Skip to main content
SpringerLink
Log in

Optimizing Isotretinoin Treatment of Acne: Update on Current Recommendations for Monitoring, Dosing, Safety, Adverse Effects, Compliance, and Outcomes

  • Therapy in Practice
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Acne vulgaris is the most common skin disease treated by dermatologists. It can be severe and result in permanent scars. Isotretinoin is the most effective treatment for acne and has the potential for long-term clearance. Prescribing and monitoring protocols can vary widely among prescribers. Recent studies, reports, and consensus statements help shed light on optimizing the use of isotretinoin for acne. A recent literature review is summarized in this article to help the practitioner optimize isotretinoin use for acne. The article outlines the advantages and disadvantages of standard, high-dose, and low-dose isotretinoin regimens; discusses the current status of controversies surrounding isotretinoin (including depression/suicide, pregnancy, and inflammatory bowel disease); reviews monitoring recommendations and treatment for hypertriglyceridemia and elevated transaminase levels; and discusses common adverse effects seen with isotretinoin, along with their treatment and prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Collier CN, Harper JC, Cantrell WC, Wang W, Foster KW, Elewski BE. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58(1):56–9.

    Article  PubMed  Google Scholar 

  2. Gollnick HP, Bettoli V, Lambert J, Araviiskaia E, Binic I, Dessinioti C, et al. A consensus-based practical and daily guide for the treatment of acne patients. J Eur Acad Dermatol Venereol. 2016;30(9):1480–90.

    Article  CAS  PubMed  Google Scholar 

  3. Greywal T, Zaenglein AL, Baldwin HE, Bhatia N, Chernoff KA, Del Rosso JQ, et al. Evidence-based recommendations for the management of acne fulminans and its variants. J Am Acad Dermatol. 2017;77(1):109–17.

    Article  PubMed  Google Scholar 

  4. Rademaker M. Adverse effects of isotretinoin: a retrospective review of 1743 patients started on isotretinoin. Australas J Dermatol. 2010;51(4):248–53.

    Article  PubMed  Google Scholar 

  5. McLane J. Analysis of common side effects of isotretinoin. J Am Acad Dermatol. 2001;45(5):S188–94.

    Article  CAS  PubMed  Google Scholar 

  6. Millan SB, Flowers FP, Sherertz EF. Isotretinoin. South Med J. 1987;80(4):494–9.

    Article  CAS  PubMed  Google Scholar 

  7. Neudorfer M, Goldshtein I, Shamai-Lubovitz O, Chodick G, Dadon Y, Shalev V. Ocular adverse effects of systemic treatment with isotretinoin. Arch Dermatol. 2012;148(7):803–8.

    Article  CAS  PubMed  Google Scholar 

  8. Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sundström A, Alfredsson L, Sjölin-Forsberg G, Gerdén B, Bergman U, Jokinen J. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ. 2010;341:c5812.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Marqueling AL, Zand LT. Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Semin Cutan Med Surg. 2005;24(2):92–102.

    Article  CAS  PubMed  Google Scholar 

  11. Yang YC, Tu HP, Hong CH, Chang WC, Fu HC, Ho JC, et al. Female gender and acne disease are jointly and independently associated with the risk of major depression and suicide: a national population-based study. Biomed Res Int. 2014;2014:504279.

    PubMed  PubMed Central  Google Scholar 

  12. Halvorsen JA, Stern RS, Dalgard F, Thoresen M, Bjertness E, Lien L. Suicidal ideation, mental health problems, and social impairment are increased in adolescents with acne: a population-based study. J Invest Dermatol. 2011;131(2):363–70.

    Article  CAS  PubMed  Google Scholar 

  13. Rowe C, Spelman L, Oziemski M, Ryan A, Manoharan S, Wilson P, et al. Isotretinoin and mental health in adolescents: Australian consensus. Australas J Dermatol. 2014;55(2):162–7.

    Article  PubMed  Google Scholar 

  14. Jick SS, Kremers HM, Vasilakis-Scaramozza C. Isotretinion use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol. 2000;136(10):1231–6.

