Isotretinoin: Facts and contradictions
https://doi.org/10.21518/ms2025-357
Abstract
Acne is one of the most common skin diseases that leads to persistent stigmatization and negatively affects the quality of life of patients. Currently, there are many treatments for this disease, but isotretinoin is the most effective against severe forms of acne and those cases where other forms of therapy have failed. Isotretinoin is an oral retinoid used in clinical practice for about 40 years. This drug affects all the key links in the pathogenesis of acne, which determines its high effectiveness. Many clinical studies have been devoted to the study of the mechanisms of action of this drug, the specifics of its purpose, and undesirable side effects. However, today, both patients and doctors have a number of misconceptions about the use of this drug, which raises concerns about its administration, errors in treatment tactics and low adherence to treatment. This article discusses the main issues about the mechanisms of action of isotretinoin, the specifics of its administration, indications and contraindications for use, undesirable side effects and ways to correct them, as well as the contradictions in the tactics of prescribing this drug that prevent its effective use. Special attention is paid to choosing the optimal therapeutic dose of isotretinoin and the duration of the course of treatment. In addition, the article discusses the main factors leading to failures in systemic retinoid therapy: slowing the onset of clinical response, the development of relapses after treatment, among which are the features of the course of the disease, the age of the patient, his hormonal background, as well as the dosage of the drug and the duration of its administration.
About the Author
E. V. Dvoriankova
Center for Theoretical Problems of Physical and Chemical Pharmacology of Russian Academy of Sciences
Russian Federation
Russian Federation
Evgeniya V. Dvoriankova - Dr. Sci. (Med.), Chief Researcher Laboratory of Physical, Chemical and Genetic Problems of Dermatology.
30, Srednyaya Kalitnikovskaya St., Moscow, 109029
References
1. Vallerand IA, Lewinson RT, Farris MS, Sibley CD, Ramien ML, Bulloch AGM, Patten SB. Efficacy and adverse events of oral isotretinoin for acne: a systematic review. Br J Dermatol. 2018;178(1):76–85. https://doi.org/10.1111/bjd.15668.
2. Chernyshov PV, Tomas-Aragones L, Manolache L, Svensson A, Marron SE, Evers AWM et al. Which acne treatment has the best influence on healthrelated quality of life? Literature review by the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes. J Eur Acad Dermatol Venereol. 2018;32(9):1410–1419. https://doi.org/10.1111/jdv.15048.
3. Costa CS, Bagatin E, Martimbianco ALC, da Silva EM, Lúcio MM, Magin P, Riera R. Oral isotretinoin for acne. Cochrane Database Syst Rev. 2018;11(11):CD009435. https://doi.org/10.1002/14651858.CD009435.pub2.
4. Gollnick H, Ehlert R, Rinck G, Orfanos CE. Retinoids: an overview of pharmacokinetics and therapeutic value. Methods Enzymol. 1990;190:291–304. https://doi.org/10.1016/0076-6879(90)90034-x.
5. Colburn WA, Gibson DM, Wiens RE, Hanigan JJ. Food increases the bioavailability of isotretinoin. J Clin Pharmacol. 1983;23(11-12):534–539. https://doi.org/10.1002/j.1552-4604.1983.tb01800.x.
6. Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, 4-treatment, crossover study. J Am Acad Dermatol. 2013;69(5):762–767. https://doi.org/10.1016/j.jaad.2013.05.036.
7. Wiegand UW, Chou RC. Pharmacokinetics of oral isotretinoin. J Am Acad Dermatol. 1998;39(2 Pt 3):S8–S12. https://doi.org/10.1016/s01909622(98)70438-4.
8. Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol. 2006;126(10):2178–2189. https://doi.org/10.1038/sj.jid.5700289.
9. Shi G, Liao PY, Cai XL, Pi XX, Zhang MF, Li SJ et al. FoxO1 enhances differentiation and apoptosis in human primary keratinocytes. Exp Dermatol. 2018;27(11):1254–1260. https://doi.org/10.1111/exd.13775.
10. Rademaker M. Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris. Int J Dermatol. 2016;55(5):518–523. https://doi.org/10.1111/ijd.12942.
11. Norris DA, Osborn R, Robinson W, Tonnesen MG. Isotretinoin produces significant inhibition of monocyte and neutrophil chemotaxis in vivo in patients with cystic acne. J Invest Dermatol. 1987;89(1):38–43. https://doi.org/10.1111/1523-1747.ep12580370.
12. Papakonstantinou E, Aletras AJ, Glass E, Tsogas P, Dionyssopoulos A, Adjaye J et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol. 2005;125(4):673–684. https://doi.org/10.1111/j.0022-202X.2005.23848.x.
13. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945–973. https://doi.org/10.1016/j.jaad.2015.12.037.
14. Altman EM. Isotretinoin and pregnancy prevention: do we need to take a long, hard look at ourselves? JAMA Dermatol. 2014;150(4):361–362. https://doi.org/10.1001/jamadermatol.2013.6973.
15. Spierings NM, Natkunarajah J, Bansal A, Ostlere L. Should we be prescribing isotretinoin to patients with peanut allergies. Clin Exp Dermatol. 2015;40(7):824–825. https://doi.org/10.1111/ced.12750.
