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Review Articles

Isotretinoin for acne vulgaris – an update on adverse effects and laboratory monitoring

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Pages 2414-2424 | Received 10 Jul 2021, Accepted 08 Aug 2021, Published online: 23 Mar 2022

References

  • Rademaker M. Adverse effects of isotretinoin: a retrospective review of 1743 patients started on isotretinoin. Australas J Dermatol. 2010;51(4):248–253.
  • Burney W, Bosanac SS, Nguyen C, et al. Short-term exposure of human sebocytes to 13-cis-retinoic acid induces acnegenic changes. Br J Dermatol. 2018;179(5):1201–1202.
  • Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162–169.
  • Clark SM, Cunliffe WJ. Acne flare and isotretinoin – incidence and treatment. Br J Dermatol. 1995;133(45):26.
  • Borghi A, Mantovani L, Minghetti S, et al. Acute acne flare following isotretinoin administration: potential protective role of low starting dose. Dermatology. 2009;218(2):178–180.
  • Wysowski DK, Pitts M, Beitz J. Depression and suicide in patients treated with isotretinoin. N Engl J Med. 2001;344(6):460.
  • Bachmann C, Grabarkiewicz J, Theisen FM, et al. Isotretinoin, depression and suicide ideation in an adolescent boy. Pharmacopsychiatry. 2007;40(3):128.
  • O’Reilly K, Bailey SJ, Lane MA. Retinoid-mediated regulation of mood: possible cellular mechanisms. Exp Biol Med. 2008;233(3):251–258.
  • Halvorsen JA, Stern RS, Dalgard F, et al. Suicidal ideation, mental health problems, and social impairment are increased in adolescents with acne: a population-based study. J Invest Dermatol. 2011;131(2):363–370.
  • Yazici K, Baz K, Yazici A, et al. Disease-specific quality of life is associated with anxiety and depression in patients with acne. J Eur Acad Dermatol Venereol. 2004;18(4):435–439.
  • Vallerand IA, Lewinson RT, Parsons LM, et al. Risk of depression among patients with acne in the U.K.: a population-based cohort study. Br J Dermatol. 2018;178(3):e194–e195.
  • Aktan S, Ozmen E, Berna S, Anxiety, depression, and nature of acne vulgaris in adolescents. Int J Dermatol. 2000;39(5):354–357.
  • Azoulay L, Sc M, Blais L, et al. Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study. J Clin Psychiatry. 2008;69(4):526–532.
  • Thakrar BT, Robinson NJ. Isotretinoin and the risk of depression. J Clin Psychiatry. 2009;70(10):1475.
  • Sundström A, Alfredsson L, Sjölin-Forsberg G, et al. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ. 2010;341(7782):c5812.
  • Droitcourt C, Nowak E, Rault C, et al. Risk of suicide attempt associated with isotretinoin: a nationwide cohort and nested case-time-control study. Int J Epidemiol. 2019;48(5):1623–1635.
  • Bozdağ KE, Gülseren Ş, Güven F, et al. Evaluation of depressive symptoms in acne patients treated with isotretinoin. J Dermatolog Treat. 2009;20(5):293–296.
  • Metekoglu S, Oral E, Ucar C, et al. Does isotretinoin cause depression and anxiety in acne patients? Dermatol Ther. 2019;32(2):3–6.
  • Rehn L, E M, Höök-Nikanne J, et al. Depressive symptoms and suicidal ideation during isotretinoin treatment: a 12-week follow-up study of male Finnish military conscripts. J Euro Acad Dermatol Venereol. 2009;23(11):1294–1297.
  • Nevoralová Z, Dvořáková D. Mood changes, depression and suicide risk during isotretinoin treatment: a prospective study. Int J Dermatol. 2013;52(2):163–168.
  • Marron SE, Tomas-Aragones L, Boira S. Anxiety, depression, quality of life and patient satisfaction in acne patients treated with oral isotretinoin. Acta Derm Venerol. 2013;93(6):701–706.
  • Kaymak Y, Taner E, Taner Y. Comparison of depression, anxiety and life quality in acne vulgaris patients who were treated with either isotretinoin or topical agents. Int J Dermatol. 2009;48(1):41–46.
  • Ng CH, Tam MM, Celi E, et al. Prospective study of depressive symptoms and quality of life in acne vulgaris patients treated with isotretinoin compared to antibiotic and topical therapy. Australas J Dermatol. 2002;43(4):262–268.
  • Cohen J, Adams S, Patten S. No association found between patients receiving isotretinoin for acne and the development of depression in a Canadian prospective cohort. Can J Clin Pharmacol. 2007;14(2):227–233.
  • Suarez B, Serrano A, Cova Y, et al. Isotretinoin was not associated with depression or anxiety: a twelve-week study. World J Psychiatry. 2016;6(1):136–142.
