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Research · Medication

Isotretinoin

Isotretinoin cut acne lesions more than placebo or antibiotics in trials and topped a network analysis of acne drugs. Dry lips and skin were very common, triglycerides rose in about a quarter, and liver enzymes in about 15%. It causes severe birth defects and is sold only through iPLEDGE. Depression and suicide findings differ between studies.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US, FDA-approved for severe recalcitrant nodular acne in non-pregnant patients aged 12 and older whose acne did not respond to conventional treatment, including antibiotics. It carries a boxed warning for birth defects and is dispensed only through the iPLEDGE REMS program.
Also called
isotretinoin, oral isotretinoin, Accutane, Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, Zenatane, 13-cis-retinoic acid, Roaccutane
Taken for
severe acne, cystic acne, nodular acne, acne that came back after antibiotics, moderate acne at low dose, oily skin, rosacea, skin aging

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

Reported risks12

What people take it for, and what was found

Shown to help2

Strong

Severe and moderate acne

Shown to reduce acne lesions more than placebo or oral antibiotics, ranking first of 37 interventions in a network analysis of 221 trials.

Compared with placebo or oral antibiotics [1]; other acne treatments in a network analysis of 37 interventions [2]

The numbers and sources
Effect
Across 11 trials, isotretinoin always reduced lesion counts more than its control, which was placebo in 2, oral antibiotics in 7 and another treatment in 2 [1]. A network meta-analysis ranked oral isotretinoin first for percentage reduction in total lesions, with a mean difference of 48.41, ahead of triple combinations of a topical retinoid, benzoyl peroxide and an antibiotic [2]. In the Absorica label trial, 70% reached a 90% reduction in nodules after 20 weeks [3].
Population
760 people with mostly moderate to severe acne, mostly men, mean age 18 to 47.9 [1]; 65,601 patients in 221 trials [2]; 925 people aged 12 to 54 with severe nodular acne [3].
Sources
[1], [2], [3]
Caveats
In the trials with low risk of bias, 2 of 3 showed a significant difference from control [1]. The label trial compared two isotretinoin products, with no placebo arm [3].
Moderate

Rosacea

Shown to reduce rosacea lesions and redness at low doses, more than topical retinoids or antimicrobials, in an off-label use with 35% relapse within 6 months of stopping.

Compared with before treatment, and topical retinoids or topical antimicrobials [6]

The numbers and sources
Effect
Isotretinoin at 0.5 mg/kg/day or less reduced lesion count and redness with a large effect (SMD above 0.8). Against topical retinoids and antimicrobials, it reduced lesions more (SMD above 0.5). Lesion count and redness stayed 70% and 47% lower 16 weeks after stopping. Relapse was 35% at 5.5 months, and 0.4% had serious adverse events [6].
Population
1,445 patients in 16 randomized and non-randomized studies [6].
Sources
[6]
Caveats
Study designs varied, which limited comparisons [6]. Rosacea is not an FDA-approved use.

Mixed results2

Moderate

Against oral antibiotics plus topical treatment

Mixed results: in three trials, isotretinoin did not reduce inflammatory lesions more than antibiotics plus topical treatment, while physician-rated severity improved slightly.

Compared with oral antibiotics plus topical agents [4]

The numbers and sources
Effect
Against oral antibiotics plus topical agents, isotretinoin made no difference to investigator-counted inflammatory lesions (RR 1.01, 95% CI 0.96 to 1.06). It may slightly improve physician-rated severity (RR 1.15, 95% CI 1.00 to 1.32), with 67% more minor adverse effects (RR 1.67, 95% CI 1.42 to 1.98), such as dry lips and skin, cheilitis, vomiting and nausea [4].
Population
400 people with moderate or severe acne in 3 trials, and 351 in 2 trials, treated 20 to 24 weeks, within a Cochrane review of 31 trials and 3,836 participants aged 12 to 55 [4].
Sources
[4]
Caveats
Very low to low quality evidence. All but 3 of the 31 trials had high risk of bias in at least one area, and 12 were funded by drug companies [4].
Moderate

Lower daily doses

Mixed results: lower daily doses cleared many lesions, but conventional doses gave more responders in one trial and longer remission in a meta-analysis of adults.

