What are the side effects of Accutane (isotretinoin)?
Accutane (isotretinoin) is a systemic medication and affects all parts of the body
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Article Summary
Isotretinoin, despite being an effective acne treatment, can have serious side effects. Side effects of the skin and mucous membranes are expected and treatable. However, because isotretinoin is an oral medication, it can affect the entire body, and some patients may experience more severe side effects elsewhere in the body, such as eye and vision problems, psychiatric symptoms, joint pain, problems with blood, intestinal disorders, and many others.
Most importantly, and most disastrous, is severe birth defects and spontaneous abortion. Isotretinoin is the #1 most birth-defect causing medication on the market. Women must absolutely avoid pregnancy since isotretinoin greatly increases the chance of birth defects.
If your doctor recommends isotretinoin, it is important to review your medical history with your doctor. Unless you are experiencing widespread, severe acne that is scarring, it is best to exhaust all other avenues of treatment before trying isotretinoin.
- Side Effects of the Skin, Mucous Membranes, and Eyes
- Other Side Effects
- Psychiatric Side Effects
- Long-term Side Effects
- What to Keep an Eye on While Taking Isotretinoin
- Drug Interactions
- Who Should Not Take Isotretinoin
Isotretinoin is a vitamin-A derivative that is normally taken for 15-20 weeks and results in long term remission of acne symptoms in up to 2/3 of people who take it. While results are impressive, the side effects of isotretinoin treatment are diverse and sometimes severe.
Isotretinoin causes severe birth defects and should be avoided in women who are pregnant or who may become pregnant.
Dryness of the skin, lips, nose, and mouth interior affects nearly all patients using isotretinoin, but these symptoms are treatable. Less common symptoms include the eyes dryness and irritation, liver problems, intestinal conditions, musculoskeletal disorders, and headaches. Isotretinoin also decreases production of pituitary hormones and increases triglyceride and cholesterol levels. Finally, isotretinoin's connection with depression and suicide is controversial, and there is no definitive proof connecting isotretinoin psychiatric conditions.
However, most researchers conclude that the majority of side effects are reversible in most cases.
Side Effects of the Skin, Mucous Membranes, and Eyes
The most common side effects of isotretinoin involve the skin, mucous membranes, and eyes.
Side effects of the skin and mucous membranes
Side effects of the skin and mucous membranes (membranes that line body cavities and secrete mucous) are common in patients treated with isotretinoin. The most common symptoms are itchiness and dry skin.1
Expand to read details of studies
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In an analysis published in 2001 in the Journal of the American Academy of Dermatology, McLane observed that over 90% of patients who experienced adverse side effects of the skin reported dry skin, localized exfoliation, rash, and dermatitis (a type of skin irritation).2
In a review published in the Expert Opinion on Drug Safety, Tripathi et al. reported that:
- 100% of patients experienced lip dryness
- 95% of patients experienced cheilitis (inflammation of the lips)
- 50% of patients experienced dryness of the nostrils
- 40% of patients experienced dryness of the oral mucosa (mucous membrane lining the inside of the mouth)3
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Side effects of the eyes
Side effects related to eye irritation may also include intolerance to contact lenses, increased S. aureus bacteria infections, and light sensitivity.3 Rare side effects include night vision disorders and corneal opacity (scarring or clouding of the cornea, the eye's outermost layer).1
Expand to read details of studies
In the Journal of the American Academy of Dermatology, McLane noted that dryness and irritation of the eyes occurs in 28% of patients taking isotretinoin.2
In a study published in the Archives of Dermatology, Neudorfer found that:
- 28% of patients experienced eye dryness and irritation
- 13.8% of patients experienced persistent adverse effects of the eyes after the end of treatment4
Neudorfer's findings also indicated that isotretinoin increased the risk of conjunctivitis (pink eye) by 1.7 times. Additionally, isotretinoin use was associated with an increased risk for developing hordeolum (painful bumps around the eyelid), chalazion (inflammatory lump near tear gland), and blepharitis (inflammation of the eyelid).4
