This page shows what was measured, who it was measured in, and what that does not settle.
What Topiramate does in the body
Topiramate does at least four different things at once and nobody has established which of them stops seizures.
It slows sodium pores in nerve membranes, it strengthens the brain main calming signal, it weakens one of the main excitatory signals, and it blocks an enzyme called carbonic anhydrase that handles acid and bicarbonate. That last one is not a brain effect at all: it is why the drug makes the blood slightly acidic, causes kidney stones and tingling in the hands, and is part of why people lose weight on it.
Why people take it. Epilepsy, including focal and generalised seizures and Lennox-Gastaut syndrome, and prevention of migraine attacks
What happened in people
Decreased serum bicarbonate in up to 67% of children in paediatric adjunctive trials, averaging a 4 mEq/L fall at 400 mg/day in adults
✎ 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.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
That the mechanism of topiramate is known: the label lists four candidate actions and states the precise mechanisms are unknown
Where it acts
Cortical neuron membranes and, for the carbonic anhydrase effects, the kidney tubule, eye and sweat gland as well
Kind of result
A number that stands in for health
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 · 0H73WJJ391 · read 2026-08-29
Its recorded molecular formula is C12H21NO8S, weighing 339.36.
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 130 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.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
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.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Body weight
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved5 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Mood
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Pain
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Body weight
body weight from baseline to week 24; body mass index; body weight; weight loss from baseline to week 28; at least 5 weight loss at week 28 locf
Mood
liebowitz social anxiety scale
Pain
therapeutic response to the analgesic drugs
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
5 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
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.
Time to first seizure during the double-blind phase, topiramate 400 mg/day against topiramate 50 mg/day
✓ The study showed what it set out to show
Who was studied
Monotherapy epilepsy Study 1 (label Clinical Studies 14.1)
Kaplan-Meier curves for time to first seizure favoured 400 mg/day over 50 mg/day; the label reports the comparison graphically rather than as a hazard ratio
Repeated elsewhere
Partially 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. The comparator is a sub-therapeutic dose of the same molecule. Patients unable to tolerate 150 mg/day were discontinued, and only 58% reached 400 mg/day for more than two weeks.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sprinkle capsule, extended-release capsule and oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
Co-primary: time to treatment failure and time to 12-month remission across five first-line drugs in focal epilepsy
✗ The study did not show it
Who was studied
SANAD arm A (ISRCTN38354748)
How many people
1721
Study design
Unblinded randomised controlled trial, five parallel arms
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Lamotrigine significantly better than topiramate for time to treatment failure, HR 0.64 (95% CI 0.52 to 0.79); carbamazepine non-significantly better for 12-month remission, HR 0.86 (0.72 to 1.03)
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. The gap between lamotrigine and topiramate on treatment failure was the largest of the trial, and treatment failure in an unblinded trial is a clinician decision as much as a drug property.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sprinkle capsule, extended-release capsule and oral solution
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
Co-primary: time to treatment failure and time to 12-month remission, valproate against lamotrigine and topiramate in generalised and unclassifiable epilepsy
✗ The study did not show it
Who was studied
SANAD arm B (ISRCTN38354748)
How many people
716
Study design
Unblinded randomised controlled trial, three parallel arms
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Valproate significantly better than topiramate for treatment failure, HR 1.57 (95% CI 1.19 to 2.08); in idiopathic generalised epilepsy HR 1.89 (1.32 to 2.70); no significant difference for 12-month remission
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 limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sprinkle capsule, extended-release capsule and oral solution
Interval reported. 95% CI 1
Written into the record, not signed off as a reviewed claim.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
Median reduction 72.2% at 100 mg/day against 44.4% on placebo, P=0.0164; 50 mg/day 44.6%, P=0.7975
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. The placebo group achieved a 44.4% median reduction on its own, which is why the 50 mg dose was indistinguishable from it.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sprinkle capsule, extended-release capsule and oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
RNAWiki holds 4 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 happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.4 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.11 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Rat. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
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
Topiramate
What a person takes: Oral tablet, sprinkle capsule, extended-release capsule and oral solution.
The measurement behind this step
The sprinkle capsule exists so a dose can be given to a child or to someone who cannot swallow tablets, and the extended-release capsules Trokendi XR and Qudexy XR are separate FDA applications rather than reformulations, taken once daily. There is no intravenous topiramate, so it has no role in acute seizure management. Titration rate is not a convenience question here: the label ties higher cognitive adverse reaction rates directly to rapid titration and higher starting doses.
Getting in
Swallowed, absorbed well, and mostly excreted unchanged
Absorption is rapid and nearly complete, and food does not matter much. Most of the drug leaves in the urine without being broken down, so kidney function governs how much stays in the body.