Compared with conventional doses and pulsed or intermittent regimens [4][5]

The numbers and sources
Effect
In severe acne, a 95% drop in inflammatory lesions was reached by 58% on 0.1 mg/kg/day, 80% on 0.5 and 90% on 1 mg/kg/day over 20 weeks. Another trial found lesion counts fell 79%, 80% and 84% on 0.05, 0.1 and 0.2 mg/kg/day. Continuous low or conventional doses reduced inflammatory lesions more than one week a month [4]. In adults with mild to moderate acne, conventional doses gave more response and longer remission than low daily doses, and low daily doses beat pulsed doses [5].
Population
150 and 154 people with severe acne in single trials, and 40 with moderate acne [4]; adults with mild to moderate acne in pooled studies [5].
Sources
[4], [5]
Caveats
Heterogeneity prevented pooling in [4], and [5] rated the evidence low quality. Low-dose use for mild to moderate acne is off-label [5].

Not shown to help1

Limited

Skin aging

Small trials found low-dose isotretinoin did not improve sun-aged skin more than sunscreen and moisturizer alone, and did no better than tretinoin cream.

Compared with sunscreen and moisturizer alone [7]; tretinoin 0.05% cream [8]

The numbers and sources
Effect
In women aged 40 to 55, isotretinoin 20 mg three times a week for 3 months gave no clinical or microscopic difference from sunscreen and moisturizer alone, apart from a small fall in the skin marker p53 [7]. In adults aged 50 to 75 with advanced photoaging, isotretinoin 20 mg every other day for 6 months did not differ from tretinoin 0.05% cream on appearance, histology or collagen [8].
Population
32 women [7]; 24 adults, 22 completing [8].
Sources
[7], [8]
Caveats
Very small trials from one research group.

Doses studied

The Absorica label gives 0.5 to 1 mg/kg a day in two divided doses for 15 to 20 weeks (0.4 to 0.8 mg/kg for Absorica LD), with up to 2 mg/kg a day for very severe or trunk acne in adults. Its trial gave 0.5 mg/kg a day for 4 weeks, then 1 mg/kg a day for 16 weeks [3]. Dose trials in the Cochrane review used 0.05 to 1 mg/kg a day, and continuous low doses of 0.25 to 0.4 mg/kg a day [4]. The laboratory meta-analysis included trials of 40 mg a day or more for at least 4 weeks [9]. Rosacea studies used 0.5 mg/kg a day or less [6]. The skin aging trials used 20 mg three times a week [7] or every other day [8].

Risks

Reported risks11

ModerateVery common

Raised triglycerides and cholesterol

Shown to raise triglycerides markedly in 25% of people in trials, lower HDL in 15% and raise cholesterol in 7%. The changes reversed after stopping.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In clinical trials, marked rises in serum triglycerides occurred in 25%, falls in HDL in 15% and rises in cholesterol in 7%, reversing after the drug was stopped. Triglycerides above 800 mg/dL have been reported, and the rise is dose related [3]. A meta-analysis found statistically significant changes in mean lipid values during treatment, with means of 119.98 mg/dL for triglycerides and 184.74 mg/dL for total cholesterol, and found the mean changes did not reach its high-risk thresholds and few people had abnormal results [9].
Population
Isotretinoin capsule trials [3]; 1,574 patients aged 9 to 35 in 26 studies [9].
Sources
[3], [9]
Caveats
The meta-analysis abstract gives values during treatment, not the size of the change from baseline [9]. The label states the heart consequences are unknown [3].
ModerateVery common

Raised liver enzymes

Shown to raise liver enzymes mildly to moderately in about 15% of people in trials. The label also reports clinical hepatitis.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Mild to moderate rises in liver enzymes were seen in about 15% of people in clinical trials, some returning to normal with a lower dose or continued treatment. ALT, AST, GGT and alkaline phosphatase are among the tests the label lists as increased [3]. A meta-analysis found statistically significant changes in hepatic panel means, with ALT averaging 21.77 U/L and AST 22.67 U/L during treatment, and few results outside the normal range [9]. Elevated liver enzymes led to withdrawal from trials in some [1].
Population
Isotretinoin capsule trials [3]; 1,574 patients in 26 studies [9]; 760 people in 11 trials [1].
Sources
[3], [9], [1]
Caveats
The meta-analysis authors concluded that monthly laboratory testing is not supported for standard doses in the standard patient [9].
ModerateVery common

