This page shows what was measured, who it was measured in, and what that does not settle.
What Lamotrigine does in the body
Several forms of epilepsy and long-term prevention of bipolar episodes.
Nerve cells fire by briefly opening sodium channels. Lamotrigine sticks to those channels once they have already fired and are resting, so a cell that is firing over and over recovers more slowly. Ordinary single signals get through; the rapid repetitive bursts that make up a seizure do not build as easily. Less of the excitatory messenger glutamate is released as a result.
What happened in people
People with focal epilepsy stayed on lamotrigine longer than several alternatives, although carbamazepine reached seizure freedom slightly sooner.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Staying on treatment longer does not necessarily mean seizures stopped sooner.
Where it acts
Axonal and presynaptic membrane of cortical neurons (voltage-gated sodium channels)
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · U3H27498KS · read 2026-08-29
Its recorded molecular formula is C9H7N5Cl2, weighing 256.1.
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 93 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.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
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 treatment failure and time to 12-month remission
✓ The study showed what it set out to show
Who was studied
SANAD arm A (ISRCTN38354748)
How many people
1721
Study design
Unblinded randomised controlled trial, five arms
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Time to treatment failure HR 0.78 (95% CI 0.63 to 0.97) versus carbamazepine, 0.65 (0.52 to 0.80) versus gabapentin, 0.64 (0.52 to 0.79) versus topiramate
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. On the co-primary outcome of time to 12-month remission, carbamazepine held a non-significant advantage over lamotrigine (HR 0.91, 0.77 to 1.09). The headline is from the other endpoint.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, chewable dispersible tablet, orally disintegrating tablet and extended-release tablet
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Response on the Hamilton and Montgomery-Asberg depression rating scales
✓ The study showed what it set out to show
Who was studied
Pooled individual patient data, five acute bipolar depression trials
How many people
1072
Study design
Independent meta-analysis of randomised placebo-controlled trials
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
HRSD response RR 1.27 (95% CI 1.09 to 1.47, p=0.002); interaction by severity p=0.04, with RR 1.07 (0.90 to 1.27, p=0.445) at HRSD 24 or below
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 individual trials were largely negative on their own primary endpoints; the effect appears only on pooling, and only at the severe end.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, chewable dispersible tablet, orally disintegrating tablet and extended-release tablet
Interval reported. 95% CI 1
Written into the record, not signed off as a reviewed claim.
HR 0.84 (95% CI 0.67 to 1.06); 7.0 versus 8.2 events per 1,000 person-years
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. `endpoint met: false` here means the hypothesised harm was not found. Risk was significantly lower on lamotrigine in the subgroups with baseline arrhythmia and with antiarrhythmic use.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, chewable dispersible tablet, orally disintegrating tablet and extended-release tablet
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 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
Lamotrigine
What a person takes: Oral tablet, chewable dispersible tablet, orally disintegrating tablet and extended-release tablet.
The measurement behind this step
There is no intravenous form, and the drug cannot be brought to an effective level quickly, because the rash risk rises with how fast the dose is escalated. That single constraint explains most of where lamotrigine is and is not used: it is a drug for planned long-term treatment, not for an emergency.
Getting in
Absorbed almost completely and cleared by a sugar-attaching enzyme
Nearly all of a swallowed tablet reaches the blood. The liver disposes of it by sticking a sugar group on, which is a different route from the one most other epilepsy drugs use.
──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
Oral bioavailability about 98%, unaffected by food, with roughly 55% plasma protein binding. Elimination is by glucuronidation, principally UGT1A4, to the inactive 2-N-glucuronide. Valproate inhibits that enzyme and roughly doubles exposure; carbamazepine, phenytoin, rifampicin and oestrogen-containing contraceptives induce it and roughly halve exposure.
The molecule crosses into brain tissue and settles where nerve cells generate their electrical signals, along the fibre that carries the signal onward.
╌╌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
Lipophilic enough for rapid blood-brain barrier passage. The relevant compartment is the axonal and presynaptic membrane, where voltage-gated sodium channel alpha subunits cluster at densities high enough to sustain repetitive firing.
The drug prefers channels in their spent, inactivated state over resting ones. A neuron firing at ordinary rates keeps most of its channels resting; a neuron firing in a seizure does not.
