Introduction to Accutane

Accutane (isotretinoin), or Roaccutane as it is known in parts of the world, was discovered in 1979 when it was first given to patients with severe acne, most of whom reacted with dramatic and permanent clearing of their acne symptoms. It is a vitamin A derivative (13-cis-retinoic acid) that is administered orally in pill form with a meal that contains an adequate amount of fat,1 normally for 15-20 weeks (3.5-4.5 months),2 although it is also sometimes prescribed at lower dosages for up to six months or longer. It was originally recommended for people with severe acne that did not respond to other treatments,3 but has gained in popularity in the past 25 years and is prescribed more and more frequently for less severe acne.4-6 This practice is controversial because Accutane is a systemic medication that affects every bodily system and can cause lifelong side effects to the user. Accutane need not be paired with other medications.7

How Accutane (isotretinoin) Works

Exactly how Accutane works on a cellular level is unknown but we do know that it affects four ways that acne develops.

  1. It dramatically reduces the size of the skin's oil glands (35%-58%) and even more dramatically reduces the amount of oil these glands produce (around 80%).8-11
  2. Acne bacteria (P. acnes) live in skin oil. Since oil is dramatically reduced, so is the amount of acne bacteria in the skin.9
  3. It slows down how fast the skin produces skin cells inside the pore, which helps pores from becoming clogged in the first place.11-12
  4. It has anti-inflammatory properties.11-12

Although acne may get worse within the first month of Accutane use for about 30% of patients, the ultimate results are usually dramatic.13 Accutane works to achieve partial or complete clearance of acne in about 95% of people who complete a cycle, regardless of whether they have inflammatory or non-inflammatory acne.14 The majority of people who take it experience long-term remission of acne symptoms. Studies show relapse rates between 14.6% to 52%, with a real-world average of about 1/3 of people experiencing a relapse. In these cases sometimes a second course is given.11,7,9,14-19

This relapse rate is dose-dependent. Patients who receive a cumulative dose of 100-120mg/kg see the best results and lowest relapse rates. Patients who receive a lower dose relapse more frequently. Daily dosage depends on how much the patient weighs; 0.5mg-2mg / kg is typical.1,15,17

Other factors that increase the chance of relapse are:

  • male gender
  • severe acne
  • not taking isotretinoin with an adequate amount of dietary fat
  • hormonal imbalances like poly-cystic ovary syndrome (PCOS) in women

Low dosing: Traditionally, most doctors prescribe high doses of at least 1mg/kg / day for relatively short periods of time (15-20 weeks). However, because many people develop severe side effects from Accutane, more recently clinicians started testing lower doses of Accutane administered over a longer period of time. Initial data is showing that patients with mild to moderate acne may be able to achieve long-term remission with significantly lower dosages, and thus suffer fewer side effects,20-22 including lower incidence of scarring. For people with more severe acne, staying on a lower dose of Accutane for a longer period of time until the full 120mg/kg cumulative dose is achieved may be a way to produce long-term remission with significantly fewer side effects.23 The current recommendation based on this initial research is that the cumulative dose—the amount of Accutane that accumulates in the body—is the most important factor that determines the success of the treatment.1 A good explanation on how to reach a desired cumulative dose of Accutane was published in the Journal of Clinical and Aesthetic Dermatology:

 If a patient weighs 70kg, the cumulative total dose target of 120mg/kg for his or her course of therapy would be 8400mg (70kg x 120mg). Considering convenience and the practical consideration of capsule strengths, if the patient was started on 40mg daily (slightly more than 0.5mg/kg / day) for the first month, then increased to 60mg daily (slightly less than 1mg/kg / day) thereafter, it would take five months for the patient to reach the cumulative total dose of 8400mg based on the 120mg/kg target (1200mg [40mg x 30 days/month x 1 month] + 7200mg [60mg x 30 days/month x 4 months]). If the daily dose needs to be lowered due to side effects, the cumulative total dose target can be reached by lengthening the duration of therapy to what is needed to reach 120 to 150mg/kg."3

Intermittent dosing: Intermittent dosing (taking Accutane only one week of every month) also produces fewer side effects but may not work as well. It has been studied twice. In both studies people receiving an intermittent dose ended up receiving a lower cumulative dose, so we do not know if the poorer results are due to the intermittent administration of the drug or the lower cumulative dose. The first study compared an intermittent dose to a regular dose. Researchers gave patients in the intermittent dose group the same dose as patients in the regular dose group but for only one week out of the month. This resulted in only ¼ the cumulative dose after treatment ended. This produced slightly less clearing of acne and more than three times the relapse rate compared to the regular dose group.24 The second study compared a similar intermittent dose for only one week out of the month to a continuous low-dose every day. While exact numbers were not reported, from what we can glean from the study, this resulted in approximately ½ the cumulative dose for the intermittent group when compared to the continuous low dose group. Both groups in this second study achieved completely clear skin by the end of treatment, but more people relapsed in the intermittent group.21

