Introduction to Accutane

Accutane (also known as isotretinoin), or Roaccutane as is also 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 serious medication which can cause long-lasting side effects. It is often referred to as the 'nuclear option' for acne. Accutane need not be paired with other medications.7


Exactly how Accutane works on a cellular level is unknown but we do know that it affects all 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%).8-9
  • 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.10
  • 4. It has anti-inflammatory properties.10

Although acne may get worse within the first month of Accutane use for about 30% of patients, the ultimate results are usually dramatic.11 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.12 The majority of people who take it see their acne effectively cured, experiencing long-term remission of acne symptoms. Studies show an average relapse rate of around 33%, and in these cases sometimes a second course is given.7,9,12-17 This relapse rate is dose-dependent.13 Patients who receive a cumulative dose of 100-120 mg/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; 0.5 mg - 2 mg/kg is typical.15

Low and intermittent dosing: Researchers have published several studies attempting to gauge whether people with mild to moderate acne can achieve long term remission of acne with lower dosages of Accutane. Initial data is showing that people with mild to moderate acne may be able to achieve long term remission with significantly lower dosages, and thus suffer less side effects,18-20 including lower incidence of scarring. Relapse rates with lower dosages do not seem to increase, leading some researchers to posit that it is not cumulative dose that brings about permanent clearing as much as it is the length of time that the oil glands are suppressed.20 Intermittent dosing (taking Accutane only 1 week of every month) appears to work less well, producing significantly poorer outcomes for more than half of the patients studied.19,21

  1. Del Rosso, JQ. “Face to face with oral isotretinoin: a closer look at the spectrum of therapeutic outcomes and why some patients need repeated courses.” The Journal of Clinical and Aesthetic Dermatology. 2012; 5(11): 17-24.
  2. Ganceviciene R and Zouboulis CC. "Isotretinoin: State of the art treatment for acne vulgaris." Journal of the German Society of Dermatology. 2009; 8 Suppl. 1: S47-S59.
  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." European Journal of Dermatology. 2006; 16(5): 565-71.
  4. Chen K, et al. "Oral isotretinoin: an analysis of its utilization in a managed care organization." Journal of Managed Care Pharmacy. 2002; 8(4): 272-7.
  5. Wysowski DK, Swann J and Vega A. "Use of isotretinoin (Accutane) in the United States: Rapid increase from 1992 through 2000." Journal of the American Academy of Dermatology. 2002; 46(4): 505-9.
  6. Rigopoulos D, Larios G and Katsambas AD. "The role of isotretinoin in acne therapy: Why not as first-line therapy? Facts and controversies." Clinics in Dermatology. 2010; 28(1): 24-30.
  7. Dhir R, et al. "Oral isotretinoin is as effective as a combination of oral isotretinoin and topical anti-acne agents in nodulocystic acne." Indian Journal of Dermatology, Venereology and Leprology. 2008; 74(2): 187.
  8. Nelson AM, et al. "13-cis-retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes." Journal of Investigative Dermatology. 2006; 126(10): 2178-89.
  9. Plewig G, et al. "Low dose isotretinoin combined with tretinoin is effective to correct abnormalities in acne." Journal of the German Society of Dermatology. 2004; 2(1): 31-45.
  10. Ellis CN and Krach KJ. "Uses and complications of isotretinoin therapy." Journal of American Academy of Dermatology. 2001; 45(5): S150-7.
  11. Demircay Z, Kus S and Sur H. "Predictive factors for acne flare during isotretinoin treatment." European Journal of Dermatology. 2008; 18(4): 452-456.
  12. Mandekou-Lefaki I, et al. "Low-dose schema of isotretinoin in acne vulgaris." International Journal of Clinical Pharmacological Research. 2003; 23(2-3): 41-6.
  13. Ng PP and Goh CL. "Treatment outcome of acne vulgaris with oral isotretinoin in 89 patients." International Journal of Dermatology. 1999; 38(3): 213-6.
  14. Quereux G, et al. "Prospective study of risk factors of relapse after treatment of acne with oral isotretinoin." Dermatology. 2006; 212(2): 168-76.
  15. Haryati I and Jacinto SS. "Profile of acne patients in the Philippines requiring a second course of isotretinoin." International Journal of Dermatology. 2005; 44(12): 999-1001.
  16. Akman A, et al. "Treatment of acne vulgaris with intermittent and conventional isotretinoin: a randomized, controlled multicenter study." Archives of Dermatological Research. 2007; 299(10): 467-73.
  17. Morales-Cardona CA and Sanchez-Vanegas G. “Acne relapse rate and predictors of relapse following treatment with oral isotretinoin.” Actas Dermo-Sifiliograficas. 2013; 104(1): 61-6.
  18. Rademaker M, Wishart JM and Birchall NM. “Isotretinoin 5 mg daily for low-grade adult acne vulgaris – a placebo-controlled, randomized double blind study.” Journal of the European Academy of Dermatology and Venereology. 2013; [ahead of print].
  19. Boyraz N and Mustak PK. “Comparison of the efficacies of intermittent and continuous low-dose isotretinoin regimens in the treatment of moderate acne vulgaris.” International Journal of Dermatology. 2013; [ahead of print].
  20. Borghi A, et al "Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: Efficacy in achieving stable remission." Journal of the American Academy of Dermatology. 2011; 25(9): 1094-1098.
  21. Lee JW, et al. "Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: A randomized, controlled comparative study." British Journal of Dermatology. 2011; 164(6): 1369-1375.

