Epilepsy-related stigma (ERS) continues to be a significant challenge affecting people with epilepsy (PWE) worldwide and is closely associated with reduced quality of life and poor treatment adherence. Although various anti-ERS interventions have been developed, the effectiveness of personalized approaches has not been systematically evaluated. This systematic review synthesizes the available evidence on personalized anti-ERS interventions in epilepsy, focusing on their effectiveness as a strategy to reduce ERS. We systematically searched for studies evaluating personalized interventions aimed at ERS, including internalized, perceived, enacted, and courtesy stigma, and examined their effects on related psychosocial outcomes. We coded interventions across four personalization domains: age, culture, clinical/condition-specific factors, and setting. Of the 1,454 records screened, 74 studies from 34 countries were included, comprising 45 studies that directly evaluated the effectiveness of personalized anti-ERS interventions and 29 that indirectly assessed their potential impact on ERS through related psychological or quality of life outcomes. Overall, 78.4% (58/74) of interventions reported favorable outcomes, with favorable outcomes reported for 94.3% (33/35) of highly personalized interventions, compared with 73.1% (19/26) of moderately personalized and 46.2% (6/13) of low/basic personalization interventions. Few interventions targeted adolescents and transitional-age youth, and most studies were conducted in high-income countries. This study suggests an association between greater personalization and more favorable intervention outcomes. Personalized, collaboratively developed, culturally relevant, and developmentally tailored strategies are needed, particularly for adolescents and in low- and middle-income countries, alongside future research integrating standardized outcomes, long-term follow-up, and structural approaches to achieve sustainable stigma reduction.
