Skip to main content
SpringerLink
Log in

Important Controversies Associated with Isotretinoin Therapy for Acne

  • Current Opinion
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris. Soon after the drug’s release in the early 1980s, a number of important adverse effects were reported subsequently leading to a variety of medical and medicolegal controversies. Three of these controversies will be highlighted concerning the putative role of isotretinoin in (1) depression and suicide, (2) inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It appears that a very small subset of patients receiving isotretinoin for acne are at risk for depression, which is very manageable provided there is adequate patient awareness of the possibility, maximum communication between the patient and physician, and cessation of therapy if clinically important depression occurs (after which the depression rapidly resolves in a week or less). Multiple controlled studies actually suggest a very favorable effect of isotretinoin on depression and anxiety common in the population requiring isotretinoin. With regard to inflammatory bowel disease, in just one study, only ulcerative colitis association with isotretinoin reached statistical significance. The actual incidence of this association is strikingly low. Finally, it is clear that even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris.

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

Similar content being viewed by others

References

  1. Scheinman PL, Peck GL, Rubinow DR, et al. Acute depression from isotretinoin. J Am Acad Dermatol. 1990;22(6 Pt 1):1112–4.

    Article  PubMed  CAS  Google Scholar 

  2. Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol. 2001;45(4):515–9.

    Article  PubMed  CAS  Google Scholar 

  3. Hull PR, D’Arcy C. Isotretinoin use and subsequent depression and suicide: presenting the evidence. Am J Clin Dermatol. 2003;4(7):493–505.

    Article  PubMed  Google Scholar 

  4. McGrath EJ, Lovell CR, Gillison F. A prospective trial of the effects of isotretinoin on quality of life and depressive symptoms. Br J Dermatol. 2010;163(6):1323–9.

    Article  PubMed  CAS  Google Scholar 

  5. Bozdag KE, Gulseren S, Guven F, et al. Evaluation of depressive symptoms in acne patients treated with isotretinoin. J Dermatol Treat. 2009;20(5):293–6.

    Article  Google Scholar 

  6. Rehn LM, Meririnne E, Hook-Nikanne J, et al. 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  PubMed  CAS  Google Scholar 

  7. 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):41–6.

    Article  PubMed  CAS  Google Scholar 

  8. 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):255–61.

    Article  PubMed  CAS  Google Scholar 

  9. Kellett SC, Gawkrodger DJ. A prospective study of the responsiveness of depression and suicidal ideation in acne patients to different phases of isotretinoin therapy. Eur J Dermatol. 2005;15(6):484–8.

    PubMed  CAS  Google Scholar 

  10. Ferahbas A, Turan MT, Esel E, et al. A pilot study evaluating anxiety and depressive scores in acne patients treated with isotretinoin. J Dermatol Treat. 2004;15(3):153–7.

    Article  CAS  Google Scholar 

  11. Kellett SC, Gawkrodger DJ. The psychological and emotional impact of acne and the effect of treatment with isotretinoin. Br J Dermatol. 1999;140(2):273–82.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. 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):e227–33.

    PubMed  Google Scholar 

  14. 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):557–60.

    Article  PubMed  CAS  Google Scholar 

  15. 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):262–8.

    Article  PubMed  Google Scholar 

  16. Hersom K, Neary MP, Levaux HP, et al. Isotretinoin and antidepressant pharmacotherapy: a prescription sequence symmetry analysis. J Am Acad Dermatol. 2003;49(3):424–32.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Sundstrom A, Alfredsson L, Sjolin-Forsberg G, et al. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ. 2010;341:c5812.

    Article  PubMed  Google Scholar 

  19. Azoulay L, Blais L, Koren G, et al. Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study. J Clin Psych. 2008;69(4):526–32.

    Article  CAS  Google Scholar 

  20. Schleicher SM. Oral isotretinoin and inflammatory bowel disease. J Am Acad Dermatol. 1985;13(5 Pt 1):834–5.

    Article  PubMed  CAS  Google Scholar 

  21. 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):2387–93.

    Article  PubMed  Google Scholar 

  22. Reddy D, Siegel CA, Sands BE, et al. Possible association between isotretinoin and inflammatory bowel disease. Am J Gastroenterol. 2006;101:1569–73.

    Article  PubMed  CAS  Google Scholar 

  23. 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;105:1986–93.

    Article  PubMed  Google Scholar 

  24. 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):2610–6.

    Article  PubMed  CAS  Google Scholar 

  25. Alhusayen RO, Juurlink DN, Mamdani MM, et al. Isotretinoin use and the risk of inflammatory bowel disease: a population-based study. J Invest Dermatol. Epub 2012 Oct 25.

  26. Popescu CM, Popescu R. Isotretinoin therapy and inflammatory bowel disease. Arch Dermatol. 2011;147(6):724–9.

    Article  PubMed  Google Scholar 

  27. Maloney ME, Stone SP. Isotretinoin and iPledge: a view of results. J Am Acad Dermatol. 2011;65:418–9.

    Article  PubMed  Google Scholar 

  28. US Food and Drug Administration. 2007 Drug Safety and Risk Management Advisory Committee, Dermatologic and Ophthalmologic Drugs Advisory Committee. Briefing document: IPLEDGE year one update. Available from URL: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4311b1-02-ipledge.pdf [Accessed 2012 May].

  29. Shin J, Cheetham TC, Wong L, et al. The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system. J Am Acad Dermatol. 2011;65:1117–25.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No sources of funding were received to prepare this article. The authors have no conflicts of interest that are directly relevant to the content of this article.

Author information

Authors and Affiliations

  1. Department of Dermatology, Indiana University, 545 Barnhill Dr, Emerson Hall 139, Indianapolis, IN, 46202, USA

    Stephen E. Wolverton

  2. Department of Dermatology, University of Alabama, Birmingham, AL, USA

    Julie C. Harper

Authors
  1. Stephen E. Wolverton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julie C. Harper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen E. Wolverton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wolverton, S.E., Harper, J.C. Important Controversies Associated with Isotretinoin Therapy for Acne. Am J Clin Dermatol 14, 71–76 (2013). https://doi.org/10.1007/s40257-013-0014-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-013-0014-z

Keywords

Search

Navigation