Accutane® – in-Depth

The use of Accutane® for acne has become highly controversial, and for very good reasons, but in the beginning it seemed like the answer to every acne sufferer’s prayers.

After the initial success of topical retinoids in the late 1970’s, the scientists at Hoffman-LaRoche, (the manufacturer of Johnson and Johnson’s Retin A®) began investigating a related chemical compound of retinoic acid (topical retinoid) called 13-cis-retinoic acid, or isotretinoin. When taken internally, isotretinoin causes the sebaceous glands to stop producing oil, making the skin very dry.

Studies of 13-cis-retinoic acid at the National Institute of Health by Dr. Gary Peck in 1979, and by Dr. Gerd Plewig in 1980 in Munich, Germany, showed amazing results. These studies were done on severe cystic acne patients who had responded to no other treatments. Of the fewer than 100 patients in the studies, virtually everyone’s acne went into remission while on the drug, and the majority stayed in remission in the 20 months following the test.

Accutane® approved by FDA

Physicians and acne sufferers alike waited impatiently for the FDA to complete its three year review of the drug, and in 1982 Hoffman-LaRoche (often referred to simply as Roche) began marketing isotretinoin as Accutane®.

The following year Dr. Peck was awarded the Inventor’s Award by the US Department of Commerce, and a Meritorious Service Medal by the US Public Health Services. His work was seen as the biggest advancement in the entire history of acne treatment.

In February 2002, Roche’s patents for isotretinoin expired, and other pharmaceutical companies began marketing generic isotretinoin under various trade names: Amnesteem (Mylan), Claravis (Barr), Clarus (PremPharm), Decutan (Actavis), Isotane (Pacific Pharmaceuticals), Izotek (BlauFarma), Oratane (Genepharm Australasia), ISOTRET (Liva Healthcare Ltd.) or Sotret (Ranbaxy).

However, even in the beginning, Roche and the FDA knew there were problems with the drug and its administration. 30% of women who took Accutane® when they were pregnant gave birth to children with serious birth defects including mental retardation and physical malformation. The prescribing physicians were supposed to confirm that their women patients were not pregnant, but many physicians weren’t doing more than simply asking.

In response, in 1998 the FDA instituted restrictions on prescribing and dispensing the drug, first with the “System to Manage Accutane® Related Teratogenicity” (SMART) in 2000 (Teratogenicity is the ability to cause developmental anomalies, both physical and mental, in a fetus). The FDA tightened the restrictions with the iPLEDGE program in 2006. Since then, all patients, whether male or female, who use this drug, their parents if they are underage, all physicians who prescribe it, and all pharmacies that fill prescriptions for it, must sign this complicated, frightening, FDA mandated pledge. Still, a retrospective cohort study recently found that pregnancy rates were quite high during the period (1 per 30 women per year), and 84% of pregnancies were ended by induced abortions. This is a travesty of health care.

The other side effects of Accutane® were serious enough that the drug was never supposed to be prescribed except in the most severe, unresponsive, cases of acne. But many acne sufferers wanted to simply be able to take a pill and be “cured” so pressured their doctors into prescribing isotretinoin. Some physicians to this day are unaware of the seriousness of the side effects, and prescribe the drug far more casually than was ever intended.

By systemically shutting down the body’s ability to produce sebum, isotretinoin affects other areas besides the skin. It affects essentially all the epithelial tissues of the body, causing them to become quite dry, and compromising their function. Epithelial tissues are the lining tissues of the body, both its surface and its internal organs. This includes not only the skin, hair and nails, but the mucus membranes, the lining of the lungs and the digestive track including the pancreas, kidneys and liver, the reproductive organs and the elimination track. It affects your ability to produce tears and spit. Just think what compromising all those physical functions can do to the body, and you will be a long way towards predicting the side effects of isotretinoin.

Long-term effects from Accutane® unknown

The list of what isotretinoin can do to you is long and scary. Clearly, it doesn’t do all these things to everyone who takes it, but it does do some of them to everyone, and each of them to at least some people. The most frightening part is that many of the effects take years to manifest. As the first patients to use Accutane® were teenagers in the 1980s, those first users are only in their forties and fifties now, so some of the long term effects have still to develop.

But here is what we know so far it can do, in addition to the birth defects discussed above:

Isotretinoin will cause uncomfortable dryness of skin, lips, hair, cuticles, eyes, and mucous membranes, which can lead to infection in all those areas, including conjunctivitis and cheilitis (acute inflammation of the lips).

