This page shows what was measured, who it was measured in, and what that does not settle.
What Ethosuximide does in the body
Ethosuximide is thought to suppress that current, so the cells stop bursting and the rhythm cannot form.
An absence seizure is the thalamus and the cortex falling into a rhythm together, about three beats a second. The thalamus can produce that rhythm because its cells carry a slow calcium current that lets them fire in bursts. The drug does nothing useful for a convulsion, because a convulsion is not made this way, and the label warns it can make convulsions more frequent if it is the only drug someone takes.
Why people take it. Absence seizures, the brief blank spells of childhood absence epilepsy
What happened in people
Freedom from treatment failure at 16 weeks of 53% on ethosuximide, 58% on valproic acid and 29% on lamotrigine, with video-EEG confirmation
✎ 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 recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Phase 3 double-blind randomised active-controlled trial, three parallel arms
Compared against
Not recorded for this study
Kind of result
What a body can do day to day
What was found
Ethosuximide 53% and valproic acid 58% (OR 1.26, 95% CI 0.80 to 1.98, P=0.35), both above lamotrigine at 29% (OR 2.66, 1.65 to 4.28 and 3.34, 2.06 to 5.42, P<0.001)
Repeated elsewhere
Unreplicated
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. Attentional dysfunction occurred in 49% on valproic acid against 33% on ethosuximide (OR 1.95, 95% CI 1.12 to 3.41, P=0.03). There was no untreated arm, so the absolute contribution of drug to that 33% cannot be separated from the epilepsy.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and oral solution
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
Ethosuximide (Zarontin) United States prescribing information: Clinical Pharmacology, Warnings and Precautions, retrieved from the openFDA drug label endpoin… · a recorded source, not a stored snapshot
Freedom-from-failure rate 12 months after randomisation, with video-EEG assessment
Ethosuximide 45% and valproic acid 44% (OR 0.94, 95% CI 0.58 to 1.52, P=0.82), both above lamotrigine at 21% (OR 3.08, 1.81 to 5.33 and 2.88, 1.68 to 5.02, P<0.001)
Repeated elsewhere
Unreplicated
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. Only 37% of all enrolled subjects were free from treatment failure on their first medication at 12 months. Almost two thirds of the 125 failing for lack of seizure control were on lamotrigine; 42% of the 115 discontinuing for adverse events were on valproic acid.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and oral solution
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
Ethosuximide (Zarontin) United States prescribing information: Clinical Pharmacology, Warnings and Precautions, retrieved from the openFDA drug label endpoin… · a recorded source, not a stored snapshot
What we know
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.
Start
Ethosuximide
What a person takes: Oral capsule and oral solution.
The measurement behind this step
The oral solution matters more than usual because the population is children, many under ten, who cannot reliably swallow a capsule and whose dose is weight-based. There is no injectable form and no extended-release form; the long half-life makes one unnecessary.
Getting in
Swallowed, absorbed well, and cleared slowly
The capsule or syrup is well absorbed and the drug persists long enough that levels move slowly. That is convenient, and it also means a change takes days to show its full effect.
╌╌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
Ethosuximide is a small, water-soluble succinimide with low protein binding and a long elimination half-life, cleared mainly by hepatic metabolism with a portion excreted unchanged. Enzyme-inducing anti-seizure drugs shorten its half-life, which is one reason the label warns about proceeding slowly when adding or removing other medication.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
Reaching the cell
It reaches the thalamus, where absence seizures are generated
The molecule is small and distributes freely into brain tissue. The circuit that matters is the loop between the thalamus and the cortex, which is where the three-per-second rhythm is made.
╌╌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
Low protein binding and small size give free distribution into brain and cerebrospinal fluid. The relevant compartment is the thalamocortical circuit, specifically the relay neurons and the reticular nucleus whose low-threshold burst firing sustains spike-and-wave oscillation.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
What it acts on
It is thought to suppress the slow calcium current that lets thalamic cells burst
Thalamic cells can fire in bursts because of a slow calcium current that primes them. Damping it stops the bursting, and without bursting the rhythm has nothing to run on.