╌╌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
Bioavailability is high and largely food-independent. Protein binding is low. Clearance is predominantly renal, with hepatic metabolism a minor route unless an enzyme-inducing anti-seizure drug is present, in which case metabolism rises and topiramate exposure falls. Titration rate, not just dose, drives the cognitive adverse reaction rate.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
It reaches the brain, and also the kidney, eye and sweat gland
The molecule crosses into brain tissue, but it does not stay there. Carbonic anhydrase, one of its targets, sits in the kidney tubule, the eye and the sweat gland too, which is why several of its effects are not neurological at all.
╌╌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
Distribution is not brain-selective. Inhibition of carbonic anhydrase isozymes II and IV in renal tubule, ciliary body and eccrine gland accounts for the labelled warnings on metabolic acidosis, acute myopia with secondary angle closure glaucoma, oligohidrosis with hyperthermia and nephrolithiasis.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
It slows sodium pores, strengthens the calming GABA signal, weakens an excitatory glutamate signal, and blocks a bicarbonate enzyme. Which of these stops a seizure has never been settled.
╌╌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 label names blockade of voltage-dependent sodium channels, augmentation of GABA at some GABA-A receptor subtypes, antagonism of AMPA and kainate glutamate receptors, and inhibition of carbonic anhydrase II and IV, all at pharmacologically relevant concentrations, and states the precise mechanisms are unknown. No study apportions the clinical effect between them.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
The net effect on the brain is that it takes more to start and sustain a burst of firing. The net effect on the body is a mild, persistent shift towards acid.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Bicarbonate decrements average 4 mEq/L at 400 mg/day in adults and about 6 mg/kg/day in children, reaching 67% incidence in paediatric adjunctive trials, and rarely fall below 10 mEq/L. Conditions that predispose to acidosis, including renal disease, severe respiratory disorders, status epilepticus, diarrhoea and a ketogenic diet, add to the effect.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
Fewer seizures or fewer migraines, at a measured cognitive cost
For migraine at the recommended dose, about one fewer attack per four weeks than placebo. For epilepsy, effective but the drug people were most likely to stop in the largest first-line trial. Cognitive complaints reached 56% at the highest trial doses against 14% on placebo.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Efficacy is established against placebo in six adjunctive epilepsy trials, in Lennox-Gastaut syndrome and in two adult plus one adolescent migraine prevention trial. Efficacy against an active comparator has been tested in SANAD arms A and B, and topiramate finished behind lamotrigine and behind valproate respectively on time to treatment failure.
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · 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 it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
clinical global impression improvement 2
liebowitz social anxiety scale
global impression of change
physician global impression of change
Measured
Things only a test, a scale or a device shows.
body weight from baseline to week 24
body mass index
body weight
weight loss from baseline to week 28
at least 5 weight loss at week 28 locf
cmax maximum observed concentration
maximum plasma concentration
concentration of calcium in serum and random urine
concentration of bone specific alkaline phosphatase in serum
concentration of bicarbonate in serum
and 1 more.
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
safety as measured by the occurrence of adverse events
headache days per month on the third month of treatment
drinking days
cannabis use
cognition
therapeutic response to the analgesic drugs
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. 21 hours hours
Read from the label, which states: “The mean plasma elimination half-life is 21 hours after single or multiple doses. Steady-state is thus reached in about 4 days in patients with normal renal function.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
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.
People with focal or generalised epilepsy, children with Lennox-Gastaut syndrome, and a much larger group taking it to prevent migraine. It is also a component of the weight-loss combination phentermine-topiramate.
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: “Adjunctive Treatment for Partial Onset Epilepsy in Infants and Toddlers ( 1 to 24 months) Safety and effectiveness in patients below the age of 2 years have not been established for the adjunctive therapy treatment of partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome.”
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-30
On older people, the label states: “However, clinical studies of topiramate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.”
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-30
On people who are pregnant, the label states: “Category D [see Warnings and Precautions 5.7 ] Topiramate tablets can cause fetal harm when administered to a pregnant woman.”
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-30
On people who are breastfeeding, the label states: “Limited data on 5 breastfeeding infants exposed to topiramate showed infant plasma topiramate levels equal to 10–20% of the maternal plasma level.”
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-30
On people with reduced kidney function, the label states: “The clearance of topiramate was reduced by 42% in moderately renally impaired (creatinine clearance 30 to 69 mL/min/1.73m 2 ) and by 54% in severely renally impaired subjects (creatinine clearance <30 mL/min/1.73m 2 ) compared to normal renal function subjects (creatinine clearance >70 mL/min/1.73m 2 ).”