╌╌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
State-dependent binding to the inactivated conformation of the channel prolongs recovery from inactivation. The result is use-dependent and voltage-dependent block: potency rises steeply with depolarisation and with firing frequency, which is why the effect is selective for pathological activity rather than a general dampening.
Repetitive firing collapses and less glutamate is released
A long burst of firing runs out of available channels and stops. Because the burst is what drives release of the brain excitatory messenger, less of that messenger comes out.
╌╌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
Sustained repetitive firing is suppressed at concentrations that leave single action potentials intact. Downstream, presynaptic release of glutamate and aspartate falls, measurable as reduced veratridine-evoked release from cortical synaptosomes. The label describes this as one proposed mechanism whose relevance in humans remains to be established.
Fewer seizures, and in bipolar I disorder a longer gap before the next episode
In epilepsy the measured result is 12-month seizure freedom, achieved by more people than on levetiracetam or zonisamide. In bipolar I disorder it is 197 days to the next mood episode against 86 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
The mood-stabilising effect has no established mechanistic account. The bipolar licence is for maintenance to delay mood episodes; efficacy in an acute depressive episode is confined to the severely depressed in pooled individual-patient data.
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.
One of the two most commonly chosen first drugs for focal epilepsy in the United Kingdom and much of Europe, and a maintenance drug in bipolar I disorder. It is also the anti-seizure drug most often chosen in pregnancy.
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: “Lamotrigine extended-release tablets are indicated as adjunctive therapy for PGTC and partial-onset seizures with or without secondary generalization in patients aged 13 years and older.”
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
On older people, the label states: “Clinical trials of lamotrigine extended-release tablets for epilepsy did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients or exhibit a different safety profile than that of younger patients.”
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
On people who are pregnant, the label states: “In a study in which pregnant rats were administered lamotrigine (oral doses of 0, 5, or 25 mg/kg) during the period of organogenesis and offspring were evaluated postnatally, neurobehavioral abnormalities were observed in exposed offspring at both doses.”
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Lamotrigine is present in milk from lactating women taking lamotrigine extended-release tablets (see Data) .”
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
On people with reduced liver function, the label states: “Experience in patients with hepatic impairment is limited.”
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
On people with reduced kidney function, the label states: “Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine.”
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-30
Where the result stopped carrying
Four of the five individual acute bipolar depression trials did not meet their own primary endpoints; the effect emerged only in pooled individual patient data
The rash risk forced a slow introduction schedule that remains the drug practical limitation, and made co-prescription with valproate a documented hazard
The 2020 FDA cardiac label change was made on in vitro evidence and has not been revised despite two clinical datasets pointing the other way
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.
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: S6.
No source is stored against this line.
What is in the pack
There is no intravenous form, and the drug cannot be brought to an effective level quickly, because the rash risk rises with how fast the dose is escalated. That single constraint explains most of where lamotrigine is and is not used: it is a drug for planned long-term treatment, not for an emergency.
✎ 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.
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 · 003663e5-c0c7-4fc1-a64d-313f2a5b10d2 · read 2026-08-27
Weeks 1 and 2: 25 mg every day — Escalation regimen recorded for patients older than 12 years not taking carbamazepine, phenytoin, phenobarbital, primidone, or valproate
US prescribing information · 003663e5-c0c7-4fc1-a64d-313f2a5b10d2 · read 2026-08-27
Weeks 3 and 4: 50 mg/day
US prescribing information · 003663e5-c0c7-4fc1-a64d-313f2a5b10d2 · read 2026-08-27
Week 5 onward to maintenance: Increase by 50 mg/day every 1 to 2 weeks.
US prescribing information · 003663e5-c0c7-4fc1-a64d-313f2a5b10d2 · 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
A boxed warning for serious skin rashes, including Stevens-Johnson syndrome, at roughly 0.3% in adults and 0.8% in children on adjunctive therapy. Other labelled risks are haemophagocytic lymphohistiocytosis, DRESS, blood dyscrasias, aseptic meningitis, the class suicidality warning, and cardiac rhythm and conduction abnormalities based on in vitro findings. The label also warns about medication errors from product name confusion. Common effects are dizziness, headache, diplopia, ataxia and nausea.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
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
That single constraint explains most of where lamotrigine is and is not used: it is a drug for planned long-term treatment, not for an emergency.