╌╌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
The modern account is reduction of T-type low-voltage-activated calcium current in thalamic neurons. The United States label does not adopt it: its Clinical Pharmacology paragraph describes suppression of three cycle per second spike-and-wave activity apparently by depression of the motor cortex and elevation of the seizure threshold, and names no molecular target at all.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
The change it makes
The three-per-second rhythm cannot form
Without synchronised bursting the thalamus and cortex stop locking together, the spike-and-wave pattern disappears from the EEG, and the blank spells stop.
╌╌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
Suppression of spike-and-wave discharge is the observable and the one the label describes. Because the mechanism is specific to the thalamocortical oscillation, it confers nothing against focal or convulsive seizures, and the label warns that monotherapy in mixed epilepsy may increase grand mal frequency.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
What that does for a person
Freedom from failure in 53% at 16 weeks, and better attention than valproate
In the one class I trial in this syndrome, 53% of children were still free from treatment failure at 16 weeks against 58% on valproate and 29% on lamotrigine. Attentional problems affected 33% against 49% on valproate.
╌╌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
Efficacy is established against two active comparators in a 453-child double-blind randomised trial with video-EEG confirmation, followed to 12 months. Ethosuximide is first choice on the attentional endpoint rather than on the seizure endpoint, on which it and valproate are indistinguishable.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
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.
Children with childhood absence epilepsy, and almost nobody else. Ethosuximide does nothing for convulsive seizures and the label warns it can make them more frequent when used alone in mixed epilepsy.
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: “Safety and effectiveness in pediatric patients below the age of 3 years have not been established.”
US prescribing information · 8a5cc930-0b36-48a8-9ad0-de633b208742 · read 2026-08-30
On people who are pregnant, the label states: “Usage in Pregnancy: Ethosuximide crosses the placenta.”
US prescribing information · 8a5cc930-0b36-48a8-9ad0-de633b208742 · read 2026-08-30
Where the result stopped carrying
Lamotrigine, a drug that wins first-line trials in focal epilepsy, controlled absence seizures in only 29% at 16 weeks and 21% at 12 months, and accounted for almost two thirds of all failures for lack of seizure control
Valproate matched ethosuximide on seizures and lost on attention, which in this syndrome is the endpoint the disease itself damages
The label mechanism paragraph has never been updated to reflect fifty years of subsequent work on thalamic calcium currents
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.
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 (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. 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 and oral solution
✎ 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
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
The oral solution matters more than usual because the population is children, many under ten, who cannot reliably swallow a capsule and whose dose is weight-based. There is no injectable form and no extended-release form; the long half-life makes one unnecessary.
✎ 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
No boxed warning, and a warnings section that is almost entirely haematological and immunological rather than neurological. Blood dyscrasias including fatal cases have been reported, with periodic blood counts advised and a count recommended whenever infection symptoms appear. Drug-induced immune thrombocytopenia has occurred 1 to 3 weeks after starting, with platelet nadirs of 2,000 to 3,000, recurrence on re-challenge, and a direction never to use the drug again in an affected patient. Systemic lupus erythematosus has been reported. Abnormal liver and renal function studies occur, and periodic urinalysis and liver function testing is advised. Used alone in mixed epilepsy it may increase grand mal seizure frequency, and abrupt withdrawal may precipitate absence status. Patients are to be told before starting that a rash may herald a serious medical event. The class-wide suicidality warning applies.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Childhood Absence Epilepsy comparative monotherapy trial registration (NCT00088452) · a recorded source, not a stored snapshot
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 and oral solution
✎ 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
There is no injectable form and no extended-release form; the long half-life makes one unnecessary.
✎ 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
16 products list this as an active ingredient in the United States drug directory. 16 of them contain it and nothing else.
FDA National Drug Code directory · 68999-064 · read 2026-08-29
They are sold as capsule, capsule, liquid filled, powder and solution, taken oral.
FDA National Drug Code directory · 68999-064 · read 2026-08-29
The regulator's established pharmacologic class for it is anti-epileptic agent [epc] and decreased central nervous system disorganized electrical activity [pe].
