Behind the Scenes of Isotretinoin: My Journey and Recommendations

Abstract

Isotretinoin is a form of Vitamin A used in treatment of severe, refractory acne vulgaris with treatment duration ranging anywhere from 3 to 12 months. The side effects of isotretinoin require monthly dermatologist visits and utilize a risk-management program called iPLEDGE REMS run by the Federal Drug Administration (FDA), which verifies that patients are not pregnant while starting or while taking isotretinoin. The physical and mental side effects experienced on isotretinoin are unique to each patient and can be severely debilitating. My own experience taking isotretinoin for 8 months was filled with multiple unexpected side effects that affected both my physical and mental health. As a result, I strongly believe dermatologists should help patients in analyzing the risk versus benefit profile of isotretinoin, present all other options, and ultimately emphasize patient-provider shared-decision making. Furthermore, at monthly visits dermatologists should be required to implement open dialogue regarding side effects to avoid patient feelings of fear and shame. Additionally, the iPLEDGE REMS system should consider creating a systematic documentation of symptoms to help normalize experiences and guide treatment plans.

Introduction to the Issue

For many people, oral isotretinoin, commonly known its brand name Accutane, is a life-changing drug that finally forces one's acne into remission. Isotretinoin is used to treat severe, recalcitrant cystic and nodular acne that is often refractory to other treatment methods. Providing this drug safely to patients requires lab monitoring, monthly visits with a dermatologist, and participation in a national risk-management program. Furthermore, certain diagnoses that affect the immune system, allergies, and pregnancy and peripartum states are all potential contraindications to use. Other medications, supplements, vitamins, etc that a patient is on must also be taken into consideration. As a result, dermatologists are supposed to make patients aware of all potential risks and benefits to help support them making an educated decision.

The national iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) system is run by the Federal Drug Administration (FDA) in the United States and is used to ensure patients are not pregnant before starting and while on isotretinoin. This is due to the known teratogenic side effects of severe birth defects, miscarriage, and stillbirth if a patient is pregnant while on this medication. ¹ Therefore, patients who can become pregnant are required to take 2 pregnancy tests before starting the medication and another test each month while on the medication. Additionally, patients must agree to use and document 2 firms of birth control and complete a monthly quiz to establish eligibility for obtaining their medication. The iPLEDGE quiz asks questions regarding ways one can become pregnant, how to correctly use birth control methods, and to verify that the patient is not sharing their medication. ² After completion, the medication must be approved by the dermatologist after each monthly visit at which point it is successfully sent to the pharmacy and a 7-day pickup window is initiated. The clinical guidelines to utilize iPLEDGE have existed for years, yet they fail to acknowledge other aspects of how a patient's life can be affected by this drug. This system does not include any documentation of mental or physical side effects or symptoms and does not have a space to ask any questions.

The known side effects of isotretinoin include whole-body dryness potentially involving the skin, lips, nose, eyes, and mouth alongside sun-sensitivity. Furthermore, acne can potentially worsen at first prior to it improving. Other common reported side effects include affecting eyesight, hair, muscles, joints, stomach problems, and altered cholesterol and triglyceride levels. ² Very uncommon side effects include increased pressure on the brain and liver damage. There have also been reports of depression, thoughts of committing suicide, and inflammatory bowel disease from isotretinoin.

Literature regarding a patient's quality of life while taking this drug is not novel with multiple scoring systems and retrospective reviews looking at large patient cohorts. ³ However, what is rarer and less commonly discussed are first-hand accounts of a consumer's perspective in a qualitative format that is not grouped alongside others. ⁴ Understanding an individual patient's experiences and recommendations with this drug will hopefully translate to better patient education, shared-decision making, and aligned goals of care.

I was 22 years old and in my second year of medical school when my dermatologist and I accepted failure from all other treatments, and my 8-month journey with isotretinoin began. I was briefed on symptoms that would necessitate immediate discontinuation: vision changes, right upper quadrant pain, red urine, and severe headaches. After undergoing mandatory initial blood draws, 2 negative pregnancy tests and completing the iPLEDGE quiz, I finally received my first month's supply. I then briefly looked through the dense pamphlet that outlined the variety of potential side effects. Despite this list of side effects and potential complications, I felt assured that none could be worse than the acne that had dictated my life since sixth grade.

During the first month on isotretinoin, I noticed minor changes: drier lips requiring more Aquaphor, and achy leg muscles after climbing to my third-floor walkup apartment. These were annoying inconveniences, but it was all manageable. My second month's labs results revealed cholesterol and triglyceride levels resembling those of a 65-year-old smoker. Subsequently, I began experiencing knee and back pain during my normal low-intensity workouts. I stopped working out as much as a result and realized I gained 10 pounds and felt more sluggish. I noticed my hair thinning, my normal braid felt half as thick as before. I woke up each morning desperately reaching for eyedrops so my dry eyes could open comfortably. Trading a shiny forehead by 11am for low back pain by 2pm didn’t feel like a victory. I started to feel more anxious and would often dread taking my evening dose. I started feeling defeated. How could the drug meant to cure my problem of acne start causing so many new ones?