✎ 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
325 products list this as an active ingredient in the United States drug directory. 325 of them contain it and nothing else.
FDA National Drug Code directory · 72888-028 · read 2026-08-29
They are sold as powder, suspension, tablet, tablet, chewable, tablet, extended release and tablet, film coated, extended release, taken oral.
FDA National Drug Code directory · 72888-028 · read 2026-08-29
The regulator's established pharmacologic class for it is anti-epileptic agent [epc], decreased central nervous system disorganized electrical activity [pe] and dihydrofolate reductase inhibitors [moa].
FDA National Drug Code directory · 72888-028 · read 2026-08-29
113 published labels name it as an active ingredient. 113 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 4bd7193f-a81a-4909-90c2-7f324fc6ddfd · read 2026-08-29
5 marketed supplement labels list this ingredient, classed as other combinations and vitamin.
Those labels carry all other and nutrient claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Lamotrigine is orally disintegrating tablets at 25 mg, 50 mg, 100 mg, and 200 mg, recorded as prescription product; fda label in effect 2026-04-22 in the United States.
US prescribing information · 003663e5-c0c7-4fc1-a64d-313f2a5b10d2 · read 2026-08-27
Recorded price in US: 0.02705–0.16123 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 88 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 Lamotrigine 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 lamotrigine stops focal seizures better than carbamazepine: it won on treatment failure, and carbamazepine held a non-significant edge on 12-month remission
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 in vitro cardiac sodium-channel effect translates into clinical arrhythmia, which two subsequent clinical datasets did not find
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 lamotrigine treats acute bipolar depression generally, when the pooled effect is confined to baseline Hamilton scores above 24
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a low malformation rate in a registry proves safety, when drug choice in EURAP and NEAD was not randomised
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 Lamotrigine 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.
SANAD: better than carbamazepine on treatment failure across 1,721 patients
In plain words
In the largest head-to-head trial of first drugs for focal epilepsy, patients on lamotrigine were less likely to stop the drug, for any reason, than patients on carbamazepine, gabapentin or topiramate.
What was measured
Time to treatment failure for any reason
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SANAD arm A was an unblinded randomised trial in UK outpatient clinics that assigned 1,721 patients for whom carbamazepine was standard treatment to carbamazepine, gabapentin, lamotrigine, oxcarbazepine or topiramate. For time to treatment failure, lamotrigine was significantly better than carbamazepine (HR 0.78, 95% CI 0.63 to 0.97), gabapentin (0.65, 0.52 to 0.80) and topiramate (0.64, 0.52 to 0.79), with a non-significant advantage over oxcarbazepine (1.15, 0.86 to 1.54). The per-protocol difference in the proportion achieving 12-month remission at 2 and 4 years was 0 (-8 to 7) and 5 (-3 to 12) percentage points, which the authors read as non-inferiority.
Written into the record, not signed off as a reviewed claim
Winning on treatment failure is not the same measurement as stopping seizures
In plain words
Lamotrigine won SANAD on how long people stayed on it. On how quickly people became seizure-free for a year, carbamazepine was slightly ahead, though not significantly so.
What was measured
That lamotrigine controls focal seizures better than carbamazepine, when what the trial showed is that fewer people stop taking it
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the same trial, for time to 12-month remission carbamazepine was significantly better than gabapentin (HR 0.75, 95% CI 0.63 to 0.90), and held non-significant advantages over lamotrigine (0.91, 0.77 to 1.09), topiramate (0.86, 0.72 to 1.03) and oxcarbazepine (0.92, 0.73 to 1.18). Time to treatment failure is a composite of inadequate seizure control and unacceptable adverse effects, so a drug can win it by being better tolerated while controlling seizures no better. The authors framed the conclusion in exactly those terms: lamotrigine is clinically better for treatment-failure outcomes and is therefore a cost-effective alternative.
Written into the record, not signed off as a reviewed claim
SANAD II: beat both newer comparators on per-protocol remission and on cost
In plain words
Fourteen years later the same group tested lamotrigine against levetiracetam and zonisamide in 990 newly diagnosed patients. Neither newer drug matched it, and lamotrigine caused fewer adverse reactions than either.