FDA National Drug Code directory · 68999-064 · read 2026-08-29
12 published labels name it as an active ingredient. 12 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 8a5cc930-0b36-48a8-9ad0-de633b208742 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 8a5cc930-0b36-48a8-9ad0-de633b208742 · read 2026-08-29
ETHOSUXIMIDE is oral at HOW SUPPLIED Ethosuximide Oral Solution USP is an orange-red colored oral solution., recorded as fda label in effect 2025-10-17 in the United States.
US prescribing information · 8a5cc930-0b36-48a8-9ad0-de633b208742 · read 2026-08-30
Recorded price in US: 0.09388 USD per one millilitre, across 2 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
Recorded price in US: 0.2483 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 5 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.
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.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Ethosuximide 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 T-type calcium channel block is the established mechanism: the label names no target, and whether the current is suppressed enough at human plasma concentrations has been contested for decades
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 33% attentional dysfunction rate on ethosuximide is entirely a drug effect, when the trial had no untreated arm
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 childhood absence epilepsy is reliably controlled by first-line treatment, when 63% of enrolled children had failed their first drug by 12 months
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 per-unit price reflects the cost of making a 141-dalton molecule in one cyclisation step
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.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records 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 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 Ethosuximide 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.
The first class I randomised trial in any generalised epilepsy, and this drug won it
In plain words
Four hundred and fifty-three children with newly diagnosed absence epilepsy were randomly assigned, double-blind, to one of the three drugs anyone uses. Ethosuximide and valproate controlled the seizures equally well and lamotrigine did not, and ethosuximide cost less attention than valproate.
What was measured
Freedom from treatment failure at 16 weeks, with video-EEG confirmation, and attentional dysfunction as a co-measured outcome
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Glauser and colleagues randomised 453 children with newly diagnosed childhood absence epilepsy double-blind to ethosuximide, valproic acid or lamotrigine, titrating each to seizure freedom, maximum allowable dose or a treatment-failure criterion. The primary outcome was freedom from treatment failure at 16 weeks, with attentional dysfunction as the secondary outcome. Freedom-from-failure was 53% for ethosuximide and 58% for valproic acid, statistically indistinguishable (OR with valproate against ethosuximide 1.26, 95% CI 0.80 to 1.98, p=0.35), and both were higher than lamotrigine at 29% (OR ethosuximide against lamotrigine 2.66, 95% CI 1.65 to 4.28; OR valproate against lamotrigine 3.34, 2.06 to 5.42; p<0.001 for both). There were no significant differences in discontinuation for adverse events at 16 weeks. Attentional dysfunction was more common with valproic acid than ethosuximide, in 49% of children against 33% (OR 1.95, 95% CI 1.12 to 3.41, p=0.03). The 12-month report described the trial as the first randomised controlled trial meeting International League Against Epilepsy criteria for class I evidence for childhood absence epilepsy, or for any type of generalised seizure in adults or children.
Written into the record, not signed off as a reviewed claim
At twelve months, only 37% of all the children were still free from failure
In plain words
The 16-week figures look reasonable. Followed for a year, only 37% of all enrolled children were still succeeding on the first drug they were given, whichever drug that was.
What was measured
Freedom-from-failure rate at 12 months, with video-EEG assessment, and the split of failures between lack of control and intolerable adverse events
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 12-month report covered 446 evaluable children of 453 enrolled. By 12 months after starting therapy, only 37% of all enrolled subjects were free from treatment failure on their first medication. Freedom-from-failure rates were 45% for ethosuximide and 44% for valproic acid (OR 0.94, 95% CI 0.58 to 1.52, p=0.82), both higher than lamotrigine at 21% (OR ethosuximide against lamotrigine 3.08, 95% CI 1.81 to 5.33; valproate against lamotrigine 2.88, 1.68 to 5.02; p<0.001 for both). Treatment failures split by cause: almost two thirds of the 125 children failing for lack of seizure control were in the lamotrigine arm, while the largest single group of the 115 discontinuing for adverse events, 42%, was in the valproate arm. Childhood absence epilepsy has a reputation as the benign end of paediatric epilepsy, and this trial measured what that reputation is worth on first-line treatment: fewer than two children in five.