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-30
Where the result stopped carrying
It came out of a programme searching for antidiabetic sugar derivatives, and the anticonvulsant activity was an incidental finding rather than the objective
It finished behind lamotrigine in SANAD arm A and behind valproate in SANAD arm B, on the outcome that measures whether people can stay on a drug
The 50 mg dose failed to separate from placebo in the adolescent migraine trial, where placebo alone produced a 44.4% median reduction
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 for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
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 (10)
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 tablet, sprinkle capsule, extended-release 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
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.
No source is stored against this line.
What is in the pack
The sprinkle capsule exists so a dose can be given to a child or to someone who cannot swallow tablets, and the extended-release capsules Trokendi XR and Qudexy XR are separate FDA applications rather than reformulations, taken once daily.
✎ 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. The rest of the recorded wording: There is no intravenous topiramate, so it has no role in acute seizure management. Titration rate is not a convenience question here: the label ties higher cognitive adverse reaction rates directly to rapid titration and higher starting doses.
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.
The recorded stepping schedule
What follows is the schedule printed on the label, recorded as it is written there. It is a record of what was done, not a recommendation.
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Week 1: 25 mg morning dose; 25 mg evening dose — Label Table 1 monotherapy epilepsy titration schedule for adults and pediatric patients 10 years and older
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Week 2: 50 mg morning dose; 50 mg evening dose
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Week 3: 75 mg morning dose; 75 mg evening dose
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Week 4: 100 mg morning dose; 100 mg evening dose
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Week 5: 150 mg morning dose; 150 mg evening dose
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Week 6: 200 mg morning dose; 200 mg evening dose
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
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 an unusually long warnings list. Cognitive dysfunction is the defining problem, at 56% in the highest-dose adjunctive epilepsy arms against 14% on placebo. Carbonic anhydrase inhibition drives metabolic acidosis (up to 67% of children in paediatric trials), kidney stones, paraesthesia, reduced bone mineral density in children and oligohidrosis with hyperthermia. Acute myopia with secondary angle closure glaucoma typically appears within the first month and is treated by stopping the drug. Hyperammonaemia and encephalopathy can occur, more so with concomitant valproate, as can hypothermia. Oral clefts and small-for-gestational-age birth are labelled fetal risks. DRESS, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis and angioedema are all listed. The class-wide suicidality warning applies.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Topiramate United States prescribing information: Clinical Studies 14.1 to 14.3, Warnings and Precautions 5.1 to 5.16, Mechanism of Action 12.1, retrieved fr… · a recorded source, not a stored snapshot
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.
Topiramate appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4719 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
drug interaction — 589 reaction mentions
somnolence — 561 reaction mentions
convulsion — 530 reaction mentions
seizure — 513 reaction mentions
weight decreased — 497 reaction mentions
angle closure glaucoma — 474 reaction mentions
paraesthesia — 451 reaction mentions
migraine — 426 reaction mentions
cognitive disorder — 345 reaction mentions
nephrolithiasis — 333 reaction mentions
open-targets-adr · recorded 2026-06-24 · 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 tablet, sprinkle capsule, extended-release 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 intravenous topiramate, so it has no role in acute seizure management. Titration rate is not a convenience question here: the label ties higher cognitive adverse reaction rates directly to rapid titration and higher starting doses.
✎ 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
374 products list this as an active ingredient in the United States drug directory. 346 of them contain it and nothing else.
FDA National Drug Code directory · 71610-493 · read 2026-08-29
They are sold as bead, capsule, capsule, coated pellets, capsule, extended release, powder and solution, taken oral.
FDA National Drug Code directory · 71610-493 · read 2026-08-29
The regulator's established pharmacologic class for it is cytochrome p450 2c19 inhibitors [moa], cytochrome p450 3a4 inducers [moa] and decreased central nervous system disorganized electrical activity [pe].
FDA National Drug Code directory · 71610-493 · read 2026-08-29
162 published labels name it as an active ingredient. 158 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 2917ba32-3355-4d64-966a-8518e6fafdbe · read 2026-08-29
Topiramate is film-coated tablets at Tablets: 25 mg, 50 mg, 100 mg, and 200 mg, recorded as prescription product; fda label in effect 2026-06-08 in the United States.
US prescribing information · 021005ab-6a00-40d8-9aee-20c91613b4d5 · read 2026-08-27
Recorded price in US: 0.02563–4.34817 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 94 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: 1.0826–2.11842 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
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.
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 Topiramate 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 the mechanism of topiramate is known: the label lists four candidate actions and states the precise mechanisms are unknown
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 monotherapy efficacy was demonstrated against an alternative treatment, when the registration trial compared 400 mg with 50 mg of the same drug
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 raised crude autism rate in exposed children reflects a drug effect, when adjustment for indication removed almost all of it
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 cognitive complaints on this drug are the epilepsy or the migraine rather than the drug, when the label reports a clean dose-response against placebo
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 Topiramate 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.
