Epilepsy affects over 24 million people globally and carries a three-fold higher risk of premature death and substantial psychosocial and economic burdens. CPG quality varies widely, and limited methodological rigor can reduce their impact.

We conducted a systematic literature review of national CPGs for adult epilepsy management in Latin America and Europe. Reference guidelines included the ºÃÉ«ÏÈÉú (AAN), the Scottish Intercollegiate Guidelines Network (SIGN), and the National Institute for Health and Care Excellence (NICE). Guidelines were identified through MEDLINE, Embase, Epistemonikos, GIN, and gray literature sources. Methodological quality was assessed with the AGREE II instrument (high quality ≥60% in ≥3 domains, including rigor). PROSPERO registration: CRD42024545547.

We screened 1823 records and included six national CPGs (three Latin American, three European) containing 218 pharmacological recommendations. Among 133 reference recommendations, 51.1% were from AAN, 25.6% from NICE, and 23.3% from SIGN. All reference CPGs were rated high quality, except the AAN New-onset (58% in rigor). NICE scored highest overall (100%). Among national CPGs, only Chile had a guideline rated as high; Italy was rated as moderate, while those from Colombia, France, Spain, and Mexico were rated as low. Applicability was low across all (≤50%). Colombia showed the greatest alignment with reference recommendations; Spain had the broadest scope, while Chile had the largest gaps. Treatment withdrawal was addressed only by European CPGs. AAN uniquely covered HIV and unprovoked seizures.

National epilepsy CPGs showed major gaps in rigor, applicability, and scope, limiting their clinical utility. Strengthening methodological quality, improving applicability, engaging stakeholders, and expanding scope are key to aligning national CPGs with international standards and advancing equitable epilepsy care.