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.
Similar content being viewed by others
References
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.
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.
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.
Rademaker M. Adverse effects of isotretinoin: a retrospective review of 1743 patients started on isotretinoin. Australas J Dermatol. 2010;51(4):248–53.
McLane J. Analysis of common side effects of isotretinoin. J Am Acad Dermatol. 2001;45(5):S188–94.
Millan SB, Flowers FP, Sherertz EF. Isotretinoin. South Med J. 1987;80(4):494–9.
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.
Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162–9.
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.
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.
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.
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.
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.
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.
Nevoralová Z, Dvořáková D. Mood changes, depression and suicide risk during isotretinoin treatment: a prospective study. Int J Dermatol. 2013;52(2):163–8.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Baum C. Isotretinoin and pregnancy. J Am Acad Dermatol. 1984;10(5 Pt 1):851–4.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brelsford M, Beute TC. Preventing and managing the side effects of isotretinoin. Semin Cutan Med Surg. 2008;27(3):197–206.
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.
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.
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.
Lilley JS, Linton MF, Fazio S. Oral retinoids and plasma lipids. Dermatol Ther. 2013;26(5):404–10.
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.
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.
Hanson N, Leachman S. Safety issues in isotretinoin therapy. Semin Cutan Med Surg. 2001;20(3):166–83.
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.
The effect of omega-3 fatty acid on triglyceride levels in patients using isotretinoin. J Am Acad Dermatol. 2012;66(4):AB19.
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.
Marsden JR. Effect of dietary fish oil on hyperlipidaemia due to isotretinoin and etretinate. Hum Exp Toxicol. 1987;6(3):219–22.
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.
Marson JW, Baldwin HE. New concepts, concerns, and creations in acne. Dermatol Clin. 2019;37(1):1–9.
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.
Kaminsky A. Less common methods to treat acne. Dermatology. 2003;206(1):68–73.
Grando LR, Leite OG, Cestari TF. Pseudo-acne fulminans associated with oral isotretinoin. An Bras Dermatol. 2014;89(4):657–9.
Layton AM, Cunliffe WJ. Guidelines for optimal use of isotretinoin in acne. J Am Acad Dermatol. 1992;27(6 Pt 2):S2–7.
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.
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.
Rademaker M. Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris. Int J Dermatol. 2016;55(5):518–23.
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.
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.
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.
Kaymak Y, Illter N. The effectiveness of intermittent isotretinoin treatment in mild or moderate acne. J Eur Acad Dermatol Venereol. 2006;20:1256–60.
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.
Sardana K, Garg V. Efficacy of low-dose isotretinoin in acne vulgaris. Indian J Dermatol Venereol Leprol. 2010;76:7–13.
Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006;54(4):644–6.
Kumar A, Kumar VK. Toxicity of low-dose intermittent isotretinoin in recalcitrant acne. Med J Armed Forces India. 2010;66(3):208–12.
Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162–9.
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.
Sharma J, Thiboutot DM, Zaenglein AL. The effects of isotretinoin on wisdom tooth extraction. J Am Acad Dermatol. 2012;67(4):794–5.
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.
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.
White GM, Chen W, Yao J, Wolde-Tsadik G. Recurrence rates after the first course of isotretinoin. Arch Dermatol. 1998;134(3):376–8.
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.
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.
Chivot M, Midoun H. Isotretinoin and acne—a study of relapses. Dermatology. 1990;180:240–3.
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.
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.
Fortson MR, Freedman SN, Webster PD 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol. 1995;90(12):2134–9.
Roenigk HH. Liver toxicity of retinoid therapy. J Am Acad Dermatol. 1988;19(1 Pt 2):199–208.
Wolverton S. Comprehensive dermatologic drug therapy. 3rd ed. Saunders; 2012.
Rademaker M, Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us? Australas J Dermatol. 2013;54(3):157–62.
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.
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.
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.
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.
Owen CE. Treating acne with high-dose isotretinoin. JAMA. 2014;311(20):2121.
Author information
Authors and Affiliations
Corresponding author
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
About this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40257-020-00508-0