    Article  CAS  PubMed  Google Scholar 

  15. Nevoralová Z, Dvořáková D. Mood changes, depression and suicide risk during isotretinoin treatment: a prospective study. Int J Dermatol. 2013;52(2):163–8.

    Article  PubMed  Google Scholar 

  16. Rehn L, Meririnne E, Höök-Nikanne J, Isometsä E, Henriksson M. Depressive symptoms and suicidal ideation during isotretinoin treatment: a 12-week follow-up study of male Finnish military conscripts. J Eur Acad Dermatol Venereol. 2009;23(11):1294–7.

    Article  CAS  PubMed  Google Scholar 

  17. Bozdaǧ KE, Gülseren Ş, Güven F, Çam B. Evaluation of depressive symptoms in acne patients treated with isotretinoin. J Dermatolog Treat. 2009;20(5):293–6.

    Article  PubMed  Google Scholar 

  18. Simić D, Situm M, Letica E, Penavić JZ, Zivković MV, Tomić T. Psychological impact of therapy with isotretinoin in moderate and severe acne patients. Acta Derm Venereol. 2009;33(Suppl 2):15–9.

    Google Scholar 

  19. Suarez B, Serrano A, Cova Y, Baptista T. Isotretinoin was not associated with depression or anxiety: a twelve-week study. World J Psychiatry. 2016;6(1):136–42.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Rubinow DR, Peck GL, Squillace KM, Gantt GG. Reduced anxiety and depression in cystic acne patients after successful treatment with oral isotretinoin. J Am Acad Dermatol. 1987;17(1):25–32.

    Article  CAS  PubMed  Google Scholar 

  21. Hahm BJ, Min SU, Yoon MY, Shin YW, Kim JS, Jung JY, et al. Changes of psychiatric parameters and their relationships by oral isotretinoin in acne patients. J Dermatol. 2009;36(5):255–61.

    Article  CAS  PubMed  Google Scholar 

  22. 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):701–6.

    Article  PubMed  Google Scholar 

  23. Marqueling AL, Zane LT. Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Semin Cutan Med Surg. 2005;24(2):92–102.

    Article  CAS  PubMed  Google Scholar 

  24. Huang YC, Cheng YC. Isotretinoin treatment for acne and risk of depression: a systematic review and meta-analysis. J Am Acad Dermatol. 2017;76(6):1068–1076.e9.

    Article  CAS  PubMed  Google Scholar 

  25. 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):S1–S23.e1.

  26. Baum C. Isotretinoin and pregnancy. J Am Acad Dermatol. 1984;10(5 Pt 1):851–4.

    PubMed  Google Scholar 

  27. Shin J, Cheetham TC, Wong L, Niu F, Kass E, Yoshinaga MA, et al. The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system. J Am Acad Dermatol. 2011;65(6):1117–25.

    Article  CAS  PubMed  Google Scholar 

  28. Collins MK, Moreau JF, Opel D, Swan J, Prevost N, Hastings M, et al. Compliance with pregnancy prevention measures during isotretinoin therapy. J Am Acad Dermatol. 2014;70(1):55–9.

    Article  PubMed  Google Scholar 

  29. Werner CA, Papic MJ, Ferris LK, Lee JK, Borrero S, Prevost N, et al. Women’s experiences with isotretinoin risk reduction counseling. JAMA Dermatology. 2014;150(4):366–71.

    Article  PubMed  Google Scholar 

  30. Crockett SD, Porter CQ, Martin CF, Sandler RS, Kappelman MD. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010;105(9):1986–93.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Dubeau M-F, Iacucci M, Beck PL, Moran GW, Kaplan GG, Ghosh S, et al. Drug-induced inflammatory bowel disease and IBD-like conditions. Inflamm Bowel Dis. 2013;19(2):445–56.

    Article  PubMed  Google Scholar 

  32. Alhusayen RO, Juurlink DN, Mamdani MM, Morrow RL, Shear NH, Dormuth CR. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study. J Invest Dermatol. 2013;133(4):907–12.

    Article  CAS  PubMed  Google Scholar 

  33. Etminan M, Bird ST, Delaney JA, Bressler B, Brophy JM. Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data. JAMA Dermatol. 2013;149(2):216–20.