Written into the record, not signed off as a reviewed claim
The label mechanism paragraph predates the target it is now said to act on
In plain words
Every textbook says ethosuximide blocks T-type calcium channels in the thalamus. Its own label says it suppresses three-per-second spike-and-wave activity by depressing the motor cortex and raising the seizure threshold, language from 1960 that names no molecule at all.
What was measured
That the T-type calcium channel mechanism taught for this drug is an established fact about how it works in people. It is the best available explanation, it is not on the label, and its quantitative fit to human concentrations remains contested.
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The United States prescribing information for Zarontin has no Mechanism of Action section. Its Clinical Pharmacology paragraph reads, in full, that ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness common in absence seizures, and that the frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli. That is a description of an EEG observation and a pair of nineteenth-century physiological abstractions. The T-type calcium channel account arrived decades later, and the thalamic low-threshold current it depends on was characterised long after this drug was licensed. The account is well supported as an explanation of how absence seizures are generated. What has been argued for thirty years is whether ethosuximide suppresses that current sufficiently at the plasma concentrations achieved in patients to account for the clinical effect, and no regulatory document has ever adopted it.
Source
Ethosuximide United States prescribing information, Clinical Pharmacology (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Used alone in mixed epilepsy, it can make convulsions more frequent
In plain words
Ethosuximide treats one seizure type and nothing else. The label warns that in a child who also has convulsive seizures, using it on its own may increase how often those happen.
What was measured
Labelled warning of increased grand mal seizure frequency on ethosuximide monotherapy in mixed epilepsy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Precautions section states that ethosuximide, when used alone in mixed types of epilepsy, may increase the frequency of grand mal seizures in some patients. This is the mirror image of the sodium-channel blockers that worsen absence and myoclonic seizures, and it is the reason getting the epilepsy syndrome right matters more than getting the drug right. Some children with childhood absence epilepsy go on to have generalised tonic-clonic seizures as well, and that is the clinical situation in which this warning applies and the commonest reason valproate is chosen over ethosuximide despite the attentional data. No proportion is stated here because none was verified. The same section warns that abrupt withdrawal of anticonvulsant medication may precipitate absence status.
Source
Ethosuximide United States prescribing information, Precautions, General (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Fatal blood dyscrasias, lupus, and a platelet count that fell to 2,000
In plain words
The warnings on this drug are haematological and immunological rather than neurological. Blood disorders including fatal ones have been reported, drug-induced immune destruction of platelets has taken counts down to 2,000, and cases of lupus have occurred.
What was measured
Reported blood dyscrasias, drug-induced immune thrombocytopenia with specified platelet nadirs, and systemic lupus erythematosus cases
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Warnings section reports blood dyscrasias, including some with fatal outcome, and advises periodic blood counts, with a count considered whenever signs or symptoms of infection such as sore throat or fever develop. Drug-induced immune thrombocytopenia has been reported, with symptom onset 1 to 3 weeks after starting, recurrence within one day of re-challenge in one patient, and platelet nadirs of 2,000 and 3,000 per cubic millimetre where specified; the label directs discontinuation, serial platelet counts, assessment for drug-dependent antiplatelet antibodies where possible, and permanent avoidance thereafter. Cases of systemic lupus erythematosus have been reported. Ethosuximide produces morphological and functional changes in animal liver, and abnormal liver and renal function studies have been reported in humans, so periodic urinalysis and liver function studies are advised for all patients. The label also instructs that patients be told before starting that a rash may herald a serious medical event.
Source
Ethosuximide United States prescribing information, Warnings (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The attention result is the most important finding and the least often quoted
In plain words
Ethosuximide and valproate control absence seizures equally well. The reason ethosuximide is first choice is not seizure control at all: it is that 33% of children on it had attentional problems against 49% on valproate.