  1. Del Rosso, J. Q. Face to face with oral isotretinoin: a closer look at the spectrum of therapeutic outcomes and why some patients need repeated courses. J Clin Aesthet Dermatol 5, 17–24 (2012).
  2. Ganceviciene, R. & Zouboulis, C. C. Isotretinoin: state of the art treatment for acne vulgaris. J Dtsch Dermatol Ges 8 Suppl 1, S47–59 (2010).
  3. Dreno, B. et al. An expert view on the treatment of acne with systemic antibiotics and/or oral isotretinoin in the light of the new European recommendations. Eur J Dermatol 16, 565–571 (2006).
  4. Chen, K., White, T. J., Juzba, M. & Chang, E. Oral isotretinoin: an analysis of its utilization in a managed care organization. J Manag Care Pharm 8, 272–277 (2002).
  5. Wysowski, D. K., Swann, J. & Vega, A. Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000. J Am Acad Dermatol 46, 505–509 (2002).
  6. Rigopoulos, D., Larios, G. & Katsambas, A. D. The role of isotretinoin in acne therapy: why not as first-line therapy? facts and controversies. Clin Dermatol 28, 24–30 (2010).
  7. Dhir, R., Gehi, N. P., Agarwal, R. & More, Y. E. Oral isotretinoin is as effective as a combination of oral isotretinoin and topical anti-acne agents in nodulocystic acne. Indian J Dermatol Venereol Leprol 74, 187 (2008).
  8. Nelson, A. M., Gilliland, K. L., Cong, Z. & Thiboutot, D. M. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol 126, 2178–2189 (2006).
  9. Plewig, G., Dressel, H., Pfleger, M., Michelsen, S. & Kligman, A. M. Low dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne. J Dtsch Dermatol Ges 2, 31–45 (2004).
  10. Layton, A. The use of isotretinoin in acne. Dermatoendocrinol 1, 162–169 (2009).
  11. Tan, J., Boyal, S., Desai, K. & Knezevic, S. Oral Isotretinoin: New Developments Relevant to Clinical Practice. Dermatol Clin 34, 175–184 (2016).
  12. Ellis, C. N. & Krach, K. J. Uses and complications of isotretinoin therapy. J Am Acad Dermatol 45, S150–157 (2001).
  13. Demircay, Z., Kus, S. & Sur, H. Predictive factors for acne flare during isotretinoin treatment. Eur J Dermatol 18, 452–456 (2008).
  14. Mandekou-Lefaki, I., Delli, F., Teknetzis, A., Euthimiadou, R. & Karakatsanis, G. Low-dose schema of isotretinoin in acne vulgaris. Int J Clin Pharmacol Res 23, 41–46 (2003).
  15. Ng, P. P. & Goh, C. L. Treatment outcome of acne vulgaris with oral isotretinoin in 89 patients. Int J Dermatol 38, 213–216 (1999).
  16. Quereux, G., Volteau, C., N'Guyen, J. M. & Dreno, B. Prospective study of risk factors of relapse after treatment of acne with oral isotretinoin. Dermatology 212, 168–176 (2006).
  17. Haryati, I. & Jacinto, S. S. Profile of acne patients in the Philippines requiring a second course of oral isotretinoin. Int J Dermatol 44, 999–1001 (2005).
  18. Akman, A. et al. Treatment of acne with intermittent and conventional isotretinoin: a randomized, controlled multicenter study. Arch Dermatol Res 299, 467–473 (2007).
  19. Morales-Cardona, C. A. & Sanchez-Vanegas, G. Acne relapse rate and predictors of relapse following treatment with oral isotretinoin. Actas Dermosifiliogr 104, 61–66 (2013).
  20. Rademaker, M., Wishart, J. M. & Birchall, N. M. Isotretinoin 5mg daily for low-grade adult acne vulgaris--a placebo-controlled, randomized double-blind study. J Eur Acad Dermatol Venereol 28, 747–754 (2014).
  21. Boyraz, N. & Mustak, P. K. Comparison of the efficacies of intermittent and continuous low-dose isotretinoin regimens in the treatment of moderate acne vulgaris. Int J Dermatol 52, 1265–1267 (2013).
  22. Borghi, A. et al. Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in achieving stable remission. J Eur Acad Dermatol Venereol 25, 1094–1098 (2011).
  23. Rasi, A., Behrangi, E., Rohaninasab, M. & Nahad, Z. M. Efficacy of fixed daily 20mg of isotretinoin in moderate to severe scar prone acne. Adv Biomed Res 3, 103 (2014).
  24. Lee, J. W. et al. Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. Br J Dermatol 164, 1369–1375 (2011).