Elevated liver enzymes

AKA Hepatotoxicity. Clinical research found this to occur in 15% of cases.3,28

Inflamed pancreas

AKA Pancreatitis. Clinical research found this to rarely occur.

Respiratory symptoms

Difficulty breathing (bronchospasms, respiratory infection, and voice alteration).8

Dry lips

Clinical research found this to occur in 92% of cases.3,8

Dry skin

AKA Xerosis. Clinical research found this to occur in 57% of cases.3,7-8

Nosebleed

AKA Epistaxis. Clinical research found excessively dry nose to occur in 30% of cases.8

Rash (including eczema)

Eczema is a medical condition in which patches of skin become rough and inflamed, with blisters that cause itching and bleeding. Clinical research has shown it may be exacerbated by Accutane use.7-8 Other, more rare forms of facial rash have been reported.10

Hair loss

A small percentage of people are affected on a short-term basis and at a low level.7-8

Inflammation of the lips

Cheilitis.8

Hives

AKA Uticaria. Rare cases of allergic reaction to Accutane, including hives, have been reported.7-8

Alopecia

Alopecia is a condition that results in loss of hair from the scalp and sometimes other areas of the body. Rare cases have been reported.7

Hair overgrowth in women

Rare cases of hirsutism have been reported.

Nail abnormalities

Extremeley rare cases of nail abnormalities have been reported.

Yellowish deposits on eyelids

AKA Xanthomas. Clinical research found this to rarely occur.

Dry mouth

Increased sunburn susceptibility

Oozing, bleeding skin bumps

Bleeding & inflammation of the gums

Birth defects

Accutane is the #1 prescribed teratogenic (causes birth defects) medication in the United States.2

Abnormal menses (women)

Muscle pain

AKA Myalgia. Clinical research found this to occur in 15% to 50% of cases.7-8,14,19-20

Low back pain

Clinical research found this to occur in 30% of cases.

Joint pain

AKA Arthralgia. Clinical research found this to occur in 15% to 35% of cases.7-8,13-16

Overgrowth of bone

AKA hyperostosis. Clinical research found detectable changes to occur in 10% of cases.8,11

Tendonitis

Inflammation of a tendon.7-8

Arthritis

Temporary yet painful inflammation and stiffness of the joints.8,15

Acute, long lasting arthritis

Clinical research found this to occur extremely rarely.14,17-18

Bone, tendon, and ligament calcification

Calcification is hardening of the bone, tendon, or ligament caused by the deposition of or conversion into calcium carbonate or some other insoluble calcium compounds; calcified cartilage.11 Clinical research found this to occur only in high-dose, long-term (several years) Accutane therapy.12