Joint, back and muscle symptoms

Shown in trials to cause joint or muscle symptoms in about 16%, with back pain in 29% of teenagers and marked creatine kinase rises in 24%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
About 16% in a clinical trial had musculoskeletal symptoms, including joint pain. In a trial of teenagers, 29% had back pain, severe in 14% of those cases, and 22% had joint pain. Marked creatine kinase rises (350 U/L or more) occurred in about 24% of 924 trial participants, some linked to vigorous exercise, and rare rhabdomyolysis has been reported [3].
Population
358 patients aged 12 and older in a pediatric trial, and 924 participants in another trial [3].
Sources
[3]
Caveats
Uncontrolled label figures with no placebo rate.
LimitedStudied in childrenCommon

Bone density and growth in teenagers

One trial found bone density declines in 9% of teenagers during a 20-week course, with no recovery 2 to 3 months later. Bone age changed in 3%.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In a trial of patients aged 12 and older, 27 of 306 (9%) had declines in bone mineral density of 4% or more at the lumbar spine or total hip, or 5% or more at the femoral neck, during 20 weeks. Repeat scans 2 to 3 months later showed no recovery. Bone age changed in 9 of 289 (3%). The label reports cases of premature growth plate closure, fractures and hyperostosis [3].
Population
306 patients aged 12 and older with bone scans, and 289 with hand x-rays [3].
Sources
[3]
Caveats
No untreated comparison group, and long-term follow-up was in 7 patients [3].
LimitedStudied in pregnancyHow often is not known

FDA boxed warning: birth defects

FDA states isotretinoin can cause life-threatening birth defects, with an extremely high risk from any amount taken during pregnancy, even briefly. The label gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states there is an extremely high risk that life-threatening birth defects will result if pregnancy occurs while taking any amount, even for short periods, and that potentially any exposed fetus can be affected. The documented defects include malformations of the skull, face, ears, eyes, brain, heart, thymus and parathyroid glands, some fatal, along with IQ scores under 85, miscarriage and premature birth [3].
Population
Human pregnancies exposed to isotretinoin, summarized in labeling [3].
Sources
[3]
Caveats
The label gives no rate. None of the 31 Cochrane trials reported birth defects, because pregnant people were excluded [4].
LimitedHow often is not known

iPLEDGE REMS

The label states isotretinoin is available only through the iPLEDGE program, with pregnancy tests before each prescription for people who can become pregnant and no blood donation.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Prescribers, pharmacies, wholesalers and patients must enroll. People who can become pregnant must have a negative pregnancy test documented before each prescription, follow pregnancy prevention requirements, show they understand the risks, and fill the prescription within 7 days of the test. Pharmacies dispense at most 30 days with no refills. Every patient must not share the drug and must not donate blood during treatment and for 1 month after [3].
Population
Labeling statement [3].
Sources
[3]
Caveats
A regulatory program, not a measured harm. A 2025 study of the program's effect on pregnancy rates was a research letter with no readable abstract and is left out.
StrongHow often is not known

Dry lips, dry skin and other skin effects

Shown to double adverse events against control, more than half of them skin dryness. Dry lips, dry skin and dry eyes are among the most frequent effects on the label.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Adverse events were twice as frequent on isotretinoin (751 events) as on control (388), and more than half were skin effects related to dryness. Stevens-Johnson syndrome, cheilitis, dry skin, acne flare and photophobia led to withdrawal in some [1]. Against antibiotics plus topical agents, minor adverse effects were 67% more frequent (RR 1.67) [4]. The label lists dry lips, dry skin, dry eye, nosebleeds, chapped lips, dermatitis and cheilitis among reactions occurring in 5% or more, and states cheilitis is dose related [3].
Population
760 people in 11 trials [1]; 351 people in 2 trials [4]; label trials [3].
Sources
[1], [4], [3]
Caveats
The sources give event counts and a floor of 5%, not the share of people affected, so the band above is the lowest the label supports.
LimitedHow often is not known

Pancreatitis

Case reports: a review found 25 published cases of pancreatitis on isotretinoin, 4 likely due to high triglycerides. No rate could be given.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Among 125 papers, 11 described 25 cases of isotretinoin-associated pancreatitis, 4 likely due to high triglycerides. The authors called triglyceride-related pancreatitis exceedingly rare and found idiosyncratic pancreatitis the more frequent type [14]. The label reports rare fatal hemorrhagic pancreatitis, with normal or raised triglycerides [3].
Population
Published case reports [14]; postmarketing reports [3].
Sources
[14], [3]
Caveats
The review states its data cannot give a frequency [14].
LimitedHow often is not known