Accutane is a systemic medication that affects the entire body. Side effects are numerous and widespread, and affect almost all patients.1 Side effects can be moderate and reversible, but in some cases can be severe or long term.

Accutane side effects
Local Adverse Events: Occurs in:
Cheilitis (inflammation of the lips)
up to 100%
Dry skin
up to 100%
Skin peeling
up to 92.9%
Dry nose
up to 70%
Facial rash
up to 68%
Nose bleed
up to 66.7%
Pruritus (itchy skin)
up to 57.1%
Irritated/dry eyes
up to 52%
Conjunctivitis (pink eye)
up to 50%
Thirst
up to 35.7%
Fingertip peeling
up to 33%
Rash
up to 30%
Loss of hair
up to 29%
Sore mouth
up to 28.6%
Eczema
up to 12.1%
Fissuring of the skin
up to 6.7%
Crusting lesions
up to 6.7%
General Adverse Events: Occurs in:
Fatigue
up to 27%
Headache
up to 24.1%
Joint pain
up to 24%
Insomnia
up to 22%
Muscle ache or cramps
up to 17%
Nausea
up to 18%
Loss of appetite
up to 17%
Eye pain
up to 16%
Abdominal pain
up to 14%
Sunburn
up to 12%
Malaise
up to 10%
Double vision
up to <7.1%
Mood change
up to 7.1%
Dry hair
up to 6.7%
Ptergium (growth on the eye)
up to 6.7%
Photophobia (sensitivity to bright light)
up to 6.7%
Decreased sweating
up to 6.7%
Hordeolum (red painful bump near eyelid)
up to 1.4%
Chalazion (lump near tear gland of eye)
up to 1.4%
Blepharitis (inflammation of eyelid)
up to 1%
Laboratory Adverse Events: Occurs in:
Increase in cholesterol
up to 57%
Increase in triglycerides
up to 43%
Increase in liver enzymes
up to 24.5%
Other Adverse Events:
Teratogenicity:
Isotretinoin is associated with teratogenicity resulting in severe birth defects and spontaneous abortions.
Depression/Suicide:
To date, no causal association has been found between isotretinoin and depression/suicide.
Inflammatory bowel disease:
To date, no causal association has been found between isotretinoin and inflammatory bowel disease.
Celiac disease:
To date, no causal association has been found between isotretinoin and celiac disease.
Bone density:
To date, no causal association has been found between isotretinoin and problems in bone density in young patients using short term isotretinoin.