Rapid breakdown of muscle tissue

AKA Rhabdomyolysis. Clinical research found this to occur in rare cases.8

Headaches

Clinical research found this occurred in 10% to 28% of cases.9,29

Vision problems

Certain: abnormal oil secretion in the eye (abnormal meibomian gland secretion), inflamed mucus membrane that lines the eye (blepharoconjunctivitis), cornea becomes less transparent (corneal opacities), loss of night vision (decreased dark adaptation), decreased tolerance to contact lenses, decreased vision, increased salt concentration in tears (increased tear osmolarity), inflamed cornea (keratitis), oil gland atrophy in the eye (meibomian gland atrophy), near- or shortsightedness (myopia), eye discomfort (ocular discomfort), dry eye (ocular sicca), excessive sensitivity to light (photophobia), birth defects regarding the eyes (teratogenic ocular abnormalities).7,8

Probable/likely: decreased color vision [reversible], permanent loss of night vision AKA loss of dark adaptation.3,9

Possible: permanent dry eyes AKA keratoconjunctivitis sicca.7-8

As a side note, the FAA {United States Federal Aviation Administration} is considering more stringent rules regarding pilots who have been exposed to Accutane.9

Pressure within the skull

AKA intracranial hypertension. Clinical research found this to occur very rarely.8

Neurological symptoms.

Including dizziness, drowsiness, insomnia, lethargy, malaise, nervousness, tingling/pricking/numbness (paresthesias), seizures, stroke, fainting (syncope), and weakness. Clinical research found this to occur in 16-29% of cases.8

Depression

Depression and suicide have been linked to Accutane in clinical research but as data mounts, it appears unlikely that depression is more commn in people as a result of taking Accutane. More research on the connection between suicide, depression and Accutane is needed. See the Suicide & Depression section for more detailed information on the topic.21-22

Reduced blood flow to the brain

AKA Cerebral ischemia. Clinical research found this to be extremely rare.23

Hearing impairment

"Has been reported" and "may persist after therapy has been discontinued."8

Severe allergy

Rare anaphylactic reactions have been reported in clinical research.8

Low white blood cell count

AKA Neutropenia.26

Inflammatory bowel disease/Crohn's disease/Ulcerative colitis

Although Inflammatory bowel disease (IBD) and Chrohn's disease are often connected with Accutane, clinical research found no correlation. Clinical research did find a weak correlation30-32 between Accutane and ulcerative colitis.27-28

Anal fissure and rectal bleeding

Rare cases have been reported.33

Abnormal blood tests

Elevated triglycerides, cholesterol, transaminase. Clinical research found this to occur in 44%, 31%, and 11% of cases respectively.8,24-25

Blood disease

AKA Agranulocytosis. Clinical research found this to be rare but life-threatening.

Low iron content in blood

AKA Anemia.

Low blood platelet count

AKA Thrombocytopenia.

