This page shows what was measured, who it was measured in, and what that does not settle.
What Isotretinoin does in the body
Used for severe acne under strict pregnancy-prevention controls.
Isotretinoin converts inside cells into a form of vitamin A that binds receptors sitting directly on DNA, switching whole programmes of genes on and off. In skin this shrinks the oil glands, changes how skin cells mature and starves the bacteria that drive acne, which is why the improvement lasts after the course ends. In an embryo the same receptors direct how the face, heart, thymus and brain are built, so exposure during early pregnancy disrupts that construction in a specific and recognisable pattern.
What happened in people
In 154 exposed pregnancies, 21 babies had a distinctive pattern of major birth defects.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Average studies found no rise in depression, but cannot rule out rare severe reactions in individuals.
Where it acts
Sebaceous glands of the skin; the teratogenic site is the cephalic neural crest of the developing embryo
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · EH28UP18IF · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 108 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Formulation
A formulation is the exact made-up form a substance comes in.
A picture of it, and where the picture fails
It is like the difference between a whole bean and instant coffee.
Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.
What people get wrong. Two products with the same name are assumed to behave the same. They often do not.
The specific composition and physical form of a product, including salt, excipients and release profile.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Pregnancy outcome and malformation pattern following fetal isotretinoin exposure
✓ The study showed what it set out to show
Who was studied
Retinoic acid embryopathy investigation (Lammer et al.)
How many people
154
Study design
Multicentre case series with a prospectively observed subset
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Relative risk 25.6 (95% CI 11.4 to 57.5) for selected major malformations; 21 malformed infants, 95 elective abortions, 12 spontaneous abortions, 26 unaffected infants
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. 95 of 154 pregnancies ended in elective abortion, so the observed malformation frequency in continued pregnancies cannot be read as a population risk. The prospective subset of 36 gives the less biased estimate: 5 malformed infants, 23 normal, 8 spontaneous abortions.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, weight-based dosing over a 16 to 24 week course
Interval reported. 95% CI 11
Written into the record, not signed off as a reviewed claim.
Change in depression scores and prevalence of depression during and after isotretinoin treatment for acne
✗ The study did not show it
Who was studied
Systematic review and meta-analysis of isotretinoin and depression (Huang and Cheng)
How many people
31
Study design
Systematic review and meta-analysis of controlled and prospective studies
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Controlled studies: standardised mean difference -0.334 (95% CI -0.680 to 0.011), not significant; prevalence of depression after treatment relative risk 0.588 (0.382 to 0.904); mean depression scores fell, SMD -0.335 (-0.498 to -0.172)
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No randomised controlled trials were available for inclusion and inter-study variation was large. A pooled average cannot detect a rare idiosyncratic reaction.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule, weight-based dosing over a 16 to 24 week course
Interval reported. 95% CI -0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Where a source records it acting
Skin: Inhibits sebaceous gland function and keratinization; the label records that the exact mechanism of action is unknown
US prescribing information · 0114567b-3bac-490d-b9eb-03a6c5d90935 · read 2026-08-28
Start
Isotretinoin
What a person takes: Oral capsule, weight-based dosing over a 16 to 24 week course.
The measurement behind this step
Oral isotretinoin dosed by body weight to a cumulative target over four to six months. Conventional formulations require a fatty meal for adequate absorption; lidose formulations do not. Dispensing is gated by the iPLEDGE system, which requires registration of prescriber, patient, pharmacy and wholesaler and entry of pregnancy test results within a defined window.
Getting in
Oral capsules over a course of several months
Taken by mouth daily for four to six months, with the total dose calculated by body weight, and the prescription released only when the programme requirements are met.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Oral isotretinoin dosed by body weight to a cumulative target, typically over 16 to 24 weeks. Conventional formulations require a fatty meal for absorption; lidose formulations do not, and the difference materially changes exposure.