Key Factors for Consideration

As a medical student, I delved into existing literature on isotretinoin's side effects. While the well-known physical side effects had been discussed, the potential psychiatric effects were not emphasized. I started to grow uncertain if my new depressive mood and heightened anxiety were potentially linked to my medication. I was grateful to never have any suicidal thoughts, but the physical and mental toll made daily tasks increasingly challenging. Concerns about long-term side effects mounted, but fear and embarrassment prevented me from sharing these thoughts with my dermatologist. I was done with 5 months of treatment and kept convincing myself I could make it through another 3. I was scared there would be no other solution to my acne, but it felt like I was substituting one plague for another.

The questions I was asked every visit consisted of contraception methods, suicidal thoughts, and verifying that I was not sharing my medication. I was never once asked if I wanted to continue the drug or how it was affecting my quality of life. I understood my provider's busy schedule and patients with more severe conditions and this made me shy away from understanding what would happen with discontinuation. Eventually, I persisted and completed my isotretinoin course with immense relief. I was excited for my skin to be the clearest it had ever been, but I was more eager for my mind and body to return to their pre-isotretinoin state. The myalgias, arthralgias, and severe headaches notably resolved. But even a full year after my last dose, the dry eyes and thinning hair persist. While my personal experience is the example of one person and cannot be generalized to every situation, discussing with peers who similarly were on isotretinoin helps me realize that this experience can be shared by others and demands improvement for better patient outcomes.

Current literature has examined patient comprehension and comfortability with their dermatologists and with the iPLEDGE system and has produced mixed results. In comparison to the traditional iPLEDGE system, a mandatory informational video was seen to be successful in improving patient understanding regarding how iPLEDGE worked and the risks of isotretinoin. ⁵ Other research supports how iPLEDGE can sometimes create information overload in a less digestible manner which can lead to worse outcomes, which again supports a more one-on-one discussion between patient and physician instead of through a website. ⁶ Overall, this supports the key considerations that dermatologists must consider to help patients have better experiences while taking isotretinoin.

Recommendations

My story with isotretinoin mirrors the experiences of many. As both a patient and future healthcare provider, I’m motivated to share my perspective to bridge gaps and advocate for genuine patient support. The diverse range of experiences that isotretinoin-users undergo underscores the importance of thorough provider-patient communication. Patients must be provided with comprehensive information on the range of ways isotretinoin might affect the body and mind. This information should be communicated sensitively and personally as to inform patients without inducing fear. Furthermore, dermatologists should include teach-back techniques to ensure adequate patient education. ⁷ Discussing the risk versus benefit for each patient can help avoid the online searching for answers and resultant anxiety induced in patients. While confirming contraception and possession of the medication is needed for the national iPLEDGE system, these should not be the only questions asked at each monthly visit.

In hindsight, I wish I felt more confident in wanting to bring up the debilitating yet manageable symptoms that affected my day-to-day life. Perhaps in doing so, my dermatologist and I could have considered other medications or a lower dose with longer course time if I even knew of these to be options. Even as a medical student who has some baseline knowledge of drug side effects, I still felt afraid that bringing up these concerns would mean drug discontinuation and loss of all progress. I would have loved the opportunity to be asked what side effects I am experiencing and being reassured that other options and ways to address them exist.

Dermatologists must better support the potential psychological aspects of this medication and offer appropriate referrals for counseling or psychiatric services as needed. ⁸ The existing qualitative research data of isotretinoin supports enough concern for establishing mental health baseline and check ins. ⁹ Therefore, a psychological screening prior to starting medication should be instituted to establish a baseline, similar to the mandated lab work and pregnancy tests. Many teenage patients using this medication already suffer from mental health conditions such as depression and anxiety. ¹⁰ Worsening of these conditions on this medication can create further mental and physical harm for young patients. Future efforts such as integrating both physical and mental side effects questions into the mandatory iPLEDGE quizzes prior to drug initiation and as part of the monthly visits would help patients have the opportunity to discuss their potential concerns. Eventually, research investigating this potential integration would help identify if it is in fact a successful effort in helping maintain patient quality of life while on isotretinoin and would be a major step in the right direction.

Conclusion

Overall, the nuanced, individualized experiences on isotretinoin demand a patient-centered support system that encourages healthy discussion and fosters shared decision regarding treatment continuation.