Migraine prevention: about one fewer attack per four weeks than placebo
In plain words
Two identical placebo-controlled trials measured how many migraines people had before and during treatment. At the recommended 100 mg dose the drop was 2.1 attacks per four weeks against 1.1 on placebo. The benefit over placebo is one migraine a month.
What was measured
Mean change in 4-week migraine headache frequency from baseline, by dose, against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Studies 11 and 12 were multicentre randomised double-blind parallel-group trials in adults with at least six months of migraine by International Headache Society criteria, requiring 3 to 12 migraines in a 4-week baseline, randomised to topiramate 50, 100 or 200 mg/day or placebo for 26 weeks (8-week titration, 18-week maintenance). Mean change in 4-week migraine headache frequency from baseline was -1.4, -2.1 and -2.4 in the 50, 100 and 200 mg/day groups against -1.1 on placebo. The 100 and 200 mg differences from placebo were statistically significant (p=0.008 and p<0.001); the 50 mg difference was not. In the adolescent trial, Study 13, 103 patients aged 12 to 17 were randomised to 50 mg/day, 100 mg/day or placebo; median percentage reduction in monthly attacks was 72.2% at 100 mg against 44.4% on placebo (p=0.0164) while 50 mg was indistinguishable from placebo (p=0.7975).
Source
Topiramate United States prescribing information, Clinical Studies 14.3, Studies 11, 12 and 13 (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Cognitive dysfunction in 56% of patients at the doses used in the epilepsy trials
In plain words
Word-finding trouble, slowed thinking and memory problems are not rare on this drug and they are not imagined. In the adjunctive epilepsy trials 56% of patients on the highest doses reported them, against 14% on placebo. The rate tracks the dose and how fast the dose was raised.
What was measured
Incidence of cognitive-related adverse reactions by dose and titration rate, against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label reports that in adult adjunctive epilepsy controlled trials, which used rapid titration in 100 to 200 mg/day weekly increments to targets of 200 to 1,000 mg/day, 56% of patients in the 800 and 1,000 mg/day groups experienced cognitive-related dysfunction, against approximately 42% at 200 to 400 mg/day and 14% on placebo. In the monotherapy epilepsy controlled trial the rate was 19% at 50 mg/day and 26% at 400 mg/day. In the 6-month migraine trials, which titrated more slowly at 25 mg/day weekly increments, rates were 19% at 50 mg/day, 22% at 100 mg/day, 28% at 200 mg/day and 10% on placebo. The label groups the reactions as cognitive-related dysfunction (confusion, psychomotor slowing, concentration and memory difficulty, speech and language problems, particularly word-finding), psychiatric and behavioural disturbances, and somnolence or fatigue, and states that both rapid titration and higher initial dose were associated with higher incidences.
Source
Topiramate United States prescribing information, Warnings and Precautions 5.6 (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
SANAD focal arm: the largest tolerability gap in the trial, and it went against topiramate
In plain words
In 1,721 patients with focal epilepsy randomised across five drugs, lamotrigine beat topiramate on how long people stayed on their assigned drug by the widest margin of any comparison in the study.
What was measured
Time to treatment failure and time to 12-month remission across five drugs
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
SANAD arm A randomised 1,721 patients for whom carbamazepine was deemed standard treatment to carbamazepine, gabapentin, lamotrigine, oxcarbazepine or topiramate, with co-primary outcomes of time to treatment failure and time to 12-month remission. For time to treatment failure, lamotrigine was significantly better than topiramate (HR 0.64, 95% CI 0.52 to 0.79) and than gabapentin (0.65, 0.52 to 0.80) and carbamazepine (0.78, 0.63 to 0.97). For time to 12-month remission, carbamazepine held a non-significant advantage over topiramate (HR 0.86, 95% CI 0.72 to 1.03). The pattern is consistent with the label: topiramate is not a weak anti-seizure drug, it is a drug people stop taking.
Written into the record, not signed off as a reviewed claim
SANAD generalised arm: valproate was better, and worse in the syndrome that matters
In plain words
In 716 patients with generalised epilepsy, valproate beat topiramate on staying on treatment. Among the subgroup with genetic generalised epilepsy, the gap was larger still.