  1. UpToDate, I. (UpToDate, Inc.).
  2. Health, N. I. o. Isotretinoin, oral, https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=ISOTRETINOIN.
  3. Farrell, L. N., Strauss, J. S. & Stranieri, A. M. The treatment of severe cystic acne with 13-cis-retinoic acid. Evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol 3, 602–611 (1980).
  4. Jones, D. H., King, K., Miller, A. J. & Cunliffe, W. J. A dose-response study of I3-cis-retinoic acid in acne vulgaris. Br J Dermatol 108, 333–343 (1983).
  5. Strauss, J. S. et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 10, 490–496 (1984).
  6. Shahidullah, M., Tham, S. N. & Goh, C. L. Isotretinoin therapy in acne vulgaris: a 10-year retrospective study in Singapore. Int J Dermatol 33, 60–63 (1994).
  7. Kaymak, Y. & Ilter, N. The results and side effects of systemic isotretinoin treatment in 100 patients with acne vulgaris. Dermatol Nurs 18, 576–580 (2006).
  8. Agarwal, U. S., Besarwal, R. K. & Bhola, K. Oral isotretinoin in different dose regimens for acne vulgaris: a randomized comparative trial. Indian J Dermatol Venereol Leprol 77, 688–694 (2011).
  9. Lee, J. W. et al. Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. Br J Dermatol 164, 1369–1375 (2011).
  10. Rademaker, M., Wishart, J. M. & Birchall, N. M. Isotretinoin 5mg daily for low-grade adult acne vulgaris--a placebo-controlled, randomized double-blind study. J Eur Acad Dermatol Venereol 28, 747–754 (2014).
  11. Ahmad, H. M. 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 28, 151–157 (2015).
  12. Lester, R. S., Schachter, G. D. & Light, M. J. Isotretinoin and tetracycline in the management of severe nodulocystic acne. Int J Dermatol 24, 252–257 (1985).
  13. Oprica, C., Emtestam, L., Hagstromer, L. & Nord, C. E. Clinical and microbiological comparisons of isotretinoin vs. tetracycline in acne vulgaris. Acta Derm Venereol 87, 246–254 (2007).
  14. Tan, J. et al. A treatment for severe nodular acne: a randomized investigator-blinded, controlled, noninferiority trial comparing fixed-dose adapalene/benzoyl peroxide plus doxycycline vs. oral isotretinoin. Br J Dermatol 171, 1508–1516 (2014).
  15. Jacobs, D. G., Deutsch, N. L. & Brewer, M. Suicide, depression, and isotretinoin: is there a causal link? J Am Acad Dermatol 45, S168–175 (2001).
  16. Hull, P. R. & D'Arcy, C. Isotretinoin use and subsequent depression and suicide: presenting the evidence. Am J Clin Dermatol 4, 493–505 (2003).
  17. Strahan, J. E. & Raimer, S. Isotretinoin and the controversy of psychiatric adverse effects. Int J Dermatol 45, 789–799 (2006).
  18. Magin, P., Pond, D. & Smith, W. Isotretinoin, depression and suicide: a review of the evidence. Br J Gen Pract 55, 134–138 (2005).
  19. 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 48, 41–46 (2009).
  20. Suarez, B., Serrano, A., Cova, Y. & Baptista, T. Isotretinoin was not associated with depression or anxiety: A twelve-week study. World J Psychiatry 6, 136–142 (2016).
  21. Rosa, F. W. Teratogenicity of isotretinoin. Lancet 2, 513 (1983).
  22. Zomerdijk, I. M. et al. Isotretinoin exposure during pregnancy: a population-based study in The Netherlands. BMJ Open 4, e005602 (2014).
  23. Lee, Y. H. et al. Laboratory Monitoring During Isotretinoin Therapy for Acne: A Systematic Review and Meta-analysis. JAMA Dermatol 152, 35–44 (2016).
  24. Etminan, M., Bird, S. T., Delaney, J. A., Bressler, B. & Brophy, J. M. Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data. JAMA Dermatol 149, 216–220 (2013).
  25. Racine, A. et al. Isotretinoin and risk of inflammatory bowel disease: a French nationwide study. Am J Gastroenterol 109, 563–569 (2014).
  26. Lee, S. Y., Jamal, M. M., Nguyen, E. T., Bechtold, M. L. & Nguyen, D. L. Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. Eur J Gastroenterol Hepatol 28, 210–216 (2016).
  27. Lebwohl, B. et al. Isotretinoin use and celiac disease: a population-based cross-sectional study. Am J Clin Dermatol 15, 537–542 (2014).
  28. Rashtak, S. et al. Isotretinoin Exposure and Risk of Celiac Disease. PLoS One 10, e0135881 (2015).
  29. DiGiovanna, J. J. et al. Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne. J Am Acad Dermatol 51, 709–717 (2004).
  30. Tekin, N. S., Ozdolap, S., Sarikaya, S. & Keskin, S. I. Bone mineral density and bone turnover markers in patients receiving a single course of isotretinoin for nodulocystic acne. Int J Dermatol 47, 622–625 (2008).
  31. Neudorfer, M. et al. Ocular adverse effects of systemic treatment with isotretinoin. Arch Dermatol 148, 803–808 (2012).
  32. Rademaker, M. Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin. Australas J Dermatol 51, 248–253 (2010).
Accutane pregancy

Accutane is the number one teratogen on the market. A teratogen is a medication that interferes with normal development of the fetus and causes birth defects. Shortly after Accutane became available on the market, the Centers for Disease Control (CDC) reported that a large proportion of pregnancies in women who are exposed to Accutane result in spontaneous abortions and birth defects and advised against the use of Accutane by pregnant women.1 Birth defects include:

  • skull
  • ear
  • eye
  • facial
  • central nervous system
  • cardiovascular
  • thymus and parathyroid abnormalities
  • death2

Clinical research shows extremely high risk for birth defects if Accutane is taken by pregnant women.3 The effects and risks of Accutane on unborn children are so severe that the FDA approved the iPledge program, which requires female patients of childbearing age to commit to using two (2) forms of birth control while on Accutane.4

However, despite warnings to women not to get pregnant while using Accutane, studies published in Canada, the Netherlands, and the UK report a range of 11-24 per 1000 women getting pregnant while on Accutane.5-7 This is lower than the pregnancy rate in the general population of these countries which stands at approximately 50 per 1000 women, but is still unacceptably high, leading to tragic outcomes.

