AUTHOR=Abu-Zaid Ahmed , AlBdah Hoor Ahmad , AlKandari Latifa , Aljuma Retaj S. , Alhussaini Shaikha T. H. , Alqallaf Hawraa Yaqoub , Alsaleeli Fai M. , Alhusaini Rashed Ahmed Soud , Alrasheedi Danah S. , Alshammari Jumanah Abdulrahman , Ashkanani Ali , Alharran Abdullah M. TITLE=Efficacy and safety of oral ivermectin versus benzyl benzoate for the treatment of scabies: a systematic review and meta-analysis of randomized controlled trials JOURNAL=Frontiers in Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1703912 DOI=10.3389/fmed.2025.1703912 ISSN=2296-858X ABSTRACT=Background/objectivesOral ivermectin and topical benzyl benzoate are two common treatment options for scabies, but there is ongoing discussion regarding their relative safety and efficacy. A thorough synthesis of the available evidence is required to inform treatment decisions because of the clinical debate caused by the contradictory findings from current randomized controlled trials (RCTs).MethodsA systematic review and meta-analysis were conducted on evidence retrieved from PubMed, Scopus, Web of Science, and CENTRAL for RCTs up to August 2025. The primary outcome was the cure rate. Secondary outcomes included pruritus improvement and the incidence of adverse events. Stata MP v. 18 was used to pool outcomes.ResultsTen RCTs involving 1,105 patients were included. Cure rates showed no significant difference between ivermectin and benzyl benzoate at 1 week (RR: 1.07, 95% CI [0.88, 1.30], p = 0.51), 2–4 weeks (RR: 0.99, 95% CI [0.88, 1.12], p = 0.91), or after more than 4 weeks (RR: 1.16, 95% CI [0.95, 1.43], p = 0.15). The overall pooled result confirmed no difference (RR: 1.04, 95% CI [0.95, 1.14], p = 0.37). For pruritus, no significant differences were observed at 1 week (RR: 1.07, 95% CI [0.80, 1.43], p = 0.66), 2–4 weeks (RR: 1.19, 95% CI [0.97, 1.46], p = 0.09), or beyond 4 weeks (RR: 1.10, 95% CI [0.89, 1.37], p = 0.38); overall RR: 1.13, 95% CI [0.99, 1.29], p = 0.07. Ivermectin showed significantly fewer adverse events (RR: 0.27, 95% CI [0.16, 0.46], p < 0.001), particularly less burning/stinging (RR: 0.07, 95% CI [0.02, 0.20], p < 0.001). Gastrointestinal (GI) events were not significantly different (RR: 1.47, 95% CI [0.67, 3.22], p = 0.34).ConclusionOral ivermectin and topical benzyl benzoate exhibit comparable efficacy for the treatment of scabies. However, ivermectin’s significantly better safety and tolerability, combined with the practical advantage of oral administration, establish it as a valuable and often preferable therapeutic choice.Systematic review registrationCRD420251143937.