What was measured
Time to treatment failure and time to 12-month remission, valproate against lamotrigine and topiramate
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
SANAD arm B randomised 716 patients for whom valproate was considered standard treatment to valproate, lamotrigine or topiramate. For time to treatment failure, valproate was significantly better than topiramate (HR 1.57, 95% CI 1.19 to 2.08) while showing no significant difference from lamotrigine (1.25, 0.94 to 1.68). Restricted to idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55, 1.07 to 2.24) and topiramate (1.89, 1.32 to 2.70). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76, 0.62 to 0.94) but showed no significant difference from topiramate in either the overall analysis or the idiopathic generalised subgroup. The authors concluded valproate should remain the drug of first choice for many patients with generalised and unclassified epilepsies, while noting the pregnancy problem that makes that conclusion hard to act on.
Written into the record, not signed off as a reviewed claim
The monotherapy licence rests on 400 mg of topiramate against 50 mg of topiramate
In plain words
The trial that established topiramate as a stand-alone first drug compared a high dose with a low dose of the same drug. It shows more works better than less. It does not show the drug works better than an alternative.
What was measured
Time to first seizure, 400 mg/day against 50 mg/day of the same drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study 1 was a multicentre randomised double-blind parallel-group trial in 487 patients aged 6 to 83 with 1 or 2 documented seizures in a 3-month retrospective baseline; 470 were randomised in the double-blind phase to titrate to 50 mg/day or 400 mg/day, with maintenance at the maximum tolerated dose. Forty-nine percent had no prior anti-seizure treatment. Fifty-eight percent reached 400 mg/day for more than two weeks, and patients who could not tolerate 150 mg/day were discontinued. The primary assessment was a between-group comparison of time to first seizure, and the Kaplan-Meier curves favoured 400 mg over 50 mg. The paediatric monotherapy conclusion for ages 2 to 9 was reached by a pharmacometric bridging approach rather than by a trial in that age group at all. SANAD supplied the missing active comparison seven years later, and topiramate lost it.
Source
Topiramate United States prescribing information, Clinical Studies 14.1, Study 1 (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
Metabolic acidosis in up to 67% of children, and thinner bones alongside it
In plain words
Blocking carbonic anhydrase makes the kidney lose bicarbonate, so the blood turns slightly acidic. In paediatric epilepsy trials this happened in as many as two thirds of children, and a bone-density study found measurable losses that tracked the acidosis.
What was measured
Incidence of decreased serum bicarbonate and proportion with a bone mineral density Z-score change of -0.5 or greater
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that topiramate causes hyperchloraemic, non-anion-gap metabolic acidosis by renal bicarbonate loss due to carbonic anhydrase inhibition, that it can occur at any time during treatment, that decrements average 4 mEq/L at 400 mg/day in adults and about 6 mg/kg/day in children, and that rare patients fall below 10 mEq/L. Incidence of decreased serum bicarbonate in paediatric adjunctive trials for Lennox-Gastaut syndrome or refractory partial-onset seizures reached 67%. A separate one-year active-controlled paediatric study (N=63) found statistically significant decreases in lumbar spine and total-body-less-head bone mineral density, with 21% of topiramate-treated patients showing a Z-score change of -0.5 or greater against 0 patients in the control group, most commonly in children aged 6 to 9, and decreased lumbar spine density correlated with decreased serum bicarbonate. The label notes the study was too small and too short to say whether fracture risk rises.
Source
Topiramate United States prescribing information, Warnings and Precautions 5.4 and 5.9 (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The autism signal did not survive adjustment for why the drug was prescribed
In plain words
Children exposed to topiramate before birth do have more autism diagnoses than the general population. Once the comparison was made against children of mothers with epilepsy who took nothing, and adjusted for confounders, the topiramate association essentially vanished. The valproate one did not.
What was measured
Propensity-score-adjusted hazard ratio for autism spectrum disorder by age 8, against unexposed children of mothers with epilepsy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hernandez-Diaz and colleagues assembled a population-based cohort from two United States healthcare databases covering 2000 to 2020, defining exposure by prescription fills from gestational week 19 to delivery. Cumulative incidence of autism spectrum disorder at age 8 was 1.9% among 4,199,796 children unexposed to any anti-seizure medication. Restricted to children of mothers with epilepsy it was 4.2% with no exposure (8,815 children), 6.2% with topiramate (1,030), 10.5% with valproate (800) and 4.1% with lamotrigine (4,205). Propensity-score-adjusted hazard ratios against no exposure were 0.96 (95% CI 0.56 to 1.65) for topiramate, 1.00 (0.69 to 1.46) for lamotrigine and 2.67 (1.69 to 4.20) for valproate. The authors used valproate as a positive control and lamotrigine as a negative control, which is what makes the null result for topiramate interpretable rather than merely underpowered. This changes nothing about the oral cleft risk, which is a separate, structural, first-trimester endpoint and remains on the label.
