Accutane® Myths

Myths of Isotretinoin (Accutane®) Therapy in Patients with Acne

Patients with acne are treated with a variety of medications.  Isotretinoin, for the treatment of acne, has been used since 1982.  Since the FDA’s approval of isotretinoin, greater than 13 million people worldwide have been successfully treated (Roche, unpublished data).  Isotretinoin is the most effective treatment for severe inflammatory acne and failure to prescribe it can lead to severe scarring, cosmetic disfigurement, and detrimental emotional impact for the patient.  The most common side effects include dry lips and skin.  Over the years, the prescribing of isotretinoin has become more cumbersome due to the teratogenic nature of this drug.  Despite the extensive clinical experience with isotretinoin and the vast amounts of relevant scientific literature, many practitioners still believe that the drug is excessively dangerous.  The decision to withhold isotretinoin from a patient with inflammatory acne is not always based on scientific evidence; rather, it seems to be based on its own mythology.  The following are five myths associated with the use of isotretinoin as a treatment for acne.

Myth 1: Isotretinoin causes liver damage.

Review of the literature fails to show any reports that isotretinoin has induced hepatitis or liver failure.  In 1993 Bart and colleagues were the first to conclude that there is no evidence to support routine monitoring of liver function.  Recently, we have summarized our clinical and laboratory experience with 906 patients treated with isotretinoin.  No pathological changes in liver enzymes were found.  In our experience with treating more than 5,000 patients with isotretinoin, there are rare transient, insignificant elevations of AST, ALT, and Gamma-GT enzymes, which return to normal values even without withdrawal of the drug.

Myth 2: Isotretinoin causes elevation of plasma lipids, thus it is mandatory to monitor their levels during treatment.

The elevations of plasma cholesterol and triglyceride levels have two impacts on health: accelerating atherosclerotic disease, and inducing eruptive xanthomas or acute pancreatitis with high levels of triglycerides.  It is well established that isotretinoin increases the levels of cholesterol and triglycerides in 25% of the patients.  The second myth is based on early reports from the beginning of the 1980s studying very small groups of patients.  Zech and colleagues studied 20 patients treated with 2 mg/kg per day of isotretinoin.  They concluded based on this very small group and high dosage of isotretinoin that chronic increase in plasma lipids predisposes subjects to premature arteriosclerosis.  In 1985, Bershad et al. studied 60 patients treated with isotretinoin.  17% of the patients showed elevations of triglycerides, cholesterol, and LDL cholesterol.  They concluded that if the changes in plasma lipids persisted over a long period of time (no explanation was given as to what would be considered a “long period”), it might increase the risk of cardiac disease.  To our knowledge, there is no published evidence that an elevation in plasma lipid levels to the extent occurring in patients treated with isotretinoin for a period of 5 months increases the risk of atherosclerotic disease.  Moreover, a recently published study concluded that in young and healthy individuals treated with isotretinoin, significant variations in lipid levels do not influence the overall risk for cardiovascular disease.  What about the risk of pancreatitis in patients treated with isotretinoin?  The levels of triglycerides rarely exceed 600 mg/dL.  It is also not clear in the literature whether high triglyceride levels (more than 1000 mg/dL) are the actual cause for pancreatitis.

Myth 3: Isotretinoin causes photosensitivity, thus patients should not be treated in the summer.

We have treated more than 5,000 patients with isotretinoin during all seasons of the year in a “sunshine state” and with no preference to the winter.  We have not seen any case of photosensitivity to the drug, nor have we found published data supporting this phenomenon.  Thinning of the horny layer caused by isotretinoin is the reason for increased sensitivity to ultraviolet rays.  However, no phototoxic or photoallergic reactions are caused by the drug.

Myth 4: Isotretinoin should be given only for severe acne.

Some practitioners believe that isotretinoin treatment should only be reserved for patients with severe cystic acne.  This attitude is based on two points: that the medication is very expensive, and that the written indication given by Roche is severe cystic acne.  In the last several years many authors have shown that isotretinoin has been used for moderate acne, any acne with scarring, and post-adolescent acne.  In a survey done in seven countries, isotretinoin has been used for mild to moderate acne in 45% of the patients.  In regard to the cost-effectiveness of isotretinoin, it has been shown that where it is clinically indicated, the sooner therapy is initiated, the more cost-effective the outcome will be.  If isotretinoin is given for moderate to severe acne, then the cost of the treatment is significantly reduced in the longer term when compared with chronic oral antibiotic treatment.  A recent article published on behalf of the Australian Roaccutane advisory board concluded that any patient that shows scarring or marked psychological distress should be prescribed isotretinoin.

Myth 5: Isotretinoin causes depression and suicide attempts.

In recent years, there has been a growing interest in the possible relationship between isotretinoin use and increased risk of depression and suicide.  Although a casual relationship may exist between isotretinoin and psychiatric illness in adolescents and young adults, this has not been demonstrated in the literature.  Most of the articles do not show direct relationships between the two.  A study done by Jick et al. provided no evidence that the use of isotretinoin is associated with an increased risk for depression, suicide, or other psychiatric disorders.  A recent article did not support an association between the use of isotretinoin and the onset of depression.  We must not forget that acne appears to be a condition which has the potential to damage, perhaps even in the long term, the emotional functioning of some patients.  Evidence suggests a relationship between isotretinoin and depression needs to be weighed against the increasing prevalence of depression among adolescents and young adults and the psychological impact of acne.

Summary

Isotretinoin is currently the most effective therapy for inflammatory acne.  Due to its teratogenic effect, preventing pregnancy during treatment is essential.  Healthy patients using isotretinoin, can feel confident and reassured that it is the best treatment to reduce oil production and prevent the formation of comedones which are the main causes of acne.  Acne is a treatable condition, and any form of acne that can cause scarring or psychological impairment should be treated with isotretinoin.

References

1. Joseph Alcalay, M.D.

Journal of Drugs in Dermatology, 2004; 3(2): 179-182