    Article  PubMed  Google Scholar 

  34. Rashtak S, Khaleghi S, Pittelkow MR, Larson JJ, Lahr BD, Murray JA. Isotretinoin exposure and risk of inflammatory bowel disease. JAMA Dermatology. 2014;150(12):1322.

    Article  PubMed  Google Scholar 

  35. Bernstein CN, Nugent Z, Longobardi T, Blanchard JF. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009;104(11):2774–8.

    Article  CAS  PubMed  Google Scholar 

  36. Hansen TJ, Lucking SM, Miller JJ, Kirby JS, Thiboutot DM, Zaenglein AL. Standardized laboratory monitoring with use of isotretinoin in acne. J Am Acad Dermatol. 2016;75(2):323–8.

    Article  CAS  PubMed  Google Scholar 

  37. Brelsford M, Beute TC. Preventing and managing the side effects of isotretinoin. Semin Cutan Med Surg. 2008;27(3):197–206.

    Article  CAS  PubMed  Google Scholar 

  38. Brzezinski P, Borowska K, Chiriac A, Smigielski J. Adverse effects of isotretinoin: a large, retrospective review. Dermatol Ther. 2017. https://doi.org/10.1111/dth.12483.

    Article  PubMed  Google Scholar 

  39. Rao PK, Bhat RM, Nandakishore B, Dandakeri S, Martis J, Kamath GH. Safety and efficacy of low-dose isotretinoin in the treatment of moderate to severe acne vulgaris. Indian J Dermatol. 2014;59(3):316.

    PubMed  PubMed Central  Google Scholar 

  40. Opel D, Kramer ON, Chevalier M, Bigby M, Albrecht J. Not every patient needs a triglyceride check, but all can get pancreatitis: a systematic review and clinical characterization of isotretinoin-associated pancreatitis. Br J Dermatol. 2017;177(4):960–6.

    Article  CAS  PubMed  Google Scholar 

  41. Lilley JS, Linton MF, Fazio S. Oral retinoids and plasma lipids. Dermatol Ther. 2013;26(5):404–10.

    Article  PubMed  Google Scholar 

  42. Rodondi N, Darioli R, Ramelet AA, Hohl D, Lenain V, Perdrix J, et al. High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study. Ann Intern Med. 2002;136(8):582–9.

    Article  CAS  PubMed  Google Scholar 

  43. Alcalay J, Landau M, Zucker A. Analysis of laboratory data in acne patients treated with isotretinoin: is there really a need to perform routine laboratory tests? J Dermatolog Treat. 2001;12(1):9–12.

    Article  CAS  PubMed  Google Scholar 

  44. Hanson N, Leachman S. Safety issues in isotretinoin therapy. Semin Cutan Med Surg. 2001;20(3):166–83.

    Article  CAS  PubMed  Google Scholar 

  45. Krishna S, Okhovat J-P, Kim J, Kim CN. Influence of ω-3 fatty acids on triglyceride levels in patients using isotretinoin. JAMA Dermatol. 2015;151(1):101.

    Article  PubMed  PubMed Central  Google Scholar 

  46. The effect of omega-3 fatty acid on triglyceride levels in patients using isotretinoin. J Am Acad Dermatol. 2012;66(4):AB19.

  47. Lyons F, Laker MF, Marsden JR, Manuel R, Shuster S. Effect of oral 13-cis-retinoic acid on serum lipids. Br J Dermatol. 1982;107(5):591–5.

    Article  CAS  PubMed  Google Scholar 

  48. Marsden JR. Effect of dietary fish oil on hyperlipidaemia due to isotretinoin and etretinate. Hum Exp Toxicol. 1987;6(3):219–22.

    Article  CAS  Google Scholar 

  49. Webster GF, Webster TG, Grimes LR. Laboratory tests in patients treated with isotretinoin: occurrence of liver and muscle abnormalities and failure of AST and ALT to predict liver abnormality. Dermatol Online J. 2017;23(5):3.

