no AYA-specific evidence was available for that intervention. Designs included randomized trials, cohorts, systematic reviews, and meta-analyses that reported recurrence, hemodynamic, quality of life, or adherence outcomes. One reviewer screened and extracted data; narrative synthesis emphasized primary randomized intentionto- treat analyses over secondary, exploratory, per-protocol, retrospective, and subgroup findings. Of the 26 sources identified (21 exploratory; 5 verification), 21 were synthesized (11 primary included studies; 10 indirect, adult-predominant sources), comprising 7 randomized trials (including 2 crossover studies), 5 systematic reviews or meta-analyses, and 9 observational studies; guidelines, narrative reviews, and reference material (18 references) provided background only. RESULTS: Increased salt and water intake reduced pediatric tilt-test positive conversion rates, a surrogate endpoint, and was associated with lower syncope or presyncope recurrence in a subset of pediatric trials. In adult-predominant trials (indirect evidence), physical counterpressure maneuvers could terminate imminent fainting when the prodrome was recognized. Compression garments had no significant effect on 12-month recurrence in an adult-predominant randomized trial, and 37% of participants discontinued treatment (35% with sham stockings). POST 2 (indirect evidence) did not demonstrate a significant primary intention-totreat benefit; the exploratory low-baseline-systolic-pressure hazard ratio of 0.48 represented subgroup evidence. Pediatric cohorts identified exploratory associations between CGRP, serum uric acid, and midodrine response. CONCLUSIONS: Findings are consistent with a guideline-based stepwise approach, but AYA-relevant pediatric evidence is limited to small pediatric trials and observational cohorts, age-specific AYA estimates are generally unavailable, and most randomized evidence is indirect, derived from adult-predominant populations. CGRP, serum uric acid, micronutrients, and baseline systolic pressure are not validated treatment selection criteria. The Autonomic Vulnerability Loop remains a hypothesis-generating model requiring prospective analysis.