Another study performed in California looked at rates of pregnancy before and after the iPledge program was implemented. Thankfully, they found lower rates of pregnancy among women using Accutane in California, but found that the iPledge program had only modest results. Before iPledge. 3.1 women in California per 1000 taking Accutane got pregnant, and after iPledge this number dropped to 2.7. Researchers stated, “We found that most women on isotretinoin depend on contraceptive methods that require considerable adherence to be effective. Unfortunately, our results suggest that this degree of adherence is unrealistic for many women.”8 Abstinence, condoms, and the birth control pill were all cited as areas of non-adherence.

The iPledge program

Roche started with a program called SMART (System to Manage Accutane Related Teratogenicity) in 2000, which became the iPLEDGE program in March, 2006. Female patients of childbearing age are required to use two (2) forms of birth control while on Accutane.4,10

iPLEDGE program telephone: 1-866-495-0654
iPLEDGE program website: ipledgeprogram.com

  1. CDC. Epidemiologic Notes and Reports Isotretinoin -- A Newly Recognized Human Teratogen. Morbidity and Mortality Weekly Report 33, 171–173 (1986).
  2. Hull, P. R. & D'Arcy, C. Acne, depression, and suicide. Dermatol Clin 23, 665–674 (2005).
  3. Magin, P., Pond, D. & Smith, W. Isotretinoin, depression and suicide: a review of the evidence. Br J Gen Pract 55, 134–138 (2005).
  4. 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 48, 41–46 (2009).
  5. Henry, D. et al. Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy. CMAJ 188, 723–730 (2016).
  6. Zomerdijk, I. M. et al. Isotretinoin exposure during pregnancy: a population-based study in The Netherlands. BMJ Open 4, e005602 (2014).
  7. Berard, A. et al. Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol 63, 196–205 (2007).
  8. Collins, M. K. et al. Compliance with pregnancy prevention measures during isotretinoin therapy. J Am Acad Dermatol 70, 55–59 (2014).
  9. Shin, J. et al. The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system. J Am Acad Dermatol 65, 1117–1125 (2011).
  10. Sundstrom, A. et al. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ 341, c5812 (2010).
Suicide and depression

Patients have reported depressive symptoms while taking Accutane since the drug hit the market in 1982. Whether the drug causes these depressive feelings remains a subject of intense debate. There are, after all, millions of people taking the drug, and there are bound to be people experiencing depression amongst them. Despite the confusion around this topic, Roche Pharmaceuticals, the makers of Accutane, added a warning to its label regarding suicide and depression in 1998.

Media coverage on the topic spiked in 2000 when Michigan Congressman Bart Stupak's son BJ committed suicide while on Accutane. Research began in earnest to determine whether there is a causal link between Accutane, suicide, and depression.1-2

Quite a few studies have been conducted since. These have included large population-based cohort studies, retrospective analysis studies, relative risk estimates, prospective, observational, and longitudinal studies, and questionnaires performed in the United States and around the world.3-16 The first of these studies showed no conclusive evidence linking Accutane with depression or suicide.1-2 As the studies mounted, the data continued to show no evidence of a link.7-9,17 One study published in The New England Journal of Medicine found "431 cases of depression, suicidal ideation, suicide attempts, or suicide in U.S. patients treated with isotretinoin," within a 10 year period. The article went on to note that the numbers listed do not exceed the U.S. suicide rate.18

If a researcher were to examine the evidence from 2000 until 2005, he or she would likely conclude that there is no evidence linking Accutane with suicide or depression.7-9 However, as is often the case, further analysis showed limitations to many of the studies.19-20 A general overview published in 2006 by the International Journal of Dermatology noted, "the overall lack of concrete scientific data limits any conclusion that can be drawn about a causal relationship between isotretinoin and psychiatric adverse events."21

Then, in 2006, mice injected with the drug exhibited depression-related behaviour. While animal studies often do not reflect human models, it was marginally intriguing.10 But even more provocative was a large cohort case-crossover study published in 2008 by the Journal of Clinical Psychiatry, which was the first controlled study to find a correlation between Accutane, suicide, and depression, albeit relatively minor.11 More recent studies have leant more credibility to the argument that Accutane does not negatively affect depression or mood,5,6 and several studies show significant improvements to depression, anxiety, and obsessive thoughts,12-16 presumably due to the power of Accutane to clear acne and thus increase quality of life.