    Google Scholar 

  50. Marson JW, Baldwin HE. New concepts, concerns, and creations in acne. Dermatol Clin. 2019;37(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  51. Hartung B, Merk HF, Huckenbeck W, Daldrup T, Neuen-Jacob E, Ritz-Timme S. Severe generalised rhabdomyolysis with fatal outcome associated with isotretinoin. Int J Legal Med. 2012;126(6):953–6.

    Article  PubMed  Google Scholar 

  52. Kaminsky A. Less common methods to treat acne. Dermatology. 2003;206(1):68–73.

    Article  PubMed  Google Scholar 

  53. Grando LR, Leite OG, Cestari TF. Pseudo-acne fulminans associated with oral isotretinoin. An Bras Dermatol. 2014;89(4):657–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Layton AM, Cunliffe WJ. Guidelines for optimal use of isotretinoin in acne. J Am Acad Dermatol. 1992;27(6 Pt 2):S2–7.

    Article  CAS  PubMed  Google Scholar 

  55. Cunliffe WJ, Van de Kerkhof PCM, Caputo R, Cavicchini S, Cooper A, Fyrand OL, et al. Roaccutane treatment guidelines: results of an international survey. Dermatology. 1997;194(4):351–7.

    Article  CAS  PubMed  Google Scholar 

  56. Tan J, Knezevic S, Boyal S, Waterman B, Janik T. Evaluation of evidence for acne remission with oral isotretinoin cumulative dosing of 120–150 mg/kg. J Cutan Med Surg. 2016;20(1):13–20.

    Article  CAS  PubMed  Google Scholar 

  57. Rademaker M. Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris. Int J Dermatol. 2016;55(5):518–23.

    Article  CAS  PubMed  Google Scholar 

  58. Blasiak RC, Stamey CR, Burkhart CN, Lugo-Somolinos A, Morrell DS. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149(12):1392.

    Article  CAS  PubMed  Google Scholar 

  59. Blasiak RC, Stamey CR, Burkhart CN, Lugo-Somolinos A, Morrell DS. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149(12):1392.

    Article  CAS  PubMed  Google Scholar 

  60. Agarwal US, Besarwal RK, Bhola K. Oral isotretinoin in different dose regimens for acne vulgaris: a randomized comparative trial. Indian J Dermatol Venereol Leprol. 2011;77(6):688–94.

    Article  PubMed  Google Scholar 

  61. Kaymak Y, Illter N. The effectiveness of intermittent isotretinoin treatment in mild or moderate acne. J Eur Acad Dermatol Venereol. 2006;20:1256–60.

    Article  CAS  PubMed  Google Scholar 

  62. Akman A, Durusoy C, Senturk M, Koc CK, Soyturk D, Alpsoy E. Treatment of acne with intermittent and conventional isotretinoin: a randomized, controlled multicenter study. Arch Dermatol Res. 2007;299(10):467–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sardana K, Garg V. Efficacy of low-dose isotretinoin in acne vulgaris. Indian J Dermatol Venereol Leprol. 2010;76:7–13.

    Article  PubMed  Google Scholar 

  64. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006;54(4):644–6.

    Article  PubMed  Google Scholar 

  65. Kumar A, Kumar VK. Toxicity of low-dose intermittent isotretinoin in recalcitrant acne. Med J Armed Forces India. 2010;66(3):208–12.

    Article  CAS  PubMed  Google Scholar 

  66. Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Guadanhim LRS, Gonçalves RG, Bagatin E. Observational retrospective study evaluating the effects of oral isotretinoin in keloids and hypertrophic scars. Int J Dermatol. 2016;55(11):1255–8.

    Article  CAS  PubMed  Google Scholar 

  68. Sharma J, Thiboutot DM, Zaenglein AL. The effects of isotretinoin on wisdom tooth extraction. J Am Acad Dermatol. 2012;67(4):794–5.

    Article  CAS  PubMed  Google Scholar 

  69. Spring LK, Krakowski AC, Alam M, Bhatia A, Brauer J, Cohen J, et al. Isotretinoin and timing of procedural interventions. JAMA Dermatol. 2017;153(8):802.