Written into the record, not signed off as a reviewed claim
Oral clefts and small-for-gestational-age babies are on the label
In plain words
Registry data show more cleft lip and cleft palate, and more underweight newborns, after topiramate exposure in pregnancy. The malformation rate in the EURAP registry was 3.9%, but that figure rests on only 152 pregnancies.
What was measured
Registry-reported prevalence of major congenital malformations, oral clefts and small-for-gestational-age status after in-utero exposure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Warnings and Precautions 5.7 states that topiramate can cause fetal harm, that pregnancy registry data show an increased risk of major congenital malformations including but not limited to cleft lip and cleft palate and of being small for gestational age, and that structural malformations including craniofacial defects and reduced fetal weights occurred in multiple animal species at clinically relevant doses. The label adds a specific instruction to weigh the risk when topiramate is considered for a condition not usually associated with permanent injury or death, which is a direct reference to migraine prevention. In EURAP, major congenital malformation prevalence at one year for topiramate monotherapy was 6 of 152 (3.9%), the smallest denominator of the eight drugs compared and therefore the least precise estimate in that study.
Written into the record, not signed off as a reviewed claim
Four mechanisms are listed. None is established, and one explains the side effects better than the benefit.
In plain words
The label names four things topiramate does and then says the precise mechanisms are unknown. The one with the cleanest laboratory measurement, blocking carbonic anhydrase, is the one that best explains the acidosis, the stones and the tingling rather than the seizure control.
What was measured
That listing four plausible molecular actions amounts to knowing how the drug works. The label itself declines to make that claim.
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mechanism of Action 12.1 states that the precise mechanisms by which topiramate exerts its anticonvulsant and preventive migraine effects are unknown, then lists four preclinical properties at pharmacologically relevant concentrations: blockade of voltage-dependent sodium channels, augmentation of GABA activity at some GABA-A receptor subtypes, antagonism of the AMPA and kainate subtype of the glutamate receptor, and inhibition of carbonic anhydrase, particularly isozymes II and IV. No published work assigns a share of the clinical effect to any one of them. The carbonic anhydrase activity, by contrast, has a clear and traceable chain to observable consequences: renal bicarbonate loss, hyperchloraemic non-anion-gap acidosis, raised urine pH, kidney stones, paraesthesia, reduced bone mineral density and part of the weight loss. A mechanism that predicts the harms well and the benefit not at all is a mechanism that has not been shown to be the mechanism.
Source
Topiramate United States prescribing information, Mechanism of Action 12.1 and Warnings and Precautions 5.4 and 5.15 (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
How many documents were read
155 documents were read for this substance.
RNAWiki source record
134 of them state the same bioavailability, and they agree.
RNAWiki source record
155 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
0H73WJJ391
CAS registry number
97240-79-4
PubChem compound
5284627
RxNorm concept
38404
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
✓ Passed
Safety mode resolved
Suppression classes recorded: S3.
✓ 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
60 approved applications cover products containing this substance. The earliest was NDA020505, approved 19961224 to JANSSEN PHARMS.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 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 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 sulfamate sugar derivative with four separate proposed mechanisms and no established one, which reduced migraine frequency by about one attack per four weeks more than placebo at the recommended 100 mg dose, lost to lamotrigine on treatment failure in SANAD focal arm (HR 0.64 favouring lamotrigine) and to valproate in the generalised arm (HR 1.57), and whose cognitive side effects reached 56% of patients at the doses used in its adjunctive epilepsy trials against 14% on placebo.
Recorded evidence blocks (13)
Q2
What did Topiramate's largest trial (3300 people) and its longest (17 years) measure?
3300 people in Topiramate's largest registered study, 17 years in its longest registered window, measuring Individual (each patient) and mean (each treatment) topiramate plasma concentration-time profiles. ClinicalTrials.gov · 2026-09-01
68 phase3, 57 phase2, 50 phase4, 28 phase1, 18 na, 11 na or unstated, 4 early phase1; NCT00182520; 2019-01; no ageing endpoint recorded. Last human test completed 2026, NCT05748483.
Interpretation These counts include studies where Topiramate was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase3
68
phase2
57
phase4
50
phase1
28
na
18
na or unstated
11
2 more recorded rows
early phase1
4
Last recorded human testNCT05748483
2026-06-02
recorded 2026-09-01 · last checked 2026-09-04
Q3
From rat to human: where has Topiramate shown biomarker?