What was measured
Time to 12-month remission, intention-to-treat and per-protocol, plus adverse-reaction rate and QALYs
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SANAD II randomised 990 participants aged 5 and over 1:1:1 to lamotrigine (n=330), levetiracetam (n=332) or zonisamide (n=328), with a non-inferiority limit of HR 1.329 for time to 12-month remission. Levetiracetam failed non-inferiority (HR 1.18, 97.5% CI 0.95 to 1.47); zonisamide met it (1.03, 0.83 to 1.28). The per-protocol analysis showed 12-month remission superior with lamotrigine over both levetiracetam (HR 1.32, 1.05 to 1.66) and zonisamide (1.37, 1.08 to 1.73). Adverse reactions were reported by 33% starting lamotrigine, 44% starting levetiracetam and 45% starting zonisamide. Net health benefit was 1.403 QALYs for lamotrigine against 1.222 and 1.232.
Written into the record, not signed off as a reviewed claim
The boxed warning: serious rash in 3 adults and 8 children per 1,000
In plain words
The reason lamotrigine has to be started slowly is a rash that can strip skin. It sent about 8 in 1,000 treated children to hospital, and one child in a cohort of 1,983 died of it.
What was measured
Incidence of serious rash requiring hospitalisation, by age group and by valproate co-therapy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The United States label carries a boxed warning for serious skin rashes requiring hospitalisation and discontinuation. Incidence is approximately 0.8% (8 per 1,000) in paediatric patients aged 2 to 16 on adjunctive therapy and 0.3% (3 per 1,000) in adults on adjunctive therapy. In a prospectively followed cohort of 1,983 children, 16 serious rashes occurred and there was 1 rash-related death; when 14 of those cases were reviewed by three expert dermatologists, one classified none as Stevens-Johnson syndrome and another classified 7 of 14 as such. Concomitant valproate raised the paediatric rate to 1.2% (6 of 482) against 0.6% (6 of 952) without it. Nearly all life-threatening rashes occurred within 2 to 8 weeks. The presence of HLA-B*1502 is listed as a risk factor.
Source
LAMICTAL and LAMICTAL XR United States prescribing information, Boxed Warning and Warnings and Precautions 5.1 (Drugs@FDA NDA 020241, NDA 022115)
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 cardiac arrhythmia warning was built from in vitro data, and the clinical data do not support it
In plain words
In 2020 the FDA added a warning that lamotrigine could cause dangerous heart rhythms in people with heart disease. It was based on cell experiments. Two later studies in real patients found no such effect.
What was measured
That an in vitro sodium-channel effect on cardiomyocytes predicts clinical arrhythmia in patients, an extrapolation two subsequent clinical datasets did not reproduce
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that "based on in vitro findings" lamotrigine could cause serious arrhythmias or death in patients with certain underlying cardiac disorders. A retrospective Medicare cohort of individuals aged 65 and over with epilepsy compared 11,786 new lamotrigine users with 147,130 new levetiracetam users using inverse probability of treatment weighting; incidence of inpatient or emergency ventricular arrhythmia or sudden cardiac arrest was 7.0 against 8.2 per 1,000 person-years (HR 0.84, 95% CI 0.67 to 1.06), with significantly reduced risk in the subgroups with baseline arrhythmia (0.51, 0.32 to 0.80) or antiarrhythmic use (0.67, 0.50 to 0.91). A separate within-person study of 237 people with an ECG both on and off lamotrigine found a mean 3.1% increase in PR interval with no increase in the prevalence of pathological PR, QRS or QTc prolongation, in people with and without heart disease. The label has not been revised.
Written into the record, not signed off as a reviewed claim
Bipolar maintenance: 197 days to the next mood episode against 86 on placebo
In plain words
In two trials pooled together, patients stabilised after a manic or depressive episode were kept on lamotrigine, lithium or placebo for 18 months. Time until the next episode needed treating more than doubled on lamotrigine.