Enters cells and isomerises to the active retinoid
Inside cells it converts into the naturally occurring form of vitamin A acid, which is what actually does the work.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Highly lipophilic and extensively protein-bound. Intracellular isomerisation to all-trans-retinoic acid and oxidation to 4-oxo metabolites generate the species with meaningful retinoic acid receptor affinity; isotretinoin itself binds the receptors weakly.
The active form docks onto receptors that sit directly on DNA and act as switches for large sets of genes.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Binds RAR-alpha, beta and gamma, which heterodimerise with retinoid X receptors and occupy retinoic acid response elements in target gene promoters, releasing corepressors and recruiting coactivators.
Sebaceous glands involute — and neural crest patterning is disrupted
In skin, oil glands shrink and the follicle stops blocking. In an embryo, the same switches misdirect how the face, heart and thymus are built.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
In sebocytes, transcriptional reprogramming causes gland involution, reduced sebum, normalised follicular keratinisation and loss of the anaerobic niche for Cutibacterium acnes. In the embryo, the same receptors govern cephalic neural-crest migration and patterning, and disruption produces defects in craniofacial, conotruncal cardiac, thymic and central nervous system structures.
Durable acne remission; a 25.6-fold malformation risk if pregnancy occurs
Severe acne clears and often stays clear after the course ends. Exposure during pregnancy carries a twenty-five-fold risk of major malformations, which is why the programme exists.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Measured: durable remission of severe recalcitrant nodular acne, the reason no alternative displaced it in four decades. Measured: relative risk 25.6 (95% CI 11.4 to 57.5) for selected major malformations after fetal exposure, with 21 malformed infants among 154 exposed pregnancies.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Patients with severe recalcitrant nodular acne, registered in iPLEDGE, with those who can become pregnant subject to mandatory contraception and repeated pregnancy testing.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of Amnesteem in pediatric patients less than 12 years of age have not been established.”
US prescribing information · b2cb63c9-f825-4991-9a2c-6260f1bbcc2c · read 2026-08-30
On older people, the label states: “Clinical studies of Amnesteem did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.”
US prescribing information · b2cb63c9-f825-4991-9a2c-6260f1bbcc2c · read 2026-08-30
On people who are pregnant, the label states: “Pregnancy Exposure Registry There is a pregnancy exposure registry that documents pregnancies in patients exposed to isotretinoin during pregnancy.”
US prescribing information · b2cb63c9-f825-4991-9a2c-6260f1bbcc2c · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of isotretinoin in either animal or human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · b2cb63c9-f825-4991-9a2c-6260f1bbcc2c · read 2026-08-30
Where the result stopped carrying
Approved 1982, embryopathy characterised 1985, and three successive prevention systems were required between 1988 and 2006
Each system was replaced because exposed pregnancies continued to occur under it
The teratogenicity is the on-target pharmacology in a different tissue, so no structural modification of the molecule can remove it
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
A different form was studied
The studied form is not the form on the shelf.
On this record: This record is linked to 1 related forms. Evidence does not carry across all of them.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule, weight-based dosing over a 16 to 24 week course
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S3, S5, S6.
No source is stored against this line.
What is in the pack
Oral isotretinoin dosed by body weight to a cumulative target over four to six months. Conventional formulations require a fatty meal for adequate absorption; lidose formulations do not. Dispensing is gated by the iPLEDGE system, which requires registration of prescriber, patient, pharmacy and wholesaler and entry of pregnancy test results within a defined window.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Teratogenicity dominates: relative risk 25.6 (95% CI 11.4 to 57.5) for selected major malformations after fetal exposure, in a characteristic craniofacial, conotruncal cardiac, thymic and central nervous system pattern. Two forms of contraception and repeated pregnancy testing are mandated for patients who can become pregnant, continuing for a defined period after the last dose. Other effects are cheilitis and xerosis in nearly all patients, hypertriglyceridaemia, transaminase elevation, night vision impairment, myalgia, and idiopathic intracranial hypertension particularly with concomitant tetracyclines. The depression association has not been supported at population level by meta-analysis, which is a statement about averages rather than about individuals.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule, weight-based dosing over a 16 to 24 week course
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Conventional formulations require a fatty meal for adequate absorption; lidose formulations do not. Dispensing is gated by the iPLEDGE system, which requires registration of prescriber, patient, pharmacy and wholesaler and entry of pregnancy test results within a defined window.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
109 products list this as an active ingredient in the United States drug directory. 109 of them contain it and nothing else.