Eye and hearing effects

The label warns of reduced night vision that can persist, dry eyes, corneal opacities and hearing loss. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Decreased night vision has been reported, sometimes sudden and in some cases persisting after stopping. Corneal opacities resolved or were resolving 6 to 7 weeks after stopping. Dry eyes can make contact lenses hard to wear. Impaired hearing has been reported, sometimes persisting after treatment [3].
Population
Trial participants and postmarketing reports [3].
Sources
[3]
Caveats
No rates or comparison groups are given.
LimitedHow often is not known

Serious skin reactions

Case reports: the label describes Stevens-Johnson syndrome and toxic epidermal necrolysis after approval, some fatal. One case led to withdrawal in trials.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label reports postmarketing erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, some resulting in death or disability, and allergic vasculitis [3]. Stevens-Johnson syndrome was the one serious adverse effect in the antibiotic comparison trials [4].
Population
Postmarketing reports [3]; trial participants [4].
Sources
[3], [4]
Caveats
Reports have no denominator.
LimitedHow often is not known

Tetracycline antibiotics and vitamin A supplements

The label warns against taking tetracyclines with isotretinoin, because raised pressure in the skull occurred in cases, some on both. It also warns against vitamin A supplements.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Isotretinoin has been linked to cases of intracranial hypertension, some involving tetracyclines, with headache, nausea, vomiting, vision changes and swelling of the optic disc. The label advises avoiding tetracyclines and vitamin A supplements, since isotretinoin is closely related to vitamin A [3]. It found no clinically significant change in a norethindrone and ethinyl estradiol pill's levels [3].
Population
Case reports and labeling statements [3].
Sources
[3]
Caveats
No rate is given.

Mixed results1

StrongCommon

Depression and suicide

Mixed results: two meta-analyses found no rise in depression or suicide, while a Swedish cohort linked treatment to more suicide attempts during and 6 months after. The label warns.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Across 25 studies, the 1-year absolute risk of depression was 3.83% and of each suicide outcome under 0.5%. Users were less likely than nonusers to attempt suicide at 2 to 4 years (RR 0.86 at 3 years), and psychiatric disorders overall did not rise (RR 1.08, 95% CI 0.99 to 1.19) [10]. In 31 studies, depression scores fell from baseline and depression prevalence fell (RR 0.588) [11]. In Sweden, suicide attempts during and up to 6 months after treatment were 1.78 times the expected number (95% CI 1.04 to 2.85), but were already raised the year before, about one extra first attempt per 2,300 treatment courses [12]. In 30,866 users, new psychiatric diagnoses were less common than on oral antibiotics (OR 0.80) and similar to topical treatment [13]. The label warns of depression, psychosis and, rarely, suicidal thoughts, attempts and suicide [3].
Population
1,625,891 participants in 25 studies [10]; 31 controlled or prospective studies [11]; 5,756 Swedish patients aged 15 to 49 [12]; 30,866 isotretinoin users with acne aged 12 to 27 and matched comparison groups, in electronic records [13].
Sources
[10], [11], [12], [13], [3]
Caveats
Observational studies. The meta-analysis of depression scores included no randomized trials [11]. Severe acne itself carries mental health burden, which the cohorts try to separate from the drug [12][13]. The band above is the 1-year depression risk [10].

Checked, no increase found1

Strong

Inflammatory bowel disease

Not linked to inflammatory bowel disease in three meta-analyses of observational studies, though the label still lists it as a warning.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across 8 studies of 2,522,422 people, isotretinoin was not associated with inflammatory bowel disease (OR 1.01, 95% CI 0.80 to 1.27), Crohn disease (OR 0.87) or ulcerative colitis (OR 1.27, 95% CI 0.94 to 1.73) [15]. A second meta-analysis of 6 studies found OR 1.08 (95% CI 0.82 to 1.42) [16], and a third pooled RR 0.94 (95% CI 0.65 to 1.36) across 5 studies [17]. The label states isotretinoin has been associated with the disease in people without prior bowel problems [3].
Population
4 case-control and 4 cohort studies [15]; 6 studies [16]; 2,159 cases and 43,180 controls, plus 5 studies pooled [17].
Sources
[15], [16], [17], [3]
Caveats
All observational, and the three reviews share studies.