  • McGrath EJ, Lovell CR, Gillison F, et al. A prospective trial of the effects of isotretinoin on quality of life and depressive symptoms. Br J Dermatol. 2010;163(6):1323–1329.
  • Erdoğan Y, Erturan İ, Aktepe E, et al. Comparison of quality of life, depression, anxiety, suicide, social anxiety and obsessive-compulsive symptoms between adolescents with acne receiving isotretinoin and antibiotics: a prospective, non-randomised, open-label study. Paediatr Drugs. 2019;21(3):195–202.
  • 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.
  • Li C, Chen J, Wang W, et al. Use of isotretinoin and risk of depression in patients with acne: a systematic review and meta-analysis. BMJ Open. 2019;9(1):e021549.
  • Crockett SD, Porter CQ, Martin CF, et al. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010;105(9):1986–1993.
  • Etminan M, Bird ST, Delaney JA, et al. 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):216–220.
  • Margolis DJ, Fanelli M, Hoffstad O, et al. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010;105(12):2610–2616.
  • Lee TW, Russell L, Deng M, et al. Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad. Intern Med J. 2013;43(8):919–926.
  • Becker E, Schmidt TSB, Bengs S, et al. Effects of oral antibiotics and isotretinoin on the murine gut microbiota. Int J Antimicrob Agents. 2017;50(3):342–351.
  • Crockett SD, Gulati A, Sandler RS, et al. A causal association between isotretinoin and inflammatory bowel disease has yet to be established. Am J Gastroenterol. 2009;104(10):2387–2393.
  • Racine A, Cuerq A, Bijon A, et al. Isotretinoin and risk of inflammatory bowel disease: a French nationwide study. Am J Gastroenterol. 2014;109(4):563–569.
  • Rashtak S, Khaleghi S, Pittelkow MR, et al. Isotretinoin exposure and risk of inflammatory bowel disease. JAMA Dermatol. 2014;150(12):1322–1326.
  • Alhusayen RO, Juurlink DN, Mamdani MM, et al. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study. J Invest Dermatol. 2013;133(4):907–912.
  • Wright S, Strunk A, Garg A. Risk of new-onset inflammatory bowel disease among patients with acne vulgaris exposed to isotretinoin. J Am Acad Dermatol. 2021;84(1):41–45.
  • Lee SY, Jamal MM, Nguyen ET, et al. Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. Eur J Gastroenterol Hepatol. 2016;28(2):210–216.
  • Coughlin SS. Clarifying the purported association between isotretinoin and inflammatory bowel disease. J Environ Heal Sci. 2015;1(2):1–5.
  • Godfrey KM, James MP. Treatment of severe acne with isotretinoin in patients with inflammatory bowel disease. Br J Dermatol. 1990;123(5):653–655.
  • Schleicher SM. Oral isotretinoin and inflammatory bowel disease. J Am Acad Dermatol. 1985;13(5):834–835.
  • Mejer J, Dierckls G, Pas H. Is isotretinoin safe in patients with acne and inflammatory bowel disease? J Invest Dermatol. 2018;138(5):S71.
  • Fraunfelder FW, Fraunfelder FT, Corbett JJ. Isotretinoin-associated intracranial hypertension. Ophthalmology. 2004;111(6):1248–1250.
  • Kadam P, Whitfeld M. Isotretinoin and doxycyline use in treating acneiform eruption following chemotherapy. Australas J Dermatol. 2018;59(S1):76.
  • Friedman DI. Medication-induced intracranial hypertension in dermatology. Am J Clin Dermatol. 2005;6(1):29–37.
  • Tintle SJ, Harper JC, Webster GF, et al. Safe use of therapeutic-dose oral isotretinoin in patients with a history of pseudotumor cerebri. JAMA Dermatol. 2016;152(5):582–584.
  • Fraunfelder FT, Fraunfelder FW, Edwards R. Ocular side effects possibly associated with isotretinoin usage. Am J Ophthalmol. 2001;132(3):299–305.
  • Neudorfer M, Goldshtein I, Shamai-Lubovitz O, et al. Ocular adverse effects of systemic treatment with isotretinoin. Arch Dermatol. 2012;148(7):803–808.
  • Maclean H, Wright M, Choi D, et al. Abnormal night vision with isotretinoin therapy for acne. Clin Exp Dermatol. 1995;20(1):86.
  • Mollan SP, Woodcock M, Siddiqi R, et al. Does use of isotretinoin rule out a career in flying? Br J Ophthalmol. 2006;90(8):957–959.
  • Brown RD, Grattan CEH. Visual toxicity of synthetic retinoids. Br J Ophthalmol. 1989;73(4):286–288.
  • Grattan CEH, Brown RD, Cowan MA, et al. Retinoids and the eye - reduced rod function with isotretinoin. Br J Dermatol. 1987;117(s32):23.