It can cause the

  • reduced ability to tolerate contact lenses,
  • itching,
  • rosacea,
  • permanent thinning of the skin,
  • permanent skin fragility,
  • rashes,
  • temporary and permanent hair loss,
  • liver damage,
  • kidney malfunction,
  • elevated blood lipids (cholesterol and triglycerides),
  • headaches,
  • back pain,
  • fatigue,
  • joint pain,
  • problems regulating blood glucose levels,
  • decreased libido,
  • erectile dysfunction,
  • cataracts,
  • optic neuritis,
  • papilledema (swelling of the optic disc which can lead to vision loss),
  • impaired night vision,
  • corneal opacities,
  • inflammatory bowel disease,
  • pancreatitis,
  • hepatitis,
  • osteoporosis,
  • degenerative disc disease and
  • interrupted bone growth.

The FDA’s medication guide for Accutane® says “Accutane® may stop long bone growth in teenagers who are still growing”. Several independent reports have stated that spontaneous premature epiphyseal (the structure that makes long bones grow long) closure can occur in acne patients receiving recommended doses of Accutane®. Since bone growth completes at a range of ages (17–20 years for upper limbs, 18–23 years for lower limbs) and since many acne patients are prescribed Accutane® in their late teens, when growth still occurs but has begun to slow down, there is a risk of people being affected without realizing it.

Isotretinoin interferes with the skin enzyme collagenase, leading to increased risk of severe scarring from procedures like dermabrasion, deep chemical peels, laser resurfacing and other facial surgeries.

Several scientific studies have posited that isotretinoin is a possible cause of Crohn’s Disease (a chronic inflammatory disease of the gastrointestinal track) and ulcerative colitis in some individuals. Three cases in the United States have gone to trial thus far, with all three resulting in multi-million dollar judgments against the makers of isotretinoin; there are an additional 425 cases pending.

Since the 1980s, scientific research has suggested a relationship between isotretinoin administration and the onset of psychological symptoms including depression, thoughts of suicide and psychosis. However, there are also studies arguing that there is no evidence of such a link. Patients with severe acne frequently show signs of clinical depression due to the condition. One study showed patients treated with isotretinoin experienced an average 21% decrease in frontal cortex functioning, a sign of potential depression, but the patients did not score high on the Hamilton Depression Rating Scale, a questionnaire designed to rate patients perceived level of depression.

Spontaneous suicides (suicides where the victim exhibited no signs of clinical depression) of Accutane® users have been reported. These reports may mean that Accutane® may cause users to make irrational decisions, and the brain to undergo something disruptive other than clinical depression.

Isotretinoin should not be used concurrently with tetracycline antibiotics, vitamin A supplements or methotrexate, a drug used in the treatment of cancer, autoimmune diseases and to medically induce abortions. When used with tetracycline it significantly increases the risk of “idiopathic (we don’t know what causes it) intracranial (within the scull) hypertension (high blood pressure)” or pressure around the brain. When used with vitamin A supplements, it can cause vitamin A toxicity. When used with methotrexate it increased the risk of hepatoxicity, chemical-driven liver damage.

Accutane® discontinued in US

On June 29, 2009, Hoffman LaRoche officially discontinued both the manufacture and distribution of their Accutane® brand in the United States due to what the company described as business reasons related to low market share (below 5%) coupled with the high cost of defending personal-injury lawsuits brought by patients who had been prescribed the drug. Generic isotretinoin is still available in the US through various manufacturers. Roche continues to defend Accutane® and claims to have treated over 13 million patients since its introduction in 1982. Hoffmann-La Roche will continue to manufacture and distribute Roaccutane outside the US.

As long as some acne sufferers still want so desperately to be able to just take a pill and have their acne go away, sales of isotretinoin will continue. But sadly, not only is it so potentially dangerous, it simply doesn’t work for all types of acne. Tens of thousands of Accutane® users were put at risk only to have their acne return after sometimes multiple courses of the drug.

There is no magic pill for acne, but there are safe, effective remedies. At The Acne Treatment Center, we’ll work with you every step of the way until you achieve a clear, healthy complexion without exposing you to any dangerous side effects.

©2011 Jane Neville Dudik, The Acne Treatment Center,