Claims tested and not found

  1. That isotretinoin causes inflammatory bowel disease. Three meta-analyses of observational studies found no association, with odds ratios of 1.01, 1.08 and a risk ratio of 0.94 [15][16][17].
  2. That isotretinoin raises long-term suicide risk at the population level. Users were less likely than nonusers to attempt suicide 2 to 4 years after treatment, and psychiatric disorders overall did not rise [10].
  3. That oral isotretinoin rejuvenates aging skin. In two small randomized trials it did not beat sunscreen and moisturizer alone, nor tretinoin cream [7][8].

Sources

  1. Vallerand IA, Lewinson RT, Farris MS, et al. Efficacy and adverse events of oral isotretinoin for acne: a systematic review. British Journal of Dermatology. 2018. https://doi.org/10.1111/bjd.15668
  2. Huang CY, Chang IJ, Bolick N, et al. Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials. Annals of Family Medicine. 2023. https://doi.org/10.1370/afm.2995
  3. U.S. Food and Drug Administration. ABSORICA and ABSORICA LD (isotretinoin) capsules, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ef0cff8-19c1-4441-b780-fca6c7ee1615
  4. Costa CS, Bagatin E, Martimbianco ALC, et al. Oral isotretinoin for acne. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD009435.pub2
  5. Al Muqarrab F, Almohssen A. Low-dose oral isotretinoin for the treatment of adult patients with mild-to-moderate acne vulgaris: Systematic review and meta-analysis. Dermatologic Therapy. 2022. https://doi.org/10.1111/dth.15311
  6. King A, Tan MG, Kirshen C, et al. Low-dose isotretinoin for the management of rosacea: A systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology. 2025. https://doi.org/10.1111/jdv.20315
  7. Bagatin E, Parada MOB, Miot HA, et al. A randomized and controlled trial about the use of oral isotretinoin for photoaging. International Journal of Dermatology. 2010. https://doi.org/10.1111/j.1365-4632.2009.04310.x
  8. Bagatin E, Guadanhim LRS, Enokihara MMSS, et al. Low-dose oral isotretinoin versus topical retinoic acid for photoaging: a randomized, comparative study. International Journal of Dermatology. 2014. https://doi.org/10.1111/ijd.12191
  9. Lee YH, Scharnitz TP, Muscat J, et al. Laboratory Monitoring During Isotretinoin Therapy for Acne: A Systematic Review and Meta-analysis. JAMA Dermatology. 2016. https://doi.org/10.1001/jamadermatol.2015.3091
  10. Tan NKW, Tang A, MacAlevey NCYL, et al. Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis. JAMA Dermatology. 2024. https://doi.org/10.1001/jamadermatol.2023.4579
  11. Huang YC, Cheng YC. Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis. Journal of the American Academy of Dermatology. 2017. https://doi.org/10.1016/j.jaad.2016.12.028
  12. Sundström A, Alfredsson L, Sjölin-Forsberg G, et al. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ. 2010. https://doi.org/10.1136/bmj.c5812
  13. Paljarvi T, McPherson T, Luciano S, et al. Isotretinoin and adverse neuropsychiatric outcomes: retrospective cohort study using routine data. British Journal of Dermatology. 2022. https://doi.org/10.1111/bjd.21049
  14. Opel D, Kramer ON, Chevalier M, et al. Not every patient needs a triglyceride check, but all can get pancreatitis: a systematic review and clinical characterization of isotretinoin-associated pancreatitis. British Journal of Dermatology. 2017. https://doi.org/10.1111/bjd.15207
  15. Yu CL, Chou PY, Liang CS, et al. Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis. American Journal of Clinical Dermatology. 2023. https://doi.org/10.1007/s40257-023-00765-9
  16. Lee SY, Jamal MM, Nguyen ET, et al. Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. European Journal of Gastroenterology & Hepatology. 2016. https://doi.org/10.1097/MEG.0000000000000496
  17. Etminan M, Bird ST, Delaney JA, et al. Isotretinoin and Risk for Inflammatory Bowel Disease: A Nested Case-Control Study and Meta-analysis of Published and Unpublished Data. JAMA Dermatology. 2013. https://doi.org/10.1001/jamadermatol.2013.1344

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