{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:56Z","timestamp":1792788596225,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The optimal isotretinoin dosing strategy for acne vulgaris remains debated, balancing efficacy against dose-dependent toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the efficacy, safety, and post-treatment outcomes of low-dose (\u22640.5\u202fmg\/kg\/day) versus conventional-dose (0.5\u20131.0\u202fmg\/kg\/day) isotretinoin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase, CENTRAL, and Web of Science for randomized controlled trials (RCTs). The primary outcome was the change in Global Acne Grading System (GAGS) score at 24\u202fweeks. Secondary outcomes included post-treatment worsening quantified as GAGS score deterioration, adverse events, and patient satisfaction. Certainty of evidence was assessed using GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four trials (210 randomized; 202 analyzed) were included. At 24\u202fweeks, the pooled mean difference favored neither regimen [MD\u202f=\u202f\u22121.87, 95% CI (\u22124.38, 0.64);\n                      <jats:italic>p\u202f=<\/jats:italic>\n                      0.15;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f85.67%]. Heterogeneity was predominantly attributable to one trial that enrolled more severe cases and used adjunctive antibiotics\/corticosteroids; excluding it reduced heterogeneity and maintained no significant difference under a random-effects model [MD\u202f=\u202f\u22120.92, 95% CI (\u22122.62, 0.77);\n                      <jats:italic>p\u202f=<\/jats:italic>\n                      0.28;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f44.97%]. Post-treatment worsening did not differ overall and, in sensitivity analyses excluding the co-intervention trial, showed no statistically significant difference with no heterogeneity [MD\u202f=\u202f0.10, 95% CI (\u22121.67, 1.86);\n                      <jats:italic>p\u202f=<\/jats:italic>\n                      0.91;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f0%]. Low-dose regimens had higher patient satisfaction [SMD\u202f=\u202f0.99, 95% CI (0.63, 1.34);\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001] and better tolerability. Certainty of evidence was low for efficacy and moderate for safety and satisfaction (GRADE).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In RCTs conducted predominantly in moderate acne and in contexts minimizing co-interventions, low-dose isotretinoin provides comparable 24-week efficacy to conventional dosing while offering superior tolerability and higher patient satisfaction. Conventional dosing may yield a modestly faster early response; however, the absolute differences were small and evidence in substantially more severe acne remains limited and context-dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      Registered in PROSPERO (ID: CRD42024536322), URL:\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD42024536322<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1771320","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:22:52Z","timestamp":1773033772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Individualizing isotretinoin dosing in acne: comparable 24-week efficacy and better tolerability at lower daily doses"],"prefix":"10.3389","volume":"13","author":[{"given":"Jingmin","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S0140-6736(11)60321-8","article-title":"Acne vulgaris","volume":"379","author":"Williams","year":"2012","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1001\/jama.2021.17633","article-title":"Management of acne vulgaris: a review","volume":"326","author":"Eichenfield","year":"2021","journal-title":"JAMA"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/bjd.13749","article-title":"Psychological impact of acne on 21st-century adolescents: decoding for better care","volume":"172","author":"Revol","year":"2015","journal-title":"Br J Dermatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1111\/bjd.21739","article-title":"A systematic review and network meta-analysis of topical pharmacological, oral pharmacological, physical and combined treatments for acne vulgaris","volume":"187","author":"Mavranezouli","year":"2022","journal-title":"Br J Dermatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/bjd.17981","article-title":"Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis","volume":"181","author":"Clayton","year":"2019","journal-title":"Br J Dermatol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1007\/s13555-021-00552-6","article-title":"Updated treatment for acne: targeted therapy based on pathogenesis","volume":"11","author":"Kurokawa","year":"2021","journal-title":"Dermatol 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in acne vulgaris","volume":"55","author":"Rademaker","year":"2016","journal-title":"Int J Dermatol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1046\/j.1365-2133.2003.05209_1.x","article-title":"Two new adverse effects of isotretinoin","volume":"148","author":"Charalabopoulos","year":"2003","journal-title":"Br J Dermatol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s40257-015-0127-7","article-title":"Adverse effects of acne medications: recognition and management","volume":"16","author":"Oudenhoven","year":"2015","journal-title":"Am J Clin Dermatol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.2147\/DDDT.S427530","article-title":"Oral isotretinoin and its uses in dermatology: a review","volume":"17","author":"Paichitrojjana","year":"2023","journal-title":"Drug Des Devel Ther"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1111\/j.1365-2133.2011.10440.x","article-title":"Low-dose isotretinoin in acne vulgaris: a critical review","volume":"165","author":"Sardana","year":"2011","journal-title":"Br J Dermatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1111\/jdv.12170","article-title":"Isotretinoin 5\u202fmg daily for low- grade adult acne vulgaris-a placebo-controlled, randomized double-blind study","volume":"28","author":"Rademaker","year":"2014","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"554","DOI":"10.53350\/pjmhs20221612554","article-title":"Analyzing the effects of low-dose isotretinoin on acne vulgaris against the standard treatment protocol","volume":"16","author":"Jabbar","year":"2022","journal-title":"Pak J Med Health 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Literature review by the European Academy of Dermatology and Venereology Task Force on quality of life and patient oriented outcomes","volume":"32","author":"Chernyshov","year":"2018","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"CD009435","DOI":"10.1002\/14651858.CD009435.pub2","article-title":"Oral isotretinoin for acne","volume":"11","author":"Costa","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1111\/j.1365-2133.2010.10152.x","article-title":"Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study","volume":"164","author":"Lee","year":"2011","journal-title":"Br J Dermatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e15974","DOI":"10.1111\/dth.15974","article-title":"Evaluation of the efficacy and relapse rates of treatment protocols for moderate acne using isotretinoin based on the global acne grading system: randomized, controlled, comparative study","volume":"35","author":"Kassem","year":"2022","journal-title":"Dermatol Ther"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e12715","DOI":"10.1111\/dth.12715","article-title":"The effect of continuous high versus low dose oral isotretinoin regimens on dermcidin expression in patients with moderate to severe acne vulgaris","volume":"31","author":"El Aziz Ragab","year":"2018","journal-title":"Dermatol Ther"},{"key":"ref27","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions","author":"Higgins","year":"2024"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4103\/jrpp.JRPP_17_30","article-title":"Comparing the efficacy of low dose and conventional dose of oral isotretinoin in treatment of moderate and severe acne vulgaris","volume":"6","author":"Faghihi","year":"2017","journal-title":"J Res Pharm Pract"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e13251","DOI":"10.1111\/dth.13251","article-title":"Low dose of isotretinoin: a comprehensive review","volume":"33","author":"Abdelmaksoud","year":"2020","journal-title":"Dermatol Ther"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1177\/1203475415595776","article-title":"Evaluation of evidence for acne remission with oral isotretinoin cumulative dosing of 120\u2013150\u202fmg\/kg","volume":"20","author":"Tan","year":"2016","journal-title":"J Cutan Med Surg"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/j.1440-0960.2012.00947.x","article-title":"Isotretinoin: dose, duration and relapse. What does 30\u202fyears of usage tell us?","volume":"54","author":"Rademaker","year":"2013","journal-title":"Australas J Dermatol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1771320\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:22:53Z","timestamp":1773033773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1771320\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":31,"alternative-id":["10.3389\/fmed.2026.1771320"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1771320","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]},"article-number":"1771320"}}