What was measured
Median time from randomisation to intervention for any mood episode over 18 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two prospectively harmonised 18-month trials enrolled 1,315 patients with bipolar I disorder in an open-label phase; 638 were stabilised and randomised to lamotrigine (n=280), lithium (n=167) or placebo (n=191). Median time from randomisation to intervention for any mood episode was 86 days on placebo (95% CI 58 to 121), 184 days on lithium (119 to not calculable) and 197 days on lamotrigine (144 to 388). Lamotrigine was superior to placebo for time to intervention for depression; lithium and lamotrigine were both superior for mania, but after adjustment for index mood only lithium remained superior for mania. Lithium produced more diarrhoea (19% against 7%) and tremor (15% against 4%). Neither drug caused affective switch.
Written into the record, not signed off as a reviewed claim
For acute bipolar depression the effect is confined to the severely depressed
In plain words
Lamotrigine is often described as an antidepressant for bipolar disorder. Pooling the raw data from all five trials shows the benefit is real only in people who were severely depressed at the start, and absent in everyone else.
What was measured
That lamotrigine treats bipolar depressive episodes generally, when the pooled individual-patient data localise the effect to the severe end and the licence covers maintenance only
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
An independent meta-analysis of individual patient data from 1,072 participants across five randomised placebo-controlled trials found more responders on lamotrigine on both the Hamilton scale (RR 1.27, 95% CI 1.09 to 1.47, p=0.002) and the Montgomery-Asberg scale (RR 1.22, 1.06 to 1.41, p=0.005). A significant interaction by baseline severity (p=0.04) showed superiority confined to participants with a Hamilton score above 24 (RR 1.47, 1.16 to 1.87, p=0.001), with no separation from placebo at scores of 24 or below (RR 1.07, 0.90 to 1.27, p=0.445). The United States approval is for maintenance treatment to delay mood episodes, not for treatment of an acute depressive episode.
Written into the record, not signed off as a reviewed claim
The pregnancy data are the best of any effective anti-seizure drug
In plain words
Across 2,514 pregnancies exposed to lamotrigine alone, the birth-defect rate was 2.9%, inside the range reported for unexposed pregnancies. Children exposed in the womb had a mean IQ of 108 at age 6.
What was measured
Major congenital malformation prevalence at 1 year, and adjusted IQ at 6 years, by drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the EURAP prospective registry covering 42 countries, major congenital malformation prevalence at one year was 74 of 2,514 (2.9%) for lamotrigine monotherapy, against 10.3% for valproate and 5.5% for carbamazepine; prevalence rose with dose at conception for lamotrigine (p=0.0145), and the reference category throughout was lamotrigine at 325 mg/day or less. In the separate NEAD prospective study, adjusted IQ at 6 years was 108 (95% CI 105 to 110) after lamotrigine exposure against 97 (94 to 101) after valproate (p=0.0003). Both are observational: drug choice was not randomised, and the lamotrigine group differed from the valproate group in seizure type as well as in treatment.
Written into the record, not signed off as a reviewed claim
How many documents were read
102 documents were read for this substance.
RNAWiki source record
99 of them state the same halfLife, and they agree.
RNAWiki source record
16 of them state the same tMax, and they agree.
RNAWiki source record
102 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
U3H27498KS
CAS registry number
84057-84-1
PubChem compound
3878
RxNorm concept
28439
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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.
Withdrawn in United States, 2019, for "Cross Contamination; Lamotrigine Tablets 100 mg USP was contaminated with enalapril maleate." (openFDA drug enforcement Class I recall)
What the approval register records
61 approved applications cover products containing this substance. The earliest was NDA020241, approved 19941227 to GLAXOSMITHKLINE LLC.
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What is not here
7 questions this page could not answer
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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 sodium-channel blocker that beat carbamazepine on time to treatment failure in 1,721 patients in SANAD and beat both levetiracetam and zonisamide on per-protocol 12-month remission in SANAD II, at the cost of a boxed warning for serious rash occurring in about 3 adults and 8 children per 1,000.
Recorded evidence blocks (10)
Q2
On the Lamotrigine label: indicated for what?
"Lamotrigine extended-release tablets are indicated for: adjunctive therapy for primary generalized tonic-clonic seizures (PGTC) and partial-onset seizures with or without secondary generalization in patients aged 13 years and older. (1.1) conversion to monotherapy in patients aged 13 years and older with partial-onset…": indications and usage on Lamotrigine's label. DailyMed label · 0833d3df-2df1-4abd-abe0-7fb2c0253c80 · 2026-08-13
Q3
163 registered trials of Lamotrigine — at which phases?