FDA National Drug Code directory · 0591-2501 · read 2026-08-29
They are sold as capsule, capsule, gelatin coated, capsule, liquid filled and powder, taken oral.
FDA National Drug Code directory · 0591-2501 · read 2026-08-29
The regulator's established pharmacologic class for it is retinoid [epc] and retinoids [cs].
FDA National Drug Code directory · 0591-2501 · read 2026-08-29
21 published labels name it as an active ingredient. 21 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · b2cb63c9-f825-4991-9a2c-6260f1bbcc2c · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · b2cb63c9-f825-4991-9a2c-6260f1bbcc2c · read 2026-08-29
12 marketed supplement labels list this ingredient, classed as non-nutrient/non-botanical, other combinations and vitamin.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Isotretinoin is soft gelatin capsules at Soft gelatin capsules: 10 mg, 20 mg, 30 mg and 40 mg, recorded as prescription product; fda label in effect 2024-06-26 in the United States.
US prescribing information · 0114567b-3bac-490d-b9eb-03a6c5d90935 · read 2026-08-28
Recorded price in US: 1.86128–11.936 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 79 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
Evidence on this page does not automatically apply to this one.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Isotretinoin studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That a null pooled depression effect excludes idiosyncratic psychiatric reactions in individuals; no randomised trials were available and variation was large
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a computerised prevention programme eliminates exposed pregnancies; deliberate circumvention of pregnancy testing has itself been measured
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the malformation frequency among continued pregnancies in the 1985 series is a population risk estimate; 95 of 154 pregnancies were electively terminated
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Isotretinoin are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Relative risk 25.6 for a characteristic pattern of major malformations
In plain words
In the study that defined the syndrome, 21 of 154 exposed pregnancies produced infants with major malformations in a distinctive pattern affecting the face, heart, thymus and brain.
What was measured
Relative risk for selected major malformations after fetal isotretinoin exposure, with the malformation pattern by organ system
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
An investigation of 154 human pregnancies with fetal isotretinoin exposure recorded 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions and 21 malformed infants. A prospectively observed subset of 36 pregnancies produced 8 spontaneous abortions, 23 normal infants and 5 malformed infants. Exposure carried a relative risk of 25.6 (95% CI 11.4 to 57.5) for a group of selected major malformations. Among the 21 malformed infants the pattern involved microtia or anotia (15), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4) and central nervous system malformations (18) — closely resembling animal retinoid teratogenesis, and consistent with a deleterious effect on cephalic neural-crest cell activity.
Written into the record, not signed off as a reviewed claim
Three prevention systems in twenty-four years, each because the last leaked
In plain words
A voluntary programme was replaced by a stricter one, and that by a mandatory computerised registry. Each escalation happened because pregnancies kept occurring.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Isotretinoin was approved in 1982 and the embryopathy was characterised in 1985. A Pregnancy Prevention Program followed in the late 1980s, relying on physician and patient education and voluntary compliance. The System to Manage Accutane-Related Teratogenicity replaced it in 2001 with qualification stickers and registration. iPLEDGE replaced that in 2006 as a mandatory computerised system in which prescribers, patients, pharmacies and wholesalers must all be registered, pregnancy tests must be entered before a prescription can be dispensed, and a dispensing window closes automatically. Each replacement was prompted by continuing exposed pregnancies under the previous one. The escalation is itself the evidence: an entirely avoidable harm was not in fact being avoided by education alone.
Written into the record, not signed off as a reviewed claim
Patients circumvent the pregnancy testing, and the rate has been measured
In plain words
A study set out to quantify how often patients deliberately get around the iPLEDGE pregnancy test. The number is not zero.
