Accutane Case Study

Introduction
When Accutane became available to consumers in 1982 as a treatment for recalcitrant nodular acne, it was regarded as a wonder drug. Researchers began investigating the risks of the medication only after news of adverse effects were reported to the Food and Drug Administration (FDA). Although Accutane has the ability to resolve persistent acne, the known side effects are of great importance to the consumer. Several studies have been conducted to elucidate the adverse effects of Accutane, as well as studies to show the medication’s efficacy and success rates. Accutane has high success rates in the cure of acne, with low recurrence rates. However, there are several adverse effects that every patient must be made aware of before they

begin treatment with Accutane. A question that has been raised for years since Accutane became available to consumers is whether the benefits of the medication outweigh the risks.
Discussion
Acne vulgaris is a common cutaneous disorder affecting adolescents and young adults (Thiboutot & Zaenglein, 2014). It is estimated that the prevalence of acne in adolescents is between 35-90% and typically resolves in the third decade of life. However, some individuals do not see complete resolution, while others develop acne in adulthood. Acne vulgaris is a disease of the pilosebaceous follicles with four major components including, follicular hyperkeratinization, increased sebum production, inflammation, and colonization of the follicle with Propionibacterium acnes. Acne lesions consist of open comedones (blackheads), closed comedones (whiteheads or pustules), and follicular cysts. When a follicular cyst ruptures, it contributes to the development of inflammation and the formation of papules and/or nodules. Inflammation and acne breakouts can also be caused by stress, elevated body mass index (BMI), diet, excess androgens that stimulate the production of sebum, and external factors such as soaps and detergents.
Acne can have significant psychological effects, including embarrassment, low self esteem, anxiety, and depression (Graber, 2015). Physical effects such as post inflammatory hyperpigmentation and permanent scarring frequently occur. Acne is one of the more common reasons individuals seek medical treatment from a dermatologist. Conventional therapies to treat acne include topical benzoyl peroxide, topical salicylic acid, topical antibiotics, topical retinoids, and oral antibiotics. The systemic retinoid, isotretinoin, also known as Accutane, is reserved for patients with severe recalcitrant nodular acne and/or when conventional therapies to treat acne fail to work. Accutane’s method of action reverses the pathogenic factors that cause acne (Owen, 2015). It shrinks the sebaceous glands, leading to a decrease in sebum. The reduction in oil inhibits the proliferation of P. acnes, which is a large contributor to the inflammatory process of acne. Accutane also normalizes desquamation within the follicle which regulates hyperkeratinization.
According to a study on the efficacy, safety and tolerability of oral isotretinoin conducted by Rajput and Saphale (2014), Accutane is an “effective and safe” treatment for the inflammatory lesions of acne vulgaris.

In their study, 40 patients were administered oral isotretinoin and were followed throughout their five month treatment. Prior to beginning treatment, comedogenic and inflammatory lesions were counted and recorded as baseline. At one, two and five months the acne lesions were recounted. By month one there was a 50% decrease of inflammatory lesions, and at the end of month two, there was a 50% decrease in comedones. Total improvement of inflammatory lesions was 86.12% at the end of treatment. 39.74% of the treatment group experienced excellent results, which is considered 80-100% resolution of total lesions. 55.27% of patients experienced good results, which is resolution of 50-79% of total lesions. With 95% of the treatment group experiencing good to excellent results, the researchers were able to prove statistically that these results are significant. While all of the patients saw improvement in their acne vulgaris, some did experience side effects. The most commonly reported adverse effects were scaling of the face (11%) and chelitis (5%). Other side effects experienced in this study include dryness, palmo-plantar peeling, and photosensitivity. Systemic side effects experienced by 5% of the patients were nausea, diarrhea and abdominal pain. None of the patients experiencing side effects required discontinuation of the medication and effects were treated