Registered studies posting no result
111 of 163
163 registered studies of Lamotrigine: 42 phase1, 40 phase3, 32 phase4, 21 phase2, 16 na or unstated, 15 na. CLINICALTRIALS_SNAPSHOT · 2026-09-01
555 with a PubMed record
Show the evidence
phase1
42
phase3
40
phase4
32
phase2
21
na or unstated
16
na
15
6 more recorded rows
completed
129
unknown
14
terminated
12
recruiting
5
withdrawn
2
available
1
recorded 2026-09-01 · last checked 2026-09-04
Q4
8 of Lamotrigine's trials stopped: accrual/recruitment, funding/business, other?
terminated; "Slow recruitment; trial unlikely to reach completion"
NCT01674010
terminated; "Business Decision"
NCT01891890
terminated; "Poor recruitment"
NCT02256124
terminated; "Due to our experience, the small number of new inclusions, and the uncertainty regarding the COVID-19 outbreak, we have decided to discontinue the study."
NCT02389712
terminated; "Difficulties with recruitment"
2 further recorded trials
NCT02893371
terminated; "Per PI, this study is not a clinical trial and was inadvertently entered in the system"
NCT03504501
terminated; "The study has been terminated prematurely due to recruitment difficulties. Current status: recruitment stopped and cleaning of the database is ongoing."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Lamotrigine used lamotrigine, 300 mg/day — over how long?
studies of Lamotrigine used the recorded amount. ClinicalTrials.gov · 2026-09-01
17 recorded entries; human; tablet, oral; also "lamotrigine, 300 mg/day", "lamotrigine, 250 mg/day", "Lamotrigine Tablets 25 mg"
Show the evidence
human
NCT00355082
lamotrigine, 300 mg/day
NCT00355082
lamotrigine, 250 mg/day
NCT00647751
Lamotrigine Tablets 25 mg
NCT00647751
Lamictal® Tablets 25 mg
NCT01513681
Lamictal® 200 mg
NCT01879423
Lamotrigine Dispersible/Chewable tablets 5mg*5
11 more recorded rows
humanNCT01879423
tablet; Lamotrigine Compressed tablet 25mg
humanNCT03419949
oral; oral lamotrigine 100 mg
humanNCT03831854
Lamotrigine 300 MG
humanNCT03831854
Lamictal 300 mg
humanNCT04938856
Test Group (Lamnet 100 mg), Reference Group (Lamictal 100 mg)
humanNCT04939675
LamoTRIgine 50mg
humanNCT04939675
Lamictal 50mg
humanNCT05017155
Lamotrigine 25Mg Oral Tablet, Extended Release
humanNCT05145608
tablet; Lamotrigine ER tablet 50mg
humanNCT05145608
tablet; Reference- Lamictal® XRTM (Lamotrigine) ER tablet 50mg
humanNCT06199791
Lamotrigine 100 MG
recorded 2026-09-01 · last checked 2026-09-04
Q6
Lamotrigine's half-life is 42.9 hours — which schedules were studied?
42.9 hours, the half-life Lamotrigine's label states: "The mean plasma half-lives determined in the study were 42.9 hours (chronic renal failure), 13.0 hours (during hemodialysis) and 57.4 hours (between hemodialysis) compared with 26.2 hours in healthy volunteers." DailyMed label · 0833d3df-2df1-4abd-abe0-7fb2c0253c80 · 2026-08-13
tmax 4 to 6 hours; bioavailability 21 %.
Show the evidence
half lifepharmacokinetics
42.9 hours; The mean plasma half-lives determined in the study were 42.9 hours (chronic renal failure), 13.0 hours (during hemodialysis) and 57.4 hours (between hemodialysis) compared with 26.2 hours in healthy volunteers.
tmaxpharmacokinetics
4 to 6 hours; In this study, the median time to peak concentration (T max ) following administration of lamotrigine extended-release was 4 to 6 hours in subjects taking carbamazepine, phenytoin, phenobarbital, or primidone;
bioavailabilitypharmacokinetics
21 %; The relative bioavailability of extended-release lamotrigine was approximately 21% lower than immediate-release lamotrigine in subjects receiving enzyme-inducing AEDs.
metabolismpharmacokinetics
Absorption Lamotrigine is absorbed after oral administration with negligible first-pass metabolism.
recorded 2026-08-13 · last checked 2026-09-04
Q7
Which 79 trials of Lamotrigine posted no result?