What was measured
Rate of deliberate circumvention of mandatory pregnancy testing within the iPLEDGE programme
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A study published in 2022 measured the rate at which patients deliberately circumvent iPLEDGE pregnancy testing. That such a measurement exists, and was undertaken by dermatologists rather than regulators, is the substance of the point: a control system whose critical input is a test the patient can arrange to have someone else take, or arrange around, has a failure mode that no amount of computerisation closes. Related work documents the counselling burden the programme places on dermatologists and the readability problems of its comprehension assessment. A risk-management programme is a socio-technical system, and its measured failure rate is a property of the whole system rather than of the drug.
Written into the record, not signed off as a reviewed claim
The depression allegation does not survive meta-analysis
In plain words
Pooling 31 studies, depression scores fell rather than rose during isotretinoin treatment, and the prevalence of depression declined after it.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A systematic review and meta-analysis of literature through September 2016 included 31 studies meeting criteria of controlled or prospective non-controlled trials in 15 or more acne patients receiving isotretinoin. In the controlled studies, change in depression scores from baseline did not differ significantly between isotretinoin and alternative treatment (standardised mean difference -0.334, 95% CI -0.680 to 0.011). The prevalence of depression after isotretinoin treatment significantly declined (relative risk 0.588, 95% CI 0.382 to 0.904) and mean depression scores fell significantly from baseline (SMD -0.335, 95% CI -0.498 to -0.172). The authors conclude that isotretinoin does not appear to increase depression risk and that treating acne appears to ameliorate depressive symptoms. Limitations are stated: no randomised controlled trials were reviewed and inter-study variation was large.
Written into the record, not signed off as a reviewed claim
A pooled null on depression does not settle individual susceptibility
In plain words
The average patient does not get more depressed. That is compatible with a small number of people reacting badly, which a pooled average cannot detect.
What was measured
That a null pooled effect on depression scores demonstrates no individual can experience a psychiatric reaction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The meta-analysis included no randomised controlled trials and reported large inter-study variation. It measures the average change in depression scores across populations, and a rare idiosyncratic reaction in a small subgroup would not shift that average detectably. Confounding runs the other way as well: severe acne is itself associated with depression, so treating it successfully should improve mood, and a treated cohort improving on average is consistent both with no drug effect and with a harmful effect in a minority masked by benefit in the majority. The defensible statement is that no population-level increase in depression has been demonstrated. That is materially different from a demonstration that no individual is affected, and the continuing case-report and cohort literature reflects that gap.
Written into the record, not signed off as a reviewed claim
The therapeutic effect and the teratogenic effect are one mechanism
In plain words
The same receptors that shrink oil glands direct how an embryo's face, heart and brain are built. No version of the drug separates the two.
What was measured
Malformation pattern by organ system, mapped to cephalic neural-crest derivatives
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Isotretinoin acts through isomerisation to tretinoin and oxidation to 4-oxo metabolites, which bind retinoic acid receptors alpha, beta and gamma as ligand-activated transcription factors. In sebaceous glands this produces involution and durable remission. In the embryo the same receptors control cephalic neural-crest migration and patterning, and the malformation pattern observed — microtia, micrognathia, conotruncal cardiac defects, thymic defects, central nervous system malformations — maps precisely onto neural-crest-derived structures. The teratogenicity is not an off-target toxicity that a medicinal chemist could engineer away; it is the on-target pharmacology operating in a different tissue at a different time. That is why the answer has always been a control system rather than a better molecule.
Written into the record, not signed off as a reviewed claim
Restriction is a third option, and this is what it costs
In plain words
The drug was neither withdrawn nor left alone. It sits behind a national computer system that every prescriber, pharmacy and patient has to work through.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Every other entry in this file resolves to withdraw or not withdraw. Isotretinoin resolves to neither. It remains available because severe nodular acne scars permanently and nothing else produces durable remission, and because the harm is confined to one avoidable circumstance. The price is a permanent national infrastructure: registration of prescribers, patients, pharmacies and wholesalers, mandated contraception, repeated pregnancy testing with results entered before dispensing, and automatic dispensing windows. The published dermatology literature documents the counselling burden this places on clinicians, the readability problems of the comprehension assessment, and the deliberate circumvention that occurs anyway. Restriction is a real option and it is not a free one.