15 recorded entries; human; also "Topiramate Sprinkle Capsules 25 mg", "Topamax® Sprinkle Capsules 25 mg", "Topamax® Sprinkle Capsule 25 mg"
Show the evidence
human
NCT00648934
Topiramate Sprinkle Capsules 25 mg
NCT00648934
Topamax® Sprinkle Capsules 25 mg
NCT00649740
Topamax® Sprinkle Capsule 25 mg
NCT00884884
Topiramate 100, Aripiprazole 15mg
NCT00884884
Topiramate 200, Aripiprazole 7.5mg
NCT00904943
Topiramate Capsules, 25 mg
9 more recorded rows
humanNCT00904943
Topamax® Capsules, 25 mg
humanNCT00905346
Topiramate 25 mg Capsules
humanNCT00905346
Topamax® 25 mg Capsules
humanNCT01889602
Topiramate 100mg
humanNCT01889602
Topiramate 150mg
humanNCT01889602
Topiramate 200mg
humanNCT02403687
Topiramate 2.5%
humanNCT06248931
Topiramate 50 MG
humanNCT06972056
Topiramate 100 mg
recorded 2026-09-01 · last checked 2026-09-04
Q6
More Topiramate was worse in human: at what point?
U-shaped in human: "Subsequently, Topiramate produced an inverted U-shaped dose response curve, with increases in aggression at low doses, whereas higher doses engendered anti-aggressive effects." Europe PMC · dose-response search · 2023-01-13
5 recorded sentences naming Topiramate; U-shaped, dose-response
Show the evidence
U-shapedPMID 32810566
"Subsequently, Topiramate produced an inverted U-shaped dose response curve, with increases in aggression at low doses, whereas higher doses engendered anti-aggressive effects."
dose-response
PMID 36731257
"Significantly lower scores were observed in topiramate-exposed children (n = 21) with a significant dose-response relationship established after adjustment for parental educational level."
PMID 36211148
"The relative risk of paresthesia is higher with the use of Topiramate 200 mg, Lasmiditan 400 mg, and Zolmitriptan 10 mg. In addition, Lasmiditan exhibited a gradual dose-response of relative risk for the manifestation of paresthesia."
PMID 32810566
"In our previous study, we demonstrated that Topiramate modulates brain activity in the prefrontal areas involved in the modulation of the subcortical circuit mediating aggression, and we found indirect evidence that the anterior cingulate cortex (ACC) could be a key site where Topiramate may exert its dose-response effects on aggression."
PMID 32810566
"Therefore, we suggest that the ACC is a key brain region in which Topiramate may exert its dose-response effects on aggressive and antisocial behaviors observed in populations with psychotic disorders."
recorded 2023-01-13 · last checked 2026-09-04
Q7
Topiramate's half-life is 21 hours — which schedules were studied?
21 hours, the half-life Topiramate's label states. openfda-label · 59f39dea-f29b-d6c6-e063-6294a90a5b74 · 2026-08-27
bioavailability about 80% relative to a solution (tablet formulation) %.
Show the evidence
half life
21 hours hours; The mean plasma elimination half-life is 21 hours after single or multiple doses. Steady-state is thus reached in about 4 days in patients with normal renal function.
tmax
Topiramate did not affect metformin t max. The clinical significance of the effect of topiramate on metformin pharmacokinetics is not known.
bioavailability
about 80% relative to a solution (tablet formulation) %; The relative bioavailability of topiramate from the tablet formulation is about 80% compared to a solution. The bioavailability of topiramate is not affected by food.
metabolism
Metabolism and Excretion Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose).
recorded 2026-08-27 · last checked 2026-09-04
Q8
Which of abstinence, adverse events and alcohol use did Topiramate's trials measure?
abstinence, adverse events and alcohol use lead 40 outcome terms across Topiramate's trials. ClinicalTrials.gov · 2026-09-01
clinical global impression improvement 2, liebowitz social anxiety scale, yale brown obsessive compulsive scale, drug safety, body weight from baseline to week 24 and abstinence follow.
Show the evidence
seizure frequency
1
responders
1
heavy drinking days
1
clinical global impression improvement 2
1
liebowitz social anxiety scale
1
yale brown obsessive compulsive scale
1
14 more recorded rows
drug safety
1
body weight from baseline to week 24
1
abstinence
1
y bocs
1
body mass index
1
body weight
1
pharmacokinetic parameters
1
drinks per day
1
drinks per drinking day
1
days abstinent
1
weight loss from baseline to week 28
1
at least 5 weight loss at week 28 locf
1
adverse events
1
heavy drinking days per week by medication group
1
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which of Topiramate's 12 ongoing trials reports first?