What was measured
Percentage of children with attentional dysfunction at the month 12 visit, by treatment arm
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
On the primary seizure endpoint the two drugs were indistinguishable at both 16 weeks (53% against 58%, p=0.35) and 12 months (45% against 44%, p=0.82). The differentiating result is the secondary one: attentional dysfunction in 49% of children on valproic acid against 33% on ethosuximide (OR 1.95, 95% CI 1.12 to 3.41, p=0.03), a difference the 12-month report confirmed as persisting. The authors stated that these 12-month outcome data, coupled with the study prespecified decision-making algorithm, indicate that ethosuximide is the optimal initial empirical monotherapy. That conclusion rests on a secondary endpoint, in a trial powered for a primary one, and it is the right conclusion precisely because in this syndrome attention is not a side effect measure but the outcome the disease itself damages. Two limits are worth stating: attentional dysfunction at 33% on ethosuximide is not a small number in absolute terms, and the trial had no untreated arm, so how much of that 33% belongs to the drug rather than to the epilepsy cannot be separated.
Written into the record, not signed off as a reviewed claim
Eight products in the whole United States market, and a price that reflects it
In plain words
Ethosuximide is a tiny, simple, sixty-five-year-old molecule that costs a United States pharmacy about 25 cents a unit, more than carbamazepine or phenytoin. The likeliest reason is not chemistry but that only eight products are listed.
What was measured
Number of listed products and median per-unit acquisition cost, compared across this drug class
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The CMS National Average Drug Acquisition Cost file lists 8 ethosuximide products, against 29 for phenytoin, 92 for carbamazepine, 134 for levetiracetam and 158 for topiramate. The median acquisition cost is US$0.2483 per unit, above phenytoin at US$0.1812 and below carbamazepine at US$0.3776, for a molecule of 141 daltons with no chiral centre, made by a single cyclisation. Small-population generics with few manufacturers are a recognised structural weak point in drug supply, exposed both to price movement and to shortage when one manufacturer stops. This page states the observable facts, the product count and the acquisition cost, and does not estimate what the drug costs to make, because no verifiable per-dose production figure was found.
Source
CMS National Average Drug Acquisition Cost 2026 file, prices effective 19 August 2026, product counts compared across the anti-seizure drugs on these pages
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
5SEH9X1D1D
RxNorm concept
251322
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✗ Not passed
Safety mode resolved
No register row and no identity class settled the question.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
10 approved applications cover products containing this substance. The earliest was NDA012380, approved 19601102 to PARKE DAVIS.
This order is fixed in code and does not count clicks or time on the page.
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 1960 succinimide with a label whose mechanism paragraph predates the discovery of the channel it is now believed to block, which in 2010 became the subject of the first randomised trial in any generalised epilepsy to meet class I criteria: 53% freedom from treatment failure at 16 weeks against 58% for valproate and 29% for lamotrigine, with attentional dysfunction in 33% against 49% on valproate.
"Recruitment difficult and enrolment low: decision was made to stop the study."; 2 of 10 registered studies
Show the evidence
Trial
NCT00689585
terminated; "Recruitment difficult and enrolment low: decision was made to stop the study."
NCT01122381
terminated; "poor recruitment"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Which 4 trials of Ethosuximide posted no result?
Posted no result
4 of 4 completed trials
Registrations
NCT01278004, NCT03887624, NCT02973542 and NCT03196466
Completion dates
oldest 2014-07; newest 2023-06-15
Show the evidence
Trial
NCT01278004
2014-07
NCT03887624
2021-04-01
NCT02973542
2023-05-07
NCT03196466
2023-06-15
Q5
At the median, Ethosuximide's trials enrolled 62 people — anything larger?
Median enrolment
62
Largest enrolment
753
Registered trials counted
10
Q6
What do 250 spontaneous reports say about Ethosuximide — 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.
Ethosuximide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 250 reaction mentions were counted: seizure 42; aplastic anaemia 31; condition aggravated 26; convulsion 25. FAERS via Open Targets · CHEMBL696 · 2026-06-24
Show the evidence
seizure
42
aplastic anaemia
31
condition aggravated
26
convulsion
25
somnolence
25
epilepsy
22
4 more recorded rows
multiple-drug resistance
22
generalised tonic-clonic seizure
20
drug resistance
19
petit mal epilepsy
18
recorded 2026-06-24 · last checked 2026-09-04
Q7
Which 10 reactions does Ethosuximide's label not list?
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
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 5 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
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.