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What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A vitamin A derivative that clears severe acne durably and carries a relative risk of 25.6 (95% CI 11.4 to 57.5) for a characteristic pattern of major malformations after fetal exposure — retained on the market for four decades behind escalating pregnancy-prevention systems, while the separate depression allegation has not survived meta-analysis.
Recorded evidence blocks (11)
Q2
On the Isotretinoin label: indicated for what?
"Isotretinoin capsules are indicated for the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Because of significant adverse reactions associated with its use, isotretinoin capsules are reserved for…": indications and usage on Isotretinoin's label. DailyMed label · 1cf11710-f966-4529-8e08-02175f588bca · 2026-08-20
Q3
133 registered trials of Isotretinoin — at which phases?
Registered studies posting no result
102 of 133
133 registered studies of Isotretinoin: 45 phase2, 35 phase1, 24 phase3, 17 na, 15 phase4, 4 na or unstated, 3 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
364 with a PubMed record
Show the evidence
phase2
45
phase1
35
phase3
24
na
17
phase4
15
na or unstated
4
9 more recorded rows
early phase1
3
completed
85
unknown
17
terminated
9
recruiting
7
not yet recruiting
6
withdrawn
6
active not recruiting
2
enrolling by invitation
1
recorded 2026-09-01 · last checked 2026-09-04
Q4
14 of Isotretinoin's trials stopped: safety, accrual/recruitment, funding/business, other?
safety (1), accrual/recruitment (8), funding/business (3) and other (2): Isotretinoin's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"No enrollment"; 14 of 133 registered studies
Show the evidence
Trial
NCT00003405
withdrawn; "No enrollment"
NCT00003564
withdrawn; "Study withdrawn."
NCT00003599
withdrawn; "Withdrawn study."
NCT00138151
terminated; "Slow accrual and lack of study drug"
NCT00176527
terminated; "accrual goal met"
NCT00533169
terminated; "Lack of enrollment."
8 further recorded trials
NCT00555399
terminated; "No Sponsor funding for continuation of trial"
NCT00609739
terminated; "Low accrual"
NCT01103375
terminated; "Slow accrual"
NCT01319838
withdrawn; "no patient enrollment"
NCT01560585
terminated; "Adverse events in 2/3 participants; study was halted but not restarted after this due to insufficnet funds as well"
NCT02641782
terminated; "Antibody supply was discontinued by United Therapeutics Corporation."
NCT02795143
withdrawn; "PI (Responsible Party) transferred to new institution prior to enrollment and protocol was closed."
NCT04909515
withdrawn; "Study terminated due to business priorities"
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Isotretinoin used Isotretinoin 40 mg — over how long?
studies of Isotretinoin used the recorded amount. ClinicalTrials.gov · 2026-09-01
8 recorded entries; human; also "Isotretinoin 40 mg", "PAT-001, 0.1%", "PAT-001, 0.2%"
Show the evidence
human
NCT01863615
Isotretinoin 40 mg
NCT02864082
PAT-001, 0.1%
NCT02864082
PAT-001, 0.2%
NCT02864082
Vehicle for PAT-001 0.1%
NCT02864082
Vehicle for PAT-001 0.2%
NCT06242288
ISOtretinoin 20 MG
2 more recorded rows
humanNCT06447480
ISOtretinoin 5 MG
humanNCT06485505
ISOtretinoin 10 MG
recorded 2026-09-01 · last checked 2026-09-04
Q6
Isotretinoin's half-life is 18 hours — which schedules were studied?
18 hours, the half-life Isotretinoin's label states: "Elimination The mean elimination half-lives of isotretinoin and its 4-oxo-isotretinoin metabolite were: 18 hours and 38 hours, respectively, after a single oral isotretinoin 40 mg dose." DailyMed label · 1cf11710-f966-4529-8e08-02175f588bca · 2026-08-20
tmax 6.4 hours.