"Topiramate and Schizophrenia: Effects on Weight and Psychopathology"; n 50; "Weight loss"; 2026-08
NCT03511118
"Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants"; n 1600; "M/P ratio"; 2028-07-31
NCT03667846
"Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With PTSD"; n 150; "Measure of Time-line Follow-back (TLFB)"; 2025-08-31
NCT04748601
"Qudexy XR for the Prevention of Migraine in Children 6 to 11 Years Old"; n 132; "Change from Baseline (last 28 days Run-In Period) in the monthly number of headache days during the 8-week Maintenance Period based on the diary."; 2026-09
NCT05756764
"Anti-obesity Pharmacotherapy and Inflammation"; n 30; "weight loss"; 2026-02-20
NCT05975580
"Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery"; n 120; "Percent weight loss at Month 12 - Topiramate vs placebo"; 2028-01-31
6 further recorded trials
NCT06499116
"Comparison of the Effectiveness of First-line Preventive Treatment of Migraine in Primary Care"; n 460; "To evaluate the effectiveness of the most frequently used drugs in primary care for the preventive treatment of migraine according to the reduction in monthly migraine days, comparing amitriptyline, flunarizine and topiramate with…"; 2026-12
NCT06799169
"Management of Acute Tinnitus With Migraine Medications"; n 100; "Tinnitus Functional Index"; 2026-12
NCT06972056
"Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study"; n 1335; "Treatment Responder (atogepant vs. topiramate; atogepant vs. propranolol)"; 2029-12-01
NCT07058155
"Optimizing Portal Hypertension With TIPS and Interval Metabolic Surgery for Advanced Liver Disease"; n 70; "Change in SF-36 Physical Component Summary (PCS) Score From Baseline to 6 Months"; 2034-02-01
NCT07384624
"Combining Latency Reversing Agents to Address the HIV Reservoir"; n 30; "Phase I primary outcome: Fold change in cell-associated HIV-RNA"; 2028-07
NCT07655440
"Comparing Migraine Preventive Therapies vs. Anti-CGRP Therapies for Tinnitus in Patients With Migraine (COMPACT-PM)"; n 120; "Change in Tinnitus Functional Index (TFI) Score"; 2031-07
recorded 2026-09-01 · last checked 2026-09-04
Q10
Which 94 trials of Topiramate posted no result?
Posted no result
94 of 94 completed trials
Registrations
NCT00236691, NCT00236730, NCT00236860, NCT00236873, NCT00236847 and NCT00236418, and 88 more
Completion dates
oldest 1990-12; newest 2024-06-30
Show the evidence
Trial
NCT00236691
1990-12
NCT00236730
1990-12
NCT00236860
1992-02
NCT00236873
1993-05
NCT00236847
1993-07
NCT00236418
1996-12
14 further recorded trials
NCT00266591
1997-04
NCT00236704
1999-12
NCT00236886
2000-06
NCT00236743
2000-10
NCT00236756
2001-02
NCT00236613
2001-07
NCT00901784
2001-10
NCT00902473
2001-10
NCT00253175
2001-12
NCT00231608
2002-01
NCT00035802
2002-04
NCT00231530
2002-05
NCT00236626
2002-05
NCT00231660
2002-06
Q11
At the median, Topiramate's trials enrolled 68 people — anything larger?
Median enrolment
68
Largest enrolment
3300
Registered trials counted
221
Q12
What do 4719 spontaneous reports say about Topiramate — 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.
Topiramate appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4719 reaction mentions were counted: drug interaction 589; somnolence 561; convulsion 530; seizure 513. open-targets-adr · CHEMBL220492 · 2026-06-24
Show the evidence
drug interaction
589
somnolence
561
convulsion
530
seizure
513
weight decreased
497
angle closure glaucoma
474
4 more recorded rows
paraesthesia
451
migraine
426
cognitive disorder
345
nephrolithiasis
333
recorded 2026-06-24 · last checked 2026-09-04
Q13
Was Topiramate studied with fasting?
fasting is named in Topiramate's label sentences: "The results of meta-analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15…" openfda-label+europepmc · 2016-01-01
1 recorded statement; fasting
Show the evidence
fasting
The results of meta-analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15 (95%CI: -1.50--0.79), P<0.000 01); but can not regulate the lipid metabolic disorders (Cholesterol:…
recorded 2016-01-01 · last checked 2026-09-04
Q14
What is recorded about Topiramate and mTOR?
"In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway." — where Topiramate and mTOR appear together. Europe PMC · pathway abstract search · 2023-08-29
mTOR, AMPK, autophagy; PMID 37765022, 34118646
Show the evidence
mTORPMID 37765022
"In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway."
AMPKPMID 37765022
"In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway."
autophagyPMID 37765022
"In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway."
mTORPMID 34118646
"Topiramate improved the body weight gain, decreased serum CEA, augmented the antioxidant defenses in the colonic tissues with significant amelioration of the inflammatory changes, decline in tissue VEGF and p-AKT/mTOR/MAP kinase signaling and increased Nrf2/HO-1 content in a dose-dependent manner when compared to rats treated with azoxymethane alone."
recorded 2023-08-29 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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