A review of literature on the link between Accutane in depression in 2015 stated, “The major part of the dermatology community states that there is no causal link between isotretinoin and depression with this postulate: acne causes anxiety and depression; treating acne with isotretinoin is a way to manage depression.” However, there is still controversy, with critics pointing out the dermatology community’s tendency to not understand depression as well as the psychiatric community. “Literature studies have demonstrated two opposing views as to the role of isotretinoin from two differing clinical specialties. The psychiatric literature…suggests a causal link between isotretinoin and depression. The dermatological literature suggests that acne is an independent risk factor for depression and isotretinoin could be used to improve depression by treating acne and improving self-image. These differing views could be explained by a recruitment bias. Dermatologists may not have been aware of the occurrence of psychiatric disorders.”22

The preponderance of the evidence at this point is that Accutane does not appear to be linked with suicide and depression.20,23 However, to be safe, it is important for anyone taking Accutane to closely monitor their mental health while on the drug.4,1,24 Doctors prescribing Accutane can also check for signs of depression. A paper published in the Journal of the American Academy of Dermatology in 2016 recommends that all patients who are prescribed Accutane be screened for depression. The authors of the paper state, “Regardless of whether depression in these patients is rooted in the underlying acne or its treatment, the prevalence and serious nature of depression, suicide, and suicidal ideation demand attention. Given the chronic nature of acne treatment, dermatologists are uniquely situated to help screen for depression and suicidal ideation. It is our duty to care for all aspects of our patients' health, including their mental health.”25 The paper also provided a screening tool for depression, which allows physicians to quickly screen patients who are at high risk of developing depression while taking Accutane. The tool consists of a series of questions and if a patient receives a score of 3 or more, he or she should be further examined to determine if they could safely take Accutane.

Over the past 2 wk, how often have you been bothered by any of the following problems? Not at all Several days More than half the days Nearly every day
1. Little interest or pleasure in doing things 0 1 2 3
2. Feeling down, depressed, or hopeless 0 1 2 3
3. Trouble falling or staying asleep, or sleeping too much 0 1 2 3
4. Feeling tired or having little energy 0 1 2 3
5. Poor appetite or overeating 0 1 2 3
6. Feeling bad about yourself–or that you are a failure or have let yourself or your family down 0 1 2 3
7. Trouble concentrating on things, such as reading the newspaper or watching television 0 1 2 3
8. Moving or speaking so slowly that other people could have noticed? Or the opposite–being so fidgety or restless that you have been moving around a lot more than usual. 0 1 2 3
9. Thoughts that you would be better off dead or of hurting yourself in some way 0 1 2 3
  1. Jacobs, D. G., Deutsch, N. L. & Brewer, M. Suicide, depression, and isotretinoin: is there a causal link? J Am Acad Dermatol 45, S168–175 (2001).
  2. Jick, S. S., Kremers, H. M. & Vasilakis-Scaramozza, C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol 136, 1231–1236 (2000).
  3. Hull, P. R. & D'Arcy, C. Acne, depression, and suicide. Dermatol Clin 23, 665–674 (2005).
  4. Magin, P., Pond, D. & Smith, W. Isotretinoin, depression and suicide: a review of the evidence. Br J Gen Pract 55, 134–138 (2005).
  5. 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 48, 41–46 (2009).
  6. Sundstrom, A. et al. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ 341, c5812 (2010).
  7. Chia, C. Y., Lane, W., Chibnall, J., Allen, A. & Siegfried, E. Isotretinoin therapy and mood changes in adolescents with moderate to severe acne: a cohort study. Arch Dermatol 141 557–560 (2005).
  8. Hersom, K., Neary, M. P., Levaux, H. P., Klaskala, W. & Strauss, J. S. Isotretinoin and antidepressant pharmacotherapy: a prescription sequence symmetry analysis. J Am Acad Dermatol 49 424–432 (2003).
  9. Ferahbas, A. et al. A pilot study evaluating anxiety and depressive scores in acne patients treated with isotretinoin. J Dermatolog Treat 15, 153–157 (2004).
  10. O'Reilly, K. C., Shumake, J., Gonzalez-Lima, F., Lane, M. A. & Bailey, S. J. Chronic administration of 13-cis-retinoic acid increases depression-related behavior in mice. Neuropsychopharmacology 31, 1919–1927 (2006).
  11. Azoulay, L., Blais, L., Koren, G., LeLorier, J. & Berard, A. Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study. J Clin Psychiatry 69, 526–532 (2008).
  12. Yesilova, Y., Bez, Y., Ari, M., Kaya, M. C. & Alpak, G. Effects of isotretinoin on obsessive compulsive symptoms, depression, and anxiety in patients with acne vulgaris. J Dermatolog Treat 23 268–271 (2012).
  13. Ergun, T. et al. Isotretinoin has no negative effect on attention, executive function and mood. J Eur Acad Dermatol Venereol 26 431–439 (2012).
  14. Marron, S. E., Tomas-Aragones, L. & Boira, S. Anxiety, depression, quality of life and patient satisfaction in acne patients treated with oral isotretinoin. Acta Derm Venereol 93, 701–706 (2013).
  15. Nevoralova, Z. & Dvorakova, D. Mood changes, depression and suicide risk during isotretinoin treatment: a prospective study. Int J Dermatol 52 (2013).
  16. Yesilova, Y., Bez, Y., Ari, M. & Turan, E. Effects of isotretinoin on social anxiety and quality of life in patients with acne vulgaris: a prospective trial. Acta Dermatovenerol Croat 20 80–83 (2012).
  17. 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 14, e227–233 (2007).
  18. Wysowski, D. K., Pitts, M. & Beitz, J. Depression and suicide in patients treated with isotretinoin. N Engl J Med 344, 460 (2001).
  19. Marqueling, A. L. & Zane, L. T. Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Semin Cutan Med Surg 24, 92–102 (2005).
  20. Wysowski, D. K., Pitts, M. & Beitz, J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 45, 515–519 (2001).
  21. Strahan, J. E. & Raimer, S. Isotretinoin and the controversy of psychiatric adverse effects. Int J Dermatol 45, 789–799 (2006).
  22. Ludot, M., Mouchabac, S. & Ferreri, F. Inter-relationships between isotretinoin treatment and psychiatric disorders: Depression, bipolar disorder, anxiety, psychosis and suicide risks. World J Psychiatry 5, 222–227 (2015).
  23. Wolverton, S. E. & Harper, J. C. Important controversies associated with isotretinoin therapy for acne. Am J Clin Dermatol 14, 71–76 (2013).
  24. Thiboutot, D. & Zaenglein, A. Isotretinoin and affective disorders: thirty years later. J Am Acad Dermatol 68, 675–676 (2013).
  25. Schrom, K., Nagy, T. & Mostow, E. Depression screening using health questionnaires in patients receiving oral isotretinoin for acne vulgaris. J Am Acad Dermatol 75, 237–239 (2016).
High fat foods