Lower vitamin levels

Studies have shown reductions in serum folic acid 34 and vitamin E levels.35


  1. Rademaker M. "Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin." Australasian Journal of Dermatology. 2010; 51(4): 248-253.
  2. Honein MA, Paulozzi LJ and Erickson JD. "Continued occurrence of Accutane-exposed pregnancies." Teratology. 2001; 64(3): 142-7.
  3. relsford M and Beute TC. "Preventing and managing the side effects of isotretinoin." Seminars in Cutaneous Medicine and Surgery. 2008; 27(3): 197-206.
  4. erard A, et al. "Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective." British Journal of Clinical Pharmacology. 2007; 63(2): 196-205.
  5. broms L, et al. "What is the best approach to reducing birth defects associated with isotretinoin?" PLoS Medicine. Nov; 3(11): e483.
  6. hin J, et al. "The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system." Journal of the American Academy of Dermatology. 2011 May 10.
  7. oulden V, Layton AM and Cunliffe WJ. "Long-term safety of isotretinoin as a treatment for acne vulgaris." British Journal of Dermatology. 1994; 131(3): 360-3.
  8. cLane J. "Analysis of common side effects of isotretinoin." Journal of the American Academy of Dermatology. 2001; 45(5): S188-94.
  9. urkhart CG. "Another threat to the availability of isotretinoin: ocular side effects have aviation authorities considering restricting use from (even potential) pilots." Dermatology Online Journal. 2008; 14(7): 2.
  10. Barzilai A, et al. "Seborrheic dermatitis-like eruption in patients taking isotretinoin therapy for acne: retrospective study of five patients." American Journal of Clinical Dermatology. 2008; 9(4): 255-61.
  11. DiGiovanna JJ. "Isotretinoin effects on bone." Journal of the American Academy of Dermatology. 2001; 45(5): S176-82.
  12. DiGiovanna JJ, et al. "Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne." Journal of the American Academy of Dermatology. 2004; 51(5): 709-17.
  13. Eksioglu E, et al. "Sacroiliitis and polyneuropathy during isotretinoin treatment." Clinical and Experimental Dermatology. 2008; 33(2): 122-4.
  14. De Francesco V, Stinco G and Campanella M. "Acute arthritis during isotretinoin treatment for acne conglobata." Dermatology. 1997; 194(2): 195.
  15. Bewley AP, et al. "Isotretinoin causing acute aseptic arthropathy." Clinical and Experimental Dermatology. 1995; 20(3): 279.
  16. Kaplan G and Haettich B. "Rheumatological symptoms due to retinoids." Bailliere's Clinical Rheumatology. 1991; 5(1): 77-97.
  17. Hughes RA. "Arthritis precipitated by isotretinoin treatment for acne vulgaris." The Journal of Rheumatology. 1993; 20(7): 1241-2.
  18. Lehucher Ceyrac D. "Acute arthritis after isotretinoin." Dermatology. 1999; 198(4): 406-7.
  19. Kaymak Y, et al. "Creatine phosphokinase values during isotretinoin treatment for acne." International Journal of Dermatology. 2008; 47(4): 398-401.
  20. Dicken CH. "Retinoids: A Review." Journal of American Academy of Dermatology. 1984;11:541-552.21. Kaymak Y, Taner E and Taner Y. "Comparison of depression, anxiety and life quality in acne vulgaris partients who were treated with either isotretinoin or topical agents." International Journal of Dermatology. 2009; 48(1): 41-46.
  21. Sundstrom A, et al. "Association of suicide attempts with acne and treatment with isotretinoin: Retrospective Swedish cohort study." British Medical Journal. 2010 Nov. 11.
  22. Laroche ML, et al. "Cerebral ischemia probably related to isotretinoin." The Annals of Pharmacotherapy. 2007; 41(6): 1073-1076.
  23. Zane LT, et al. "A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris." Archives of Dermatology. 2006; 142(8): 1016-22.
  24. Karadag AS, et al. "Short-term isotretinoin treatment decreases insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels: Does isotretinoin affect growth hormone physiology?" British Journal of Dermatology. 2010; 162(4): 798-802.
  25. Ozdemir MA, et al. "Isotretinoin-induced agranulocytosis." Pediatric Dermatology. 2007; 24(4): 425-6.
  26. Reddy D, et al. "Possible association between isotretinoin and inflammatory bowel disease." American Journal of Gastroenterology. 2006; 101(7): 1569-73.
  27. Crockett SD, et al. "Isotretinoin use and the risk of inflammatory bowel disease: A case-control study." The American Journal of Gastroenterology. 2010; 105(9): 1986-1993.
  28. Erturan I, Naziroglu M and Akkaya VB. “Isotretinoin treatment induces oxidative toxicity in blood of patients with acne vulgaris: a clinical pilot study.” Cell Biochemistry and Function. 2012; 30(7): 552-7.
  29. Neudorfer M, et al. “Ocular adverse effects of systemic treatment with isotretinoin.” JAMA Dermatology. 2012; 148(7): 803-8.
  30. Alhusayen RO, et al. “Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study.” Journal of Investigative Dermatology. 2013; 133(4): 907-12.
  31. Etminan M, et al. “Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data.” JAMA Dermatology. 2013; 149(2): 216-20.
  32. Stobaugh DJ, Deepak P and Ehrenpreis ED. “Alleged isotretinoin-associated bowel disease: Disproportionate reporting by attorneys to the Food and Drug Administration Adverse Event Reporting System.” Journal of the American Academy of Dermatology. 2013; 69(3): 393-8.
  33. Gungor S and Gokdemir G. “Anal fissure and rectal bleeding as a complication of systemic isotretinoin therapy. Dermatologists knows this side effect, what about proctologists?” Colorectal Disease. 2013 [ahead of print].
  34. Javanbakht AM, Pour HM and Tarrahic MJ. “Effects of oral isotretinoin on serum folic acid levels.” Journal of Drugs in Dermatology. 2012; 11(9): 23-24.
  35. Akturk AS, et al. “Effects of isotretinoin on serum vitamin E levels in patients with acne.” International Journal of Dermatology. 2013; 52(3): 363-6.