16. Pierret L, Grosber M, Gutermuth J. Is isotretinoin treatment safe in patients with known peanut allergy? J Eur Acad Dermatol Venereol. 2016;30(1):140–141. https://doi.org/10.1111/jdv.12630.
17. Hulstaert E, Van Autryve E, Temmerman L. Is isotretinoin treatment safe in patients with known peanut allergy? Reply. J Eur Acad Dermatol Venereol. 2016;30(2):376. https://doi.org/10.1111/jdv.12807.
18. Jones H, Blanc D, Cunliffe WJ. 13-cis retinoic acid and acne. Lancet. 1980;2(8203):1048–1049. https://doi.org/10.1016/s0140-6736(80)92273-4.
19. Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskaia E, Barona Cabal MI et al. Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2018;78(2 Suppl 1):S1–S23.e1. https://doi.org/10.1016/j.jaad.2017.09.078.
20. Borghi A, Mantovani L, Minghetti S, Giari S, Virgili A, Bettoli V. Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in achieving stable remission. J Eur Acad Dermatol Venereol. 2011;25(9):1094–1098. https://doi.org/10.1111/j.1468-3083.2010.03933.x.
21. De D, Kanwar AJ. Combination of low-dose isotretinoin and pulsed oral azithromycin in the management of moderate to severe acne: a preliminary open-label, prospective, non-comparative, single-centre study. Clin Drug Investig. 2011;31(8):599–604. https://doi.org/10.2165/11539570000000000-00000.
22. Ballanger F, Baudry P, N’Guyen JM, Khammari A, Dréno B. Heredity: a prognostic factor for acne. Dermatology. 2006;212(2):145–149. https://doi.org/10.1159/000090655.
23. Rademaker M, Wishart JM, Birchall NM. Isotretinoin 5 mg daily for lowgrade adult acne vulgaris – a placebo-controlled, randomized doubleblind study. J Eur Acad Dermatol Venereol. 2014;28(6):747–754. https://doi.org/10.1111/jdv.12170.
24. Sakaniya LR, Mildzikhova DR, Piruzyan AL, Korsunskaya IM. Therapy strategy for moderate to severe acne. Klinicheskaya Dermatologiya i Venerologiya. 2022;21(3):400–403. (In Russ.) https://doi.org/10.17116/klinderma202221031400.
25. Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3): 162–169. https://doi.org/10.4161/derm.1.3.9364.
26. Quéreux G, Volteau C, N’Guyen JM, Dréno B. Prospective study of risk factors of relapse after treatment of acne with oral isotretinoin. Dermatology. 2006;212(2):168–176. https://doi.org/10.1159/000090658.
27. Moradi Tuchayi S, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC. Acne vulgaris. Nat Rev Dis Primers. 2015;1:15029. https://doi.org/10.1038/nrdp.2015.29.
28. Cakir GA, Erdogan FG, Gurler A. Isotretinoin treatment in nodulocystic acne with and without polycystic ovary syndrome: efficacy and determinants of relapse. Int J Dermatol. 2013;52(3):371–376. https://doi.org/10.1111/j.1365-4632.2012.05691.x.
29. Bagatin E, Costa CS. The use of isotretinoin for acne – an update on optimal dosing, surveillance, and adverse effects. Expert Rev Clin Pharmacol. 2020;13(8):885–897. https://doi.org/10.1080/17512433.2020.1796637.
30. Fallah H, Rademaker M. Isotretinoin in the management of acne vulgaris: practical prescribing. Int J Dermatol. 2021;60(4):451–460. https://doi.org/10.1111/ijd.15089.
31. Borghi A, Mantovani L, Minghetti S, Virgili A, Bettoli V. Acute acne flare following isotretinoin administration: potential protective role of low starting dose. Dermatology. 2009;218(2):178–180. https://doi.org/10.1159/000182270.
32. Barbieri JS, Shin DB, Wang S, Margolis DJ, Takeshita J. The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time. J Am Acad Dermatol. 2020;82(1):72–79. https://doi.org/10.1016/j.jaad.2019.06.025.
33. Lee YH, Scharnitz TP, Muscat J, Chen A, Gupta-Elera G, Kirby JS. Laboratory Monitoring During Isotretinoin Therapy for Acne: A Systematic Review and Meta-analysis. JAMA Dermatol. 2016;152(1):35–44. https://doi.org/10.1001/jamadermatol.2015.3091.
34. Marron SE, Tomas-Aragones L, Boira S. Anxiety, depression, quality of life and patient satisfaction in acne patients treated with oral isotretinoin. Acta Derm Venereol. 2013;93(6):701–706. https://doi.org/10.2340/00015555-1638.
35. Jick SS, Kremers HM, Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol. 2000;136(10):1231–1236. https://doi.org/10.1001/archderm.136.10.1231.
36. Ault A. Isotretinoin use may be linked with depression. Lancet. 1998;351(9104):730. https://doi.org/10.1016/S0140-6736(05)78502-0.
37. Dvoriankova EV, Shevchenko NA, Zhukova OV. Psychiatric comorbidity and psycho-emotional status of patients with acne. Meditsinskiy Sovet. 2022;(13):38–46. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-13-38-46.
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For citations:
Dvoriankova EV. Isotretinoin: Facts and contradictions. Meditsinskiy sovet = Medical Council. 2025;(14):8-14. (In Russ.) https://doi.org/10.21518/ms2025-357
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