Accutane - Isotretinoin

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) which is administered orally in pill form, normally for 15-20 weeks (3.5-4.5 months).¹ It was originally prescribed for people with severe acne that did not respond to other treatments,² but has gained in popularity in the past 25 years and is prescribed more and more frequently for less severe acne.^3-5 This practice is controversial because Accutane is a serious medication and causes side effects which can be as devastating as they are widespread. Accutane need not be paired with other medications.⁶

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%).^7-8
2. Acne bacteria (P. acnes) live in skin oil. Since oil is dramatically reduced, so is the amount of acne bacteria in the skin.⁸
3. It slows down how fast the skin produces skin cells inside the pore, which helps pores from becoming clogged in the first place.⁹
4. It has anti-inflammatory properties.⁹

Although acne may get worse within the first month of Accutane use for about 30% of patients, the ultimate results are usually dramatic.¹⁰ 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.¹¹ 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.^6,8,11-15 This relapse rate is dose-dependent.¹² 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.¹⁴

Low and intermittent dosing: Researchers have published two 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 only about 75% of the usual Accutane dose, and thus suffer less side effects.^16-17 Intermittent dosing (taking Accutane only 1 week of every month) appears to work less well, producing inadequate results for more than half of the patients studied.¹⁷

• Hair/Skin/Nails
• Organs
• Reproductive
• Muscular/Skeletal
• Nervous
• Digestive
• Circulatory

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, and relative risk estimates, performed in the United States, the UK, and Canada.^3-11 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.^7-9,12 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.¹³

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.^14-15 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."¹⁶

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 Two recent studies, one small American study and one large Swedish study, again showed no connection.^5-6

The preponderance of the evidence at this point is that Accutane does not appear to be linked with suicide and depression. However, to be safe, it is important for anyone taking Accutane to closely monitor their mental health while on the drug.^1,4,17 If you find yourself feeling depressed or suicidal, seek help right away.

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."

Dan Kern
Acne.org Founder

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, albeit not to the degree it was before my Accutane cycle. I am now able to control my acne symptoms with The Regimen."

Dan Kern
Acne.org Founder