Side Effects of the Skull/Head, Musculoskeletal System, Liver, Blood/Hormones, and Intestines
Other side effects of isotretinoin include headaches, musculoskeletal disorders like joint pain, liver problems, and potentially intestinal conditions.1
Expand to read details of studies
In a review published in Clinical Dermatology, Rigopoulos et al. notes that headaches are rare but might be due to intracranial hypertension, which is high pressure of the fluid surrounding the brain and spinal cord. About one third of isotretinoin patients can expect joint aches. Rigopoulos et al. also reported that hepatitis is a less common side effect. Inflammatory bowel disease is a rare side effect.1
Pituitary hormones control many processes in the body such as sleep cycles, metabolism, and sex hormone production. In a study published in Dermatology, Karadag et al. reported that isotretinoin decreased pituitary hormones in a dose-dependent way; in other words, the higher the dose, the lower the hormone levels.5
Isotretinoin treatment also affects blood cell counts, triglyceride (fat/lipid) levels, and cholesterol levels, summarized in the table below. However, it is worth noting that in a meta-analysis published in JAMA Dermatology, Lee et al. found that the proportion of patients with these abnormalities was low.6
| Blood Component | Findings |
|---|---|
| Triglyceride (fat/lipid) levels | In a review published in the Journal of the American Academy of Dermatology, Tripathi et al. reported research that demonstrated increased triglyceride levels in 60 patients. Triglyceride levels peaked at 4 weeks of therapy in men and at 12 weeks of therapy in women. 17% of patients showed abnormally high levels of triglyceride in the blood after 20 weeks of isotretinoin treatment.3 |
| Blood cell counts | Isotretinoin increases platelets and hemoglobin below in this section we only talk about lowered red blood cells and decreases red blood cells. In Scientific World Journal, Ataseven et al. published a study of 112 patients - 28 males and 84 females - whose blood cell counts were recorded before isotretinoin treatment and in the third month of isotretinoin treatment. Ataseven et al. recorded an increase in platelet density and a significant decrease in red blood cell count at three months of treatment, but no meaningful changes were observed for white blood cell (cells of the immune system).7 |
| Cholesterol | In the Journal of the American Academy of Dermatology, McLane reported that isotretinoin increases cholesterol by an average of 14% but these values remain within normal levels.2 |
Psychiatric Side Effects
Some psychiatrists have reported a connection between isotretinoin and psychiatric conditions such as depression, suicidal ideation, and suicide.1 However, scientists have found no conclusive proof that isotretinoin causes these conditions, so this issue remains controversial.
Dermatologists argue that acne itself causes depression, pointing out that isotretinoin can have a positive effect on mood because it clears up acne and improves self-image.8,9
Expand to read details of studies
In the journal Clinical Dermatology, Rigopoulos et al. reported that, "A retrospective cohort study reviewed the supposed risk of depression, psychotic symptoms, attempted suicide, and suicide with isotretinoin therapy. No evidence was provided to support that use of isotretinoin was correlated with an increased risk of depression, suicidal behavior, or other psychiatric disorders. Another study found no association with suicidal behavior and treatment with isotretinoin."1
In a review published in Archives of Dermatology, Goldsmith et al. points out that "Epidemiological studies to date have not shown an association between isotretinoin and depression or suicide because acne itself may be a risk factor for depression."8
However, psychiatrists suggest a causal relationship between isotretinoin and depression. Psychiatrists argue that dermatologists are unable to identify these conditions correctly. While the evidence that isotretinoin causes adverse psychiatric orders is not definitive, dermatologists are advised to check their patients' medical histories and check their patients' mental well being at each visit.1,9
Long-term Side Effects
The long-term effects of isotretinoin therapy are not well studied. In fact, we have only one study which looks at long-term side effects.