  Significant reductions in anxiety were observed...after treatment [with isotretinoin], with mitigation of anxiety and depression most robust in those patients with the greatest...improvement [in acne symptoms]. Although a direct cause and effect between use of isotretinoin and depression and suicide has not been established; it may never be. Since we cannot predict which patients may exhibit these symptoms...it is in the best interest of our patients to educate them regarding the signs and symptoms of depression.25

Journal of the American Academy of Dermatology, 2013

Patients have reported depressive symptoms while taking Accutane since shortly after the drug became legal in 1982. Whether the drug caused 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 & 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, 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, depression-related behavior was shown in mice injected with the drug. 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 lent more credibility to the argument that Accutane does not negatively affect depression or mood,5-6 and several 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.

The preponderance of the evidence at this point is that Accutane does not appear to be linked with suicide and depression.22-24 However, to be safe, it is important for anyone taking Accutane to closely monitor their mental health while on the drug.1,4,25 If you find yourself feeling depressed or suicidal, seek help right away.

  1. Jacobs DG, Deutsch NL and Brewer M. "Suicide, depression, and isotretinoin: is there a causal link?" Journal of the American Academy of Dermatology. 2001; 45(5): S168-75.
  2. Jick SS, Kremers HM and Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Archives of Dermatology. 2000; 136(10): 1231-6.
  3. Hull PR and D'Arcy C. "Acne, depression, and suicide." Clinics in Dermatology. 2005; 23(4): 665-74.
  4. Magin P, Pond D and Smith W. "Isotretinoin, depression and suicide: a review of the evidence." British Journal of General Practice. 2005; 55(511): 134-8.
  5. Kaymak Y, Taner E. and Taner Y. "Comparison of depression, anxiety and life quality in acne vulgaris partients who were treated with either isotretinoin or topical agents." International Journal of Dermatology. 2009; 48(1): 41-46.
  6. Sundstrom A, et al. "Association of suicide attempts with acne and treatment with isotretinoin: Retrospective Swedish cohort study." British Medical Journal. 2010 Nov. 11.
  7. Chia CY, et al. "Isotretinoin therapy and mood changes in adolescents with moderate to severe acne: a cohort study." Archives of Dermatology. 2005; 141(5): 557-60.
  8. Hersom K, et al. "Isotretinoin and antidepressant pharmacotherapy: a prescription sequence symmetry analysis." Journal of the American Academy of Dermatology. 2003; 49(3): 424-32.
  9. Ferahbas A, et al. "A pilot study evaluating anxiety and depressive scores in acne patients treated with isotretinoin." The Journal of Dermatological Treatment. 2004; 15(3): 153-7.
  10. O'Reilly KC, et al. "Chronic administration of 13-cis-retinoic acid increases depression-related behavior in mice." Neuropsychopharmacology. 2006; 31(9): 1919-27.
  11. Azoulay L, et al. "Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study." The Journal of Clinical Psychiatry. 2008; 69(4): 526-32.
  12. Yesilova Y, et al. “Effects of isotretinoin on obsessive compulsive symptoms, depression, and anxiety in patients with acne vulgaris.” Journal of Dermatological Treatment. 2012; 23(4): 268-71.
  13. Ergun T, et al. “Istotretinoin has no negative effect on attention, executive function and mood.” Journal of the European Academy of Dermatology and Venereology. 2012; 26(4): 431-9.
  14. Marron SE, Tomas-Aragones L and Boira S. “Anxiety, Depression, Quality of Life and Patient Satisfaction in Acne Patients Treated with Oral Isotretinoin.” Acta-Dermato-Venereologica. 2013; [ahead of print].
  15. Nevoralova Z and Dvorakova D. “Mood changes, depression and suicide risk during isotretinoin treatment: a prospective study.” International Journal of Dermatology. 2013; 52(2): 163-8.
  16. Yesilova Y, et al. “Effects of isotretinoin on social anxiety and quality of life in patients with acne vulgaris: a prospective trial.” Acta-Dermato-Venereologica. 2012; 20(2): 80-3.
  17. Cohen J, Adams S and Patten S. "No association found between patients receiving isotretinoin for acne and the development of depression in a Canadian prospective cohort." The Canadian Journal of Clinical Pharmacology. 2007; 14(2): e227-33.
  18. Wysowski DK, Pitts M and Beitz J. "Depression and suicide in patients treated with isotretinoin [letter]." The New England Journal of Medicine. 2001; 344: 460.
  19. Marqueling AL and Zane LT. "Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review." Seminars in Cutaneous Medicine and Surgery. 2005; 24(2): 92-102.
  20. Wysowski DK and Beitz J. "Methodological limitations of the study "isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide." Archives of Dermatology. 2001; 137(8): 1102-3.
  21. Strahan JE and Raimer S. "Isotretinoin and the controversy of psychiatric adverse events." International Journal of Dermatology. 2006; 45(7): 789-99.
  22. Wysowski DK, Pitts M and Beitz J. "An analysis of reports of depression and suicide in patients treated with isotretinoin." Journal of the American Academy of Dermatology. 2001; 45(4): 515-9.
  23. Wolverton SE and Harper JC. “Important controversies associated with isotretinoin therapy for acne.” American Journal of Clinical Dermatology. 2013; 14(2): 71-6.
  24. Misery L, et al. “[Isotretinoin and adolescent depression].” Annales de Dermatologie et de Venereologie. 2012; 139(2): 118-23.
  25. Thiboutot D and Zaenglein A. “Isotretinoin and affective disorders: thirty years later.” Journal of The American Academy of Dermatology. 2013; 68(4): 675-6.