  • Weleber RG, Denman ST, Hanifin JM, et al. Abnormal retinal function associated with isotretinoin therapy for acne. Arch Ophthalmol. 1986;104(6):831–837.
  • Law WC, Rando RR. The molecular basis of retinoic acid induced night blindness. Biochem Biophys Res Commun. 1989;161(2):825–829.
  • Ellis CN, Pennes DR, Hermann RC, et al. Long-term radiographic follow-up after isotretinoin therapy. J Am Acad Dermatol. 1988;18(6):1252–1261.
  • Ellis CN, Madison KC, Pennes DR, et al. Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol. 1984;10(6):1024–1029.
  • Kilcoyne RF, Cope R, Cunningham W, et al. Minimal spinal hyperostosis with low-dose isotretinoin therapy. Invest Radiol. 1986;21(1):41–44.
  • Pennes DR, Ellis CN, Madison KC, et al. Early skeletal hyperostoses secondary to 13-cis-retinoic acid. AJR Am J Roentgenol. 1984;142(5):979–983.
  • Mader R, Verlaan J-J, Buskila D. Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nat Rev Rheumatol. 2013;9(12):741–750.
  • Weinfeld RM, Olson PN, Maki DD, et al. The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in two large american midwest metropolitan hospital populations. Skeletal Radiol. 1997;26(4):222–225.
  • Gerber LH, Helfgott RK, Gross EG, et al. Vertebral abnormalities associated with synthetic retinoid use. J Am Acad Dermatol. 1984;10(5):817–823.
  • Carey BM, Parkin GJ, Cunliffe WJ, et al. Skeletal toxicity with isotretinoin therapy: a clinico-radiological evaluation. Br J Dermatol. 1988;119(5):609–614.
  • Tangrea JA, Kilcoyne RF, Taylor PR, et al. Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin. Arch Dermatol. 1992;128(7):921–925.
  • Milstone LM, McGuire J, Ablow RC. Premature epiphyseal closure in a child receiving oral 13-cis-retinoic acid. J Am Acad Dermatol. 1982;7(5):663–666.
  • Marini JC, Hill S, Zasloff MA. Dense metaphyseal bands and growth arrest associated with isotretinoin therapy. Am J Dis Child. 1988;142(3):316–318.
  • Steele RG, Lugg P, Richardson M. Premature epiphyseal closure secondary to single-course vitamin a therapy. Aust N Z J Surg. 1999;69(11):825–827.
  • Tran A, Walker J, Shulakewych M. Premature epiphyseal closure in pediatric patients on isotretinoin therapy. J Am Acad Dermatol. 2008;58(2):AB7.
  • Luthi F, Eggel Y, Theumann N. Premature epiphyseal closure in an adolescent treated by retinoids for acne: an unusual cause of anterior knee pain. Joint Bone Spine. 2012;79(3):314–316.
  • Standeven AM, Davies PJA, Chandraratna RAS, et al. Retinoid-induced epiphyseal plate closure in guinea pigs. Fundam Appl Toxicol. 1996;34(1):91–98.
  • Chroni E, Monastirli A, Tsambaos D. Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians. Drug Saf. 2010;33(1):25–34.
  • Landau M, Mesterman R, Ophir J, et al. Clinical significance of markedly elevated serum creatine kinase levels in patients with acne on isotretinoin. Acta Derm Venereol. 2001;81(5):350–352.
  • Hartung B, Merk HF, Huckenbeck W, et al. Severe generalised rhabdomyolysis with fatal outcome associated with isotretinoin. Int J Legal Med. 2012;126(6):953–956.
  • Kaymak Y. Creatine phosphokinase values during isotretinoin treatment for acne. Int J Dermatol. 2008;47(4):398–401.
  • Melnik BC. Overexpression of p53 explains isotretinoin’s teratogenicity. Exp Dermatol. 2018;27(1):91–93.
  • Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med. 1985;313(14):837–841.
  • Dai WS, LaBraico JM, Stern RS. Epidemiology of isotretinoin exposure during pregnancy. J Am Acad Dermatol. 1992;26(4):599–606.
  • Koren G. Retinoic acid embryopathy. N Engl J Med. 1986;315(4):262.
  • Stern RS, Rosa F, Baum C. Isotretinoin and pregnancy. J Am Acad Dermatol. 1984;10(5):851–854.
  • iPLEDGE 2019 [cited 2019 Aug 25]. Available from: www.ipledgeprogram.com/
  • Department of Health Australian Government. Poisons Standard February 2019 2019 [cited 2019 Feb 10]. Available from: https://www.legislation.gov.au/Details/F2019L00032
  • Kovitwanichkanont T, Driscoll T. A comparative review of the isotretinoin pregnancy risk management programs across four continents. Int J Dermatol. 2018;57(9):1035–1046.