Expand to read details of study
This study published in the British Journal of Dermatology assessed long-term side effects in 720 patients treated with isotretinoin. The follow-up period of this study ranged from 2 to 12 years. The study found that 52 patients (7.2%) reported persistent side effects during the follow-up period, predominantly joint aches and dry skin. Goulden et al. reported no correlation between side effects and age, sex, cumulative dose, or number of treatments.10
Anecdotal evidence suggests that many people who take isotretinoin tend to use lip balm for decades after taking isotretinoin. Isotretinoin reduces sebum production long term. What role this plays long term in the health of the skin and in skin aging remains to be studied.
What to Keep an Eye on While Taking Isotretinoin
Doctors should check patients for changes blood parameters, such as blood cell and triglyceride counts, as well as changes in mood and vision while taking isotretinoin.3,8 Some researchers argue that monthly monitoring of blood parameters is not necessary, suggesting that doctors may check blood parameters every two months to reduce costs.9
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Some skin, mucous membrane, and eye side effects are manageable with complementary therapies such as skin lotions, sunscreen, petroleum jelly, and similar products. Some eye problems can be decreased by avoiding contact lenses and by eye washing. Visions problems, with the most notable being a rapid decrease in night vision, may require discontinuing isotretinoin therapy.2
Drug Interactions
Isotretinoin can interact with some drugs, and patients taking phenytoin, tetracyclines, vitamin A, low-estrogen oral contraceptives, and oral corticosteroids should not take isotretinoin.1
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Who Should Not Take Isotretinoin
Women cannot take isotretinoin during pregnancy because it greatly increases the risk of birth defects.1 Isotretinoin is the most teratogenic (causes birth defects) medication on the market. Birth defects include malformations of the brain, skull, face, and heart, as well as miscarriage and death.3 Therefore, the FDA and EU have created programs to prevent pregnancy in patients taking isotretinoin. These programs require using two effective birth control methods from one month before isotretinoin treatment to five weeks after treatment, preferably including oral contraceptives.2,8,11 These programs also test for pregnancy before, during, and after treatment.1 In the United States, iPLEDGE is the pregnancy risk management program for isotretinoin administration. Prescribers and patients can access the iPLEDGE registry atwww.ipledgeprogram.com.1
Additionally, patients with liver problems, kidney problems, diabetes, high blood lipids, or alcoholism should not take isotretinoin.1
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References:
- Rigopoulos D, Larios G, and Katsambas AD. "The role of isotretinoin in acne therapy: why not as first-line therapy? facts and controversies." Clinical Dermatology. 2010; 28(1): 24-30.
- McLane J. "Analysis of common side effects of isotretinoin." Journal of the American Academy of Dermatology. 2001; 45(5): 188-194.
- Tripathi S V, et al. "Side effects of common acne treatments." Expert Opinion on Drug Safety. 2013; 12: 39-51.
- Neudorfer M, et al. "Ocular Adverse Effects of Systemic Treatment With Isotretinoin." Archives of Dermatology. 2012; 148(7): 803-808.
- Karadag AS, et al. "The Effect of Different Doses of Isotretinoin on Pituitary Hormones." Dermatology. 2015; 230(4): 354-359. 5
- Lee YH, et al. "Laboratory Monitoring During Isotretinoin Therapy for Acne." JAMA Dermatology. 2015; 17033: 1.
- Ataseven A, and Ugur Bilgin A. "Effects of isotretinoin on the platelet counts and the mean platelet volume in patients with acne vulgaris." Scientific World Journal. 2014; 2014: 156464.
- Goldsmith LA, et al. "American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations." Journal of the American Academy of Dermatology. 2004; 50(6): 900-6.
- Ludot M, Mouchabac S, and Ferreri F. "Inter-relationships between isotretinoin treatment and psychiatric disorders: depression, bipolar disorder, anxiety, psychosis and suicide risks." World Journal of psychiatry. 2015; 5(2): 222-227.
- Goulden V, Layton AM, and Cunliffe WJ. "Long-term safety of isotretinoin as a treatment for acne vulgaris." British Journal of Dermatology. 1994; 131(3): 360-3.
- Zouboulis CC, and Bettoli V. "Management of severe acne." British Journal of Dermatology. 2015; 172: 27-36.
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