    Article  PubMed  Google Scholar 

  70. Waldman A, Bolotin D, Arndt KA, Dover JS, Geronemus RG, Chapas A, et al. ASDS Guidelines Task Force. Dermatol Surg. 2017;43(10):1249–62.

    Article  CAS  PubMed  Google Scholar 

  71. White GM, Chen W, Yao J, Wolde-Tsadik G. Recurrence rates after the first course of isotretinoin. Arch Dermatol. 1998;134(3):376–8.

    Article  CAS  PubMed  Google Scholar 

  72. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. Isotretinoin for acne vulgaris—10 years later: a safe and succesful treatment. Br J Dermatol. 1993;108:333–43.

    Google Scholar 

  73. Stainforth JM, Layton AM, Taylor JP, Cunliffe WJ. Isotretinoin for the treatment of acne vulgaris: which factors may predict the need for more than one course? Br J Dermatol. 1993;129(3):297–301.

    Article  CAS  PubMed  Google Scholar 

  74. Chivot M, Midoun H. Isotretinoin and acne—a study of relapses. Dermatology. 1990;180:240–3.

    Article  CAS  Google Scholar 

  75. Truchuelo MT, Jiménez N, Mavura D, Jaén P. Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin. Actas Dermo-Sifiliográficas. 2015;106(2):126–32.

    Article  CAS  PubMed  Google Scholar 

  76. Krishna S, Kim C, Kim J. The effect of omega-3 fatty acid on triglyceride levels in patients using isotretinoin. J Am Acad Dermatol. 2012;66(4 Suppl 1):AB19.

    Google Scholar 

  77. Fortson MR, Freedman SN, Webster PD 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol. 1995;90(12):2134–9.

    CAS  PubMed  Google Scholar 

  78. Roenigk HH. Liver toxicity of retinoid therapy. J Am Acad Dermatol. 1988;19(1 Pt 2):199–208.

    Article  PubMed  Google Scholar 

  79. Wolverton S. Comprehensive dermatologic drug therapy. 3rd ed. Saunders; 2012.

  80. Rademaker M, Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us? Australas J Dermatol. 2013;54(3):157–62.

    Article  PubMed  Google Scholar 

  81. Ahmad HM. Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin. Dermatol Ther. 2015;28(3):151–7.

    Article  PubMed  Google Scholar 

  82. Sardana K, Garg VK, Sehgal VN, Mahajan S, Bhushan P. Efficacy of fixed low-dose isotretinoin (20 mg, alternate days) with topical clindamycin gel in moderately severe acne vulgaris. J Eur Acad Dermatol Venereol. 2009;23(5):556–60.

    Article  CAS  PubMed  Google Scholar 

  83. Mandekou-Lefaki I, Delli F, Teknetzis A, Euthimiadou R, Karakatsanis G. Low-dose schema of isotretinoin in acne vulgaris. Int J Clin Pharmacol Res. 2003;23(2–3):41–6.

    CAS  PubMed  Google Scholar 

  84. Boyraz N, Mustak PK. Comparison of the efficacies of intermittent and continuous low-dose isotretinoin regimens in the treatment of moderate acne vulgaris. Int J Dermatol. 2013;52(10):1265–7.

    CAS  PubMed  Google Scholar 

  85. Owen CE. Treating acne with high-dose isotretinoin. JAMA. 2014;311(20):2121.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine (Dermatology), University of Louisville School of Medicine, Louisville, KY, USA

    Megan N. Landis

  2. The Dermatology and Skin Cancer Center of Southern Indiana, Corydon, IN, USA

    Megan N. Landis

Authors
  1. Megan N. Landis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Megan N. Landis.

Ethics declarations

Funding

No sources of funding were provided for this manuscript.

Conflict of interest

Megan N. Landis has served on advisory boards for Mayne and Janssen, and as an investigator for Galderma, Novartis, Pfizer, and Foamix.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Landis, M.N. Optimizing Isotretinoin Treatment of Acne: Update on Current Recommendations for Monitoring, Dosing, Safety, Adverse Effects, Compliance, and Outcomes. Am J Clin Dermatol 21, 411–419 (2020). https://doi.org/10.1007/s40257-020-00508-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-020-00508-0

Search

Navigation