Isotretinoin is a fat-soluble molecule, meaning that it is best absorbed into the blood if taken with a meal that contains an adequate amount of fat.1-2 According to drug labeling information submitted to the U.S. National Library of Medicine by the makers of Accutane, "Both peak plasma concentration (Cmax) and the total exposure (AUC) of isotretinoin were more than doubled following a standardized high-fat meal when compared with Accutane given under fasted conditions. Therefore, Accutane capsules should always be taken with food. Failure to take Accutane with food will significantly decrease absorption."3 This failure to take Accutane with fat-containing meals may account for some of the relapse that we see post-Accutane.

So what kind of meal should be eaten when taking Accutane, and how much dietary fat should it contain? So far only 2 studies have been performed. The first asked participants to ingest approximately 20g of fat (2 poached eggs, toast with margarine, plus 8oz. of skimmed milk), and found that this was enough to approximately double the absorption of Accutane.2 The second asked participants to ingest 50g of fat (1 bagel, 2 tablespoons of peanut butter, 5 slices of bacon, 6oz. of apple juice, and 1 donut), and found that this was also enough to approximately double the absorption rate.4 Further research is required to determine exactly how much fat one must optimally ingest to reach maximum isotretinoin levels in the blood, but suffice it to say that isotretinoin must be taken with a meal which contains dietary fat to deliver its full potential. Based on the research thus far, it is prudent to ingest at least 20 grams of fat when taking a daily dose of isotretinoin.5

One exception – Absorica™: In 2012, the FDA approved a new version of isotretinoin, called isotretinoin-Lidose, for sale in the United States that is marketed under the brand name Absorica. This formulation encapsulates isotretinoin in fat molecules and therefore reduces the need to take it with a fatty meal.1,4 The package insert states that Absorica "(1) is bioequivalent with Accutane when both are taken with a high fat meal; (2) has 83% greater absorption than Accutane under fasted conditions; (3) is not interchangeable with generic products of Accutane, and (4) can be dosed without regard to meals."7 While data does show that absorption of Absorica is significantly greater than absorption of regular isotretinoin on an empty stomach, the claim that Absorica can be dosed without regard to meals may be skewed, since data show that even with Absorica, the amount of isotretinoin in the blood remains significantly higher when taken with a high-fat-containing meal.4