  • World Helath Organization. Vitamin A supplementation during pregnancy 2020 [cited 2020 Jan 7]. Available from: https://www.who.int/elena/titles/guidance_summaries/vitamina_pregnancy/en/
  • Çinar L, Kartal D, Ergin C, et al. The effect of systemic isotretinoin on male fertility. Cutan Ocul Toxicol. 2016;35(4):296–299.
  • Amory JK, Ostrowski KA, Gannon JR, et al. Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study. Andrology. 2017;5(6):1115–1123.
  • Cinar SL, Kartal D, Aksoy H, et al. Long-term effect of systemic isotretinoin on female fertility. Cutan Ocul Toxicol. 2017;36(2):132–134.
  • Coleman R, MacDonald D. Effects of isotretinoin on male reproductive system. Lancet. 1994;344(8916):198.
  • Isotretinoin (Roaccutane®) and erectile dysfunction 2015 [cited 2018 Dec 7]. Available from: https://www.lareb.nl/en/news/isotretinoin-roaccutane-and-erectile-dysfunction/
  • Rademaker M, Wallace M, Cunliffe W, et al. Isotretinoin treatment alters steroid metabolism in women with acne. Br J Dermatol. 1991;124(4):361–364.
  • Lee YH, Scharnitz TP, Muscat J, et al. Laboratory monitoring during isotretinoin therapy for acne: a systematic review and meta-analysis. JAMA Dermatol. 2016;152(1):35–44.
  • Hansen TJ, Lucking SM, Miller JJ, et al. Standardized laboratory monitoring with use of isotretinoin in acne. J Am Acad Dermatol. 2016;75(2):323–328.
  • Öktem A, Hayran Y, Arı E, et al. Minimize the regular laboratory monitoring during the systemic isotretinoin treatment: data of 704 patients with acne vulgaris. J Dermatolog Treat. 2019;30(8):813–817.
  • Barbieri JS, Shin DB, Wang S, et al. 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.
  • Zane LT, Leyden WA, Marqueling AL, et al. A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris. Arch Dermatol. 2006;142(8):1016–1022.
  • 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):1–4.
  • DeKlotz CMC, Roby KD, Friedlander SF. Dietary supplements, isotretinoin, and liver toxicity in adolescents: a retrospective case series. Pediatrics. 2017;140(4):e20152940.
  • Opel D, Kramer ON, Chevalier M, et al. 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):960–966.
  • Fallah H, Rademaker M. Isotretinoin in the management of acne vulgaris: practical prescribing. Int J Dermatol. 2021;60(4):451–460.
  • Luvizotto PP, Schmitt JV. Depressive symptoms before and during treatment of acne with isotretinoin and its correlations: a prospective study. An Bras Dermatol. 2020;95(6):760–770.
  • Bray AP, Kravvas G, Skevington SM, et al. Is there an association between isotretinoin therapy and adverse mood changes? A prospective study in a cohort of acne patients. J Dermatolog Treat. 2019;30(8):796–801.
  • Gnanaraj P, Karthikeyan S, Narasimhan M, et al. Decrease in “Hamilton rating scale for depression” following isotretinoin therapy in acne: an open-label prospective study. Indian J Dermatol. 2015;60(5):461–464.
  • Fakour Y, Noormohammadpour P, Ameri H, et al. The effect of isotretinoin (roaccutane) therapy on depression and quality of life of patients with severe acne. Iran J Psychiatry. 2014;9(4):237–240.
  • Yesilova Y, Bez Y, Ari M, et al. Effects of isotretinoin on obsessive compulsive symptoms, depression, and anxiety in patients with acne vulgaris. J Dermatolog Treat. 2012;23(4):268–271.
  • Ergun T, Seckin D, Ozaydin N, et al. Isotretinoin has no negative effect on attention, executive function and mood. J Eur Acad Dermatol Venereol. 2012;26(4):431–439.
  • Hahm BJ, Min SU, Yoon MY, et al. Changes of psychiatric parameters and their relationships by oral isotretinoin in acne patients. J Dermatol. 2009;36(5):255–261.
  • Kaymak Y, Kalay M, Ilter N, et al. Incidence of depression related to isotretinoin treatment in 100 acne vulgaris patients. Psychol Rep. 2006;99(3):897–906.
  • Chia CY, Lane W, Chibnall J, et al. Isotretinoin therapy and mood changes in adolescents with moderate to severe acne: a cohort study. Arch Dermatol. 2005;141(5):557–560.
  • Ferahbas A, Turan MT, Esel E, et al. A pilot study evaluating anxiety and depressive scores in acne patients treated with isotretinoin. J Dermatolog Treat. 2004;15(3):153–157.
  • Bernstein CN, Nugent Z, Longobardi T, et al. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009;104(11):2774–2778.

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