symptomatically.
Similar side effects were reported in a study conducted by Parinith, et al. (2014) on the safety and efficacy of low-dose isotretinoin in the treatment of acne vulgaris. 50 participants were administered isotretinoin for a total of three months and were then followed for six months after completion of the medication. Prior to administration of oral isotretinoin, each patient’s acne was graded 0-4 based on the severity, with 32% having grade 4, 56% having grade 3, and 12% having grade 2. This study required patients to have pre-treatment blood work drawn to document complete blood count, liver function tests, and lipid profile. At the end of treatment blood was drawn again. Of the 50 participants included in the study, 49 experienced chelitis and 42 reported xerosis. Dandruff, dry mouth, facial redness, hair loss and headache were also reported, but not nearly as frequent as xerosis and chelitis. Three participants each were documented having abnormal levels of total cholesterol and serum triglycerides, and abnormal levels of liver enzymes. At the end of the 12 weeks, 6% of patients had 100% clearance, now considered grade 0 acne. 90% of patients had greater than 75% clearance, putting them in the grade 1 category. Lastly, 4% of patients saw 50-75% clearance, lowering their acne score to grade 2. Parinith, et al. (2014) study concluded that low-dose isotretinoin was “effective in the treatment of moderate to severe acne vulgaris. The benefits … outweigh the risks…with a low incidence of severe side effects.”
Although not elucidated in the studies conducted by Rajput & Saphale (2014), and Parinith, et al. (2014), The iPLEGDE Program (2012) lists depression, psychosis and as possible side effects of oral isotretinoin. The evidence for making these claims comes from case reports, as discussed by Magin, Pond and Smith (2004). Between 1982 and 2000 the FDA received 394 reports of depression and 37 reports of suicide in patients that were taking oral isotretinoin. In 25 of the cases reported to the FDA, resolution of the mood disturbance was observed after cessation of the medication. If treatment was started again, depression often recurred. However, other case reports have suggested depression as a sequel of acne. Magin, Pond & Smith (2014) state acne has been associated with depression, anxiety, and suicidal ideation, on the basis that the disease itself causes low self esteem and self-consciousness. When an analysis was conducted on the sequence in which prescriptions for isotretinoin and antidepressant medication were written (which prescription was written first), no correlation between the use of isotretinoin and the onset of depression was demonstrated (Hersom, et al., 2003). Although a direct correlation between oral isotretinoin and depression cannot be made, this information should be used as a tool when a patient comes to a medical professional for the treatment of acne. A simple questionnaire to screen for pre-existing depression prior to the administration of oral isotretinoin could help to decrease the number of patients that report depression or suicidal ideations while receiving treatment for their acne.
Arguably the most serious side effect of oral isotretinoin is that it is a known teratogen (Owen, 2015). If a female were to get pregnant while taking Accutane, there is a very high chance of birth defects in the unborn baby, and spontaneous abortion. Documented abnormalities include defects of the face, eyes, ears, skull, central nervous system, cardiovascular system, thymus and parathyroid glands. Mental retardation is common as well. To decrease the rate of pregnancy during treatment with Accutane, in 2006 the FDA established The iPLEDGE Program, a computer based risk management program. Prior to beginning Accutane, female patients are required to commit to the use of two forms of birth control throughout treatment, as well as receive monthly pregnancy tests before a new monthly prescription can be obtained from the pharmacy (iPLEDGE, 2012). Signed consent forms confirming that the patient understands all of the known risks and side effects of taking Accutane, and a signed form confirming that they are committed to the use of two forms of birth control if they are sexually active are submitted into the patients iPLEDGE account. The account is accessible by the patient, the prescribing provider, as well as the pharmacist. If at any time a patient thinks they could be pregnant or has a positive pregnancy test, they must immediately discontinue using Accutane to limit the exposure to the fetus.
Conclusion
All medications have the potential to cause adverse effects. Patient education on the disease process of acne vulgaris and the known side effects of Accutane is a powerful tool when prescribing this medication. Data should continue to be collected as adverse effects are reported, as well as reports of the success rates that Accutane is known to achieve. Additional studies could be conducted with larger numbers of patients to understand if certain symptoms affect a particular demographic more so than another. Despite the known side effects of oral isotretinoin, millions of patients are prescribed the medication for their severe acne vulgaris every year. The minor side effects of xerosis and chelitis improve shortly after the course of treatment is ended and patients who previously suffered from severe acne vulgaris are left with clear skin. If precautions are followed to prevent pregnancy and any symptoms of depression are brought to the attention of a medical professional immediately, this medication can be administered safely and effectively.