Posted no result
79 of 79 completed trials
Registrations
NCT00015106, NCT00001482, NCT01513681, NCT01513720, NCT00043914 and NCT00007670, and 73 more
Completion dates
oldest 1999-02; newest 2024-04-16
Show the evidence
Trial
NCT00015106
1999-02
NCT00001482
2001-05
NCT01513681
2002-11
NCT01513720
2002-12
NCT00043914
2003-01-29
NCT00007670
2003-03
14 further recorded trials
NCT01131949
2003-03
NCT01131975
2003-03
NCT00153244
2003-05
NCT00043875
2003-11
NCT00177567
2004-01
NCT00067938
2004-08
NCT00647751
2004-08
NCT00650208
2004-08
NCT00071747
2005-01
NCT00485771
2005-01
NCT00043901
2005-03-01
NCT00086593
2005-07
NCT00274677
2005-08
NCT00012558
2005-09
Q8
At the median, Lamotrigine's trials enrolled 58.5 people — anything larger?
Median enrolment
58.5
Largest enrolment
1037352
Registered trials counted
160
Q9
What do 10698 spontaneous reports say about Lamotrigine — 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.
Lamotrigine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 10698 reaction mentions were counted: rash 1895; pyrexia 1481; drug interaction 1057; drug reaction with eosinophilia and systemic symptoms 1019. FAERS via Open Targets · CHEMBL741 · 2026-06-24
Show the evidence
rash
1895
pyrexia
1481
drug interaction
1057
drug reaction with eosinophilia and systemic symptoms
1019
toxicity to various agents
977
stevens-johnson syndrome
970
4 more recorded rows
seizure
925
convulsion
896
somnolence
792
suicide attempt
686
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Lamotrigine's label not list?
convulsion, drug interaction and drug reaction with eosinophilia and systemic symptoms and 7 more reported for Lamotrigine, absent from its label. FAERS via Open Targets · CHEMBL741 · 2026-06-24
2 label terms; 10 reported and unlisted; 0833d3df-2df1-4abd-abe0-7fb2c0253c80
Show the evidence
convulsion
count not stated
drug interaction
count not stated
drug reaction with eosinophilia and systemic symptoms
count not stated
pyrexia
count not stated
rash
count not stated
seizure
count not stated
4 more recorded rows
somnolence
count not stated
stevens-johnson syndrome
count not stated
suicide attempt
count not stated
toxicity to various agents
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Q11
Lamotrigine and OCT2, CYP2D6 and TRANSPORTER: shared by which compounds?
Strong or moderate inducers of the cytochrome P450 3A4 (CYP3A4) enzyme, which are also known to induce UGT, may also enhance the metabolism of lamotrigine.
drug_interactions
Effect of Lamotrigine Extended-Release on Organic Cationic Transporter 2 Substrates Lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins [see Clinical Pharmacology (12.3) ] .
drug_interactions
Co-administration of lamotrigine extended-release with OCT2 substrates with a narrow therapeutic index (e.g., dofetilide) is not recommended.
drug_interactions
(7, 12.3) Co-administration with organic cationic transporter 2 (OCT2) substrates with narrow therapeutic index is not recommended.
pharmacokinetics
Other In vitro assessment of the inhibitory effect of lamotrigine at OCT2 demonstrate that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of OCT2 at potentially clinically relevant concentrations, with IC 50 value of 53.8 μM [see Drug Interactions (7) ] .
pharmacokinetics
Results of in vitro experiments suggest that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6.
2 more recorded rows
Interaction statementclinical_pharmacology
Other In vitro assessment of the inhibitory effect of lamotrigine at OCT2 demonstrate that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of OCT2 at potentially clinically relevant concentrations, with IC 50 value of 53.8 μM [see Drug Interactions (7) ] .
Interaction statementclinical_pharmacology
Results of in vitro experiments suggest that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6.
Withdrawn in United States, 2019, for "Cross Contamination; Lamotrigine Tablets 100 mg USP was contaminated with enalapril maleate." (openFDA drug enforcement Class I recall)
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 · openFDA enforcement — 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: 7 source rows
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