Thus, it may also be prudent to take Absorica with a meal which contains an adequate amount of dietary fat. In addition, since there are no generic forms of Absorica. It is considerably more expensive than other forms of isotretinoin.8

Drug Cost for 30 Days Treatment at 60mg/day
Absorica
$ 1416.82
Amnesteem *
$ 551.26
Claravis *
$ 710.70
Myorisan *
$ 550.50
Sotret *
$ 612.51

* Generic forms of isotretinoin


  1. Tan, J. & Knezevic, S. Improving bioavailability with a novel isotretinoin formulation (isotretinoin-Lidose). Skin Therapy Lett 18, 1–3 (2013).
  2. Colburn Wa Fau - Gibson, D. M., Gibson Dm Fau - Wiens, R. E., Wiens Re Fau - Hanigan, J. J. & Hanigan, J. J. Food increases the bioavailability of isotretinoin. J Clin Pharmacol 23, 534–539 (1983).
  3. Roche Laboratories Inc. Accutane (isotretinoin) capsule, liquid filled. https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=8655#section-13 (2006).
  4. Webster, G. F., Leyden, J. J. & Gross, J. A. 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 69, 762–767 (2013).
  5. Tan, J., Boyal, S., Desai, K. & Knezevic, S. Oral Isotretinoin: New Developments Relevant to Clinical Practice. Dermatol Clin 34, 175–184 (2016).
  6. US Department of Health and Human Services, F. a. D. A., Centre for Drug Evaluation and Research (CDER). Guidance for industry: food-effect bioavailability and fed bioequivalence studies. (2002).
  7. Ranbaxy Laboratories Inc. ABSORBICA [Prescribing Information]. (2012).
  8. In Brief: Absorica for acne. JAMA 311, 2123 (2014).

Gerald Peck and co-workers from the NIH (National Institutes of Health) in Bethesda, Maryland first studied isotretinoin in patients with skin cell disorders. They accidentally found that it also worked on patients with severe acne. Isotretinoin was registered in 1979, released in the United States in 1982 as Accutane, and released in Europe in 1985 as Roaccutane.

Roche's patent expired in 2002, and manufacturers began selling generic forms of the drug.

In June, 2009, shortly after a jury awarded $33 million in damages to people who claimed Accutane caused bowel disease, Roche decided to discontinue selling brand name, Accutane. The company cited declining sales as their reason.

Topical isotretinoin exists but does not produce the results of oral isotretinoin. It is largely of historical significance in acne treatment.

According to the FDA:

  1. "Buying (Accutane) over the Internet bypasses important procedures to ensure that patients can take this drug safely. When these procedures are ignored, isotretinoin can cause serious and harmful side effects."
  2. You should NEVER buy Accutane (isotretinoin) without first seeing your healthcare professional.
  3. You should NEVER take Accutane (isotretinoin) or any of the generic versions of Accutane if you are pregnant or trying to get pregnant or could accidentally become pregnant.
  4. Some websites sell prescription drugs without a prescription. This is illegal and DANGEROUS.

 Buying Accutane or any other prescription over the Internet often means you will receive pills that contain little or no active ingredient, or in some cases, a different medication entirely. Buying Accutane over the Internet is not only illegal, it is potentially dangerous and is also a waste of money.4 I agree strongly with the FDA. NEVER buy Accutane over the Internet."

As a critical sociology major in college, I learned that it is important for an author to present his or her bias. Because we are human and it is impossible to be completely unbiased, the presentation of bias allows the reader to take the author's bias into account when absorbing content.

My bias: I suffered with moderately severe acne in my adolescence and early adulthood. I took Accutane at age 20 but do not recall the dosage my doctor prescribed. It cleared me up completely within weeks. I transformed from a shy introvert to an outgoing college student. As a result of my skin clearing up, my mental state felt relatively light and good, albeit still somewhat anxious as I had always been. My short-term side effects included severely dry lips, extremely dry skin, dry eyes, and sometimes severe joint pain. I now live with two long-term conditions which may be from taking Accutane or may be coincidence. Since Accutane, whenever I sprint or exert myself in quick bursts my joints react with pain and inflammation, thus limiting my sports endeavors. I also have a mild version of an eye condition called pterygium, which is an irreversible and not-so-attractive growth on the white part of both eyes. My acne relapsed post-Accutane somewhat aggressively to what would be described as moderate acne. I am now able to control my acne symptoms with The Acne.org Regimen."