Isotretinoin ( Accutane) is Still Superior for Hard to Treat Acne

by

Michael H. Berkson, M.D.

Up until the early 1980’s, there was no reliably effective treatment for severe acne.  People with a variant called nodular ( sometimes incorrectly referred as “cystic”) acne often suffered in silence as they bore the shame of their disfiguring condition.  But the torture did not end when their breakouts finally abated, as significant physical and psychological scarring was a frequent sequelae of this type of acne.

The outlook for sufferers  of nodular acne brightened considerably when a drug called Accutane was introduced to the market in 1982.  For the first time, there was a highly effective treatment for severe acne, and cures were even being reported.  Accutane was rightfully being hailed as a miracle drug.  Accutane has most definitely stood the test of time and remains the single most effective treatment for severe acne, as well as some forms of less severe, but persistent acne.

Isotretinoin, or 13- cis-retinoic acid is the molecule that was originally sold under the brand name Accutane.  The Accutane brand was retired many years ago and isotretinoin is now made by several generic manufacturers and sold under the names  Amnesteem, Claravis  Myorisan, and the newer brand, Asorbica. The names are not important as each contains the same pharmacologically active ingredient, Isotretinoin, that was in the original Accutane.  For the purposes of this article, and in the name of simplicity and familiarity, all brands of isotretinoin will be referred to as Accutane.

Accutane is one of several oral retinoids.  Retinoids are a class of drug that is derived from vitamin A.  These particular molecules bind to specialized receptors in the cell nucleus called retinoic acid receptors resulting in multiple effects on cellular processes including cell growth and differentiation.

Unlike any other treatment, Accutane directly or indirectly acts on all of the four main factors that lead to the development of acne.  These four factors are: sebum( oil) production; comedogenesis, which is a plugging of the sebaceous follicle; proliferation of bacteria ( P.acnes) in the follicle; and inflammation. Most important is its ability to suppress sebum production. Accutane has a profound effect on the sebaceous glands such that sebum production practically grinds to a halt.  Without sebum, the P. acnes bacteria that colonize the sebaceous follicle have a hard time surviving. Less bacteria results in less inflammation. Less inflammation also leads to less comedogenesis.  Accutane also directly inhibits inflammation and comedogenesis.

The official indication for Accutane is severe nodular acne for which other treatments such as oral antibiotics are insufficient to control the breakouts. Any variant of acne that results in significant scarring is also a clear cut indication for Accutane.  With that said, many dermatologists use Accutane for milder acne that is persistent and cannot be contained without long term antibiotics. Because of the increasing issue of bacterial resistance to antibiotics, alternatives such as Accutane are being used more frequently.

Unlike other acne treatments which are usually carried out over an open ended period of time, a typical course of Accutane lasts about six months. Over that time, the vast majority of people will demonstrate marked to complete clearing of their acne. A significant proportion of those will remain acne free indefinitely after a single course of Accutane.  For those whose acne recurs, it tends to be less severe than before treatment with Accutane. Repeat treatment with Accutane, if necessary, is an option for some.

Accutane comes as a capsule which is taken once or twice daily.  It requires fat for absorption so it needs to be taken with a big meal or a concentrated source of fat such as a tablespoon of peanut butter.

One of the great things about Accutane is that it works by itself without the need to combine it with other topical or systemic treatments.  Most notice a decrease in their acne during the first several months, but some will see a temporary uptick in the frequency and intensity of breakouts.  In an effort to avoid early treatment flare ups, it is customary to start with a lower dose and work up to the target dose, which is calculated based on weight, over the course of a few months.  By the end of five or six months, most are having minimal to no breakouts. In the initial studies in the late 70’s that led to the approval of Accutane, the standard treatment course was arbitrarily set at 20 weeks.  Although five or six months of treatment is generally adequate for most people, some require more time to get to the desired endpoint of clear.

Despite its dramatic effectiveness, Accutane does have some downsides and should only be prescribed by practitioners who are familiar with and comfortable with its use.  There are some common side effects associated with Accutane, most of which fall under the category of nuisance problems. For instance,  practically everybody experiences dry skin and chapped lips.  Dry eyes and minor nosebleeds are also fairly common. Aches and pains in the muscles and joints sometimes occur, especially with strenuous physical activity.

A flare up of the acne early in the course of treatment was mentioned earlier, and if moderate, can be dealt with by reducing the dose of Accutane. For the unusual severe flare up, temporarily stopping treatment or adding oral steroids can be helpful.

About one in four patients develop elevated blood fats (triglycerides), and for this reason  blood work to check for elevated triglycerides and other lab abnormalities may be obtained near the beginning of treatment and possibly repeated several times during the treatment course. An occasional person will develop decreased night vision while on Accutane because of the vitamin A like effect on the retina.  For most, these side effects are not deal breakers and most would consider them to be a fair trade off for clear skin.

The biggest problem with Accutane is that it has a high probability of causing birth defects if a woman were to be or become pregnant while on Accutane. For this reason women of childbearing potential are required to use two forms of birth control, simultaneously, for one month before, during, and for a month after treatment. A baseline pregnancy test is obtained before starting treatment and monthly throughout the entire course.  Ipledge is a risk management program and registry that was developed primarily to reduce the pregnancies that were occurring among women on Accutane.  All Accutane patients and prescribers are required to register with Ipledge.

Finally there are a few controversies regarding a possible association between Accutane and mental health issues and inflammatory bowel disease.  There may be a small subset of individuals who are vulnerable to mood changes while on Accutane, specifically signs and symptoms of depression, aggressive behavior, and on rare occasion suicidal behavior.  There have been a number of studies that have looked at this association and found no causal link between Accutane use and mood disorders. Likewise, with inflammatory bowel disease- ulcerative colitis and Crohn’s disease-there has been no cause and effect relationship established to date.  Although a history of mood disorder or inflammatory bowel disease does not preclude the use of Accutane, it makes sense to exercise extra caution in these individuals.

In summary, the arrival of Accutane on the market represented a true breakthrough for people with severe acne, and it remains the single most effective treatment for all types of acne.  It can completely clear most people’s acne, and some can be considered to be cured after a single course of treatment. Most people do experience minor side effects while on Accutane, but for most they represent an inconvenience which is largely surmountable. Female patients need to carefully follow the Ipledge guidelines to ensure that they do not become pregnant while on treatment. Finally, Accutane can be a somewhat complicated drug to properly prescribe and those who feel that they might be candidates for treatment should consult with a dermatologist who is the health care specialist best equipped to use this remarkable medication in a safe and effective way.

The next article discusses procedural treatments for acne which can be used in certain situations to complement medical treatment.

References:

An Overview of Acne Therapy, Part 2: Hormonal Therapy and Isotretinoin.  Marson JW, Baldwin HE.  Dermatol Clin. 2019 Apr;37(2):195-203.

Efficacy and adverse events of oral isotretinoin for acne: a systematic review. Vallerand IA et al. Br J Dermatol. (2018)

Isotretinoin systemic therapy and the shadow cast upon dermatology’s downtrodden hero.  Lowenstein EB, Lowenstein EJ.  Clin Dermatol. 2011 Nov-Dec;29(6):652-61.

Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis. Huang YC et al. J Am Acad Dermatol. (2017)