Because isotretinoin as a molecule dissolves best in fat, it is essential that you take it with a meal that contains an adequate amount of dietary fat. 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.”1 This failure to take Accutane with meals may account for some of the relapse that we see post-Accutane.

So what kind of meal should you eat 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, 6 ounces of apple juice, and 1 donut), and found that this was also enough to approximately double the absorption rate.3 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 Accutane 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 you take your Accutane pill.

One exception – Absorica™: In 2012, the FDA approved a new version of isotretinoin for sale in the U.S. that is marketed under the brand name Absorica™. 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.4 While data does show that Absorica is absorbed significantly more than regular isotretinoin on an empty stomach, the claim that Absorica can be dosed without regard to meals may be slightly skewed, since data shows that even with Absorica, the amount of isotretinoin in the blood remains significantly higher when taken with a high-fat meal. Thus, it may also be prudent to take Absorica with a meal which contains an adequate amount of dietary fat.


  1. Roche Laboratories, Inc. (2006/8). accutane (isotretinoin) capsule, liquid filled. Available: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=8655#section-13. Last accessed 16th Jan 2014.
  2. Colburn WA, et al. “Food Increases the Bioavailability of Isotretinoin.” Journal of Clinical Pharmacology. 1983; 23: 534-539.
  3. Webster GF, et al. “Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: A randomized, 4-treatment, crossover study.” Journal of the American Academy of Dermatology. 2013; 69(5): 762-7.
  4. ABSORICA [prescribing information]. Jacksonville, FL: Ranbaxy Laboratories Inc; May 2012.

The birth defects caused by Accutane are devastating and life threatening. Birth defects include skull, ear, eye, facial, central nervous system, cardiovascular, thymus, parathyroid abnormalities, and death.3 Clinical research shows extremely high risk for birth defects in pregnant women.4 The effects and risks of Accutane on unborn children are so severe that female patients of childbearing age are required to use two (2) forms of birth control while on Accutane.5

Pregnancy control

The iPLEDGE program was launched in March 2006 to prevent women from becoming pregnant while on Accutane.5-6

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

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.

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.1

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.

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."

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

 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. 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 side effects included severely dry lips, extremely dry skin, dry eyes and sometimes severe joint pain. Since Accutane, whenever I sprint or exert myself in quick bursts my joints react with inflammation. Whether this is coincidence or the result of Accutane is unclear. My acne relapsed post-Accutane to what I would describe as moderate acne. I am now able to control my acne symptoms with The Regimen."