Show the evidence
half lifepharmacokinetics
18 hours; Elimination The mean elimination half-lives of isotretinoin and its 4-oxo-isotretinoin metabolite were: 18 hours and 38 hours, respectively, after a single oral isotretinoin 40 mg dose.
tmaxpharmacokinetics
6.4 hours; Absorption Following Isotretinoin Administration The isotretinoin mean T max was 6.4 hours under fed conditions and 2.9 hours under fasting conditions following administration of a single 40 mg dose.
metabolismpharmacokinetics
Metabolism: Isotretinoin is primarily metabolized by CYP2C8, 2C9, 3A4, and 2B6 in vitro .
recorded 2026-08-20 · last checked 2026-09-04
Q7
Which running trial of Isotretinoin could settle lifespan?
NCT06047535 measures 2-year progression free survival, reading out 2027-08-15.
3 open trials; n 62; "Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Combined With Isotretinoin for Maintenance Treatment of Patients With High-Risk Neuroblastoma in First Complete Response."
Show the evidence
Trial
NCT06047535
"Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Combined With Isotretinoin for Maintenance Treatment of Patients With High-Risk Neuroblastoma in First Complete Response."; n 62; "2-year progression free survival"; 2027-08-15
NCT06172296
"Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma"; n 478; "Event free survival (EFS)"; 2029-12-31
NCT03126916
"Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)"; n 750; "Event free survival (EFS) (Arm A, B, D, and E)"; 2030-09-30
Q8
Which 44 trials of Isotretinoin posted no result?
Posted no result
44 of 44 completed trials
Registrations
NCT00000764, NCT00002506, NCT00001073, NCT01888328, NCT01888289 and NCT00003585, and 38 more
Completion dates
oldest 1996-07; newest 2024-01-01
Show the evidence
Trial
NCT00000764
1996-07
NCT00002506
1999-02
NCT00001073
2001-03
NCT01888328
2001-06
NCT01888289
2001-09
NCT00003585
2002-08
14 further recorded trials
NCT01888341
2002-08
NCT00014729
2002-09
NCT00025012
2004-02
NCT00003619
2004-04
NCT00038376
2005-06-30
NCT00021359
2005-10
NCT00078988
2006-09
NCT00416585
2006-11
NCT00040872
2007-01
NCT00701740
2008-06
NCT00054561
2009-05-01
NCT00217412
2009-09
NCT00882531
2009-09
NCT01404130
2010-11
Q9
At the median, Isotretinoin's trials enrolled 50 people — anything larger?
Median enrolment
50
Largest enrolment
100000
Registered trials counted
126
Q10
What do 9508 spontaneous reports say about Isotretinoin — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Isotretinoin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 9508 reaction mentions were counted: depression 1821; unintended pregnancy 1530; pregnancy 1288; abortion induced 963. FAERS via Open Targets · CHEMBL547 · 2026-06-24
Show the evidence
depression
1821
unintended pregnancy
1530
pregnancy
1288
abortion induced
963
suicidal ideation
902
mood altered
760
4 more recorded rows
dry skin
751
blood triglycerides increased
686
lip dry
421
abortion spontaneous
386
recorded 2026-06-24 · last checked 2026-09-04
Q11
Which 10 reactions does Isotretinoin's label not list?
Metabolism: Isotretinoin is primarily metabolized by CYP2C8, 2C9, 3A4, and 2B6 in vitro .
pharmacokinetics
Drug Interaction Studies Phenytoin: No clinically significant differences in the pharmacokinetics of phenytoin (CYP2C9 substrate) were observed when used concomitantly with isotretinoin.
clinical_pharmacology
Metabolism: Isotretinoin is primarily metabolized by CYP2C8, 2C9, 3A4, and 2B6 in vitro .
clinical_pharmacology
Drug Interaction Studies Phenytoin: No clinically significant differences in the pharmacokinetics of phenytoin (CYP2C9 substrate) were observed when used concomitantly with isotretinoin.
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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