Medication approval journey

lamotrigine (Lamictal)

Approved for Maintenance treatment of bipolar I disorder, to delay time to occurrence of mood episodes

page first published · last updated

Also answers to “the slow simmer” — its codename in our videos and posts. The full codebook

FDA approvedMood stabiliserTaper risk: high

How this page reads

The page as written, with the clinical terms

Plain language uses the same facts, the same numbers and the same caveats. It does not leave anything out. Quotes from the FDA label are never reworded in either setting.

Before you stop or change your lamotrigine dose

Stopping abruptly can be dangerous — never do it without medical supervision

Do not stop abruptly. Stopping lithium suddenly is associated with rebound mania and increased suicide risk. Several drugs in this group are also anticonvulsants, and stopping them abruptly can trigger seizures. Any change should be prescriber-supervised.

what the lamotrigine warnings mean

label facts below are read from the lamictal (lamotrigine) FDA label on DailyMed, set id d7e3572d-56fe-4727-2bb4-013ccca22678, version 45, effective october 10, 2025. the section numbers in brackets are the label’s own. every source is linked at the end of this section. last checked 2026-10-05.

lamotrigine was approved for epilepsy in 1994 and for the maintenance treatment of bipolar i disorder in june 2003, and about 2.5 million americans filled a prescription for it in 2024 [meps]. its label carries one boxed warning, about serious rash, and thirteen further numbered warnings, two of which were added long after approval. this section says what each means in plain words, why the dose has to be built up over six weeks, what the approval trials measured and for how long, which side effects the label counts and how often, and what independent research has found since, in both directions. every number is from the label, an fda safety communication, or a study in the library, and each source is linked at the end.

the legal and safety record for this drug has its own page on this site and is not repeated here [legal-record]. this is information to take to a prescriber. nothing here is a reason to start, stop or change a dose on your own; with this drug in particular, both starting too fast and stopping abruptly carry their own warnings.

the boxed warning: serious skin rashes, including stevens-johnson syndrome

the boxed warning says lamotrigine can cause serious rashes requiring hospitalization and stopping the drug, including stevens-johnson syndrome and toxic epidermal necrolysis, and that rash-related deaths have occurred. the label’s rate is approximately 0.3% to 0.8% in children aged 2 to 17 and 0.08% to 0.3% in adults [label, boxed warning and 5.1]. one rash-related death occurred in a prospectively followed group of 1,983 children with epilepsy. in adults, the rate in the bipolar and mood-disorder trials was lower than in the epilepsy trials: 0.08% (1 of 1,233) on lamotrigine alone and 0.13% (2 of 1,538) with other drugs, with no deaths among them [label 5.1].

the label names four things that raise the risk: taking valproate at the same time, starting at more than the recommended dose, raising the dose faster than recommended, and carrying the hla-b*1502 gene variant, which is found mainly in people of han chinese and thai ancestry and is linked to a roughly 2 to 3 times higher risk [label, boxed warning and 5.1]. it adds that cases have occurred with none of these. the valproate number is specific: in the epilepsy trials, 6 of 584 people (1%) taking both drugs were hospitalized for rash against 4 of 2,398 (0.16%) on lamotrigine without valproate [label 5.1].

timing is the practical part. nearly all life-threatening rashes occurred within 2 to 8 weeks of starting, though isolated cases have appeared after 6 months, so the label says time on the drug cannot be relied on as reassurance. benign rashes happen too, and the label says it is not possible to tell which rashes will turn serious, so lamotrigine "should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related", and stopping may not prevent a rash from becoming life-threatening or disfiguring [label, boxed warning]. across 122 randomised trials and 18,698 people, 8.3% developed some skin reaction and 8 people (0.04%, about 1 in 2,300) developed stevens-johnson syndrome or toxic epidermal necrolysis [bloom-2017].

the slow start: why the dose is built up over six weeks

the dose schedule is itself a safety measure, and it changes with what else a person takes [label 2.1, 2.4, table 5]. for an adult with bipolar disorder taking neither valproate nor an enzyme-inducing drug: 25 mg a day for weeks 1 and 2, 50 mg for weeks 3 and 4, 100 mg in week 5, and 200 mg from week 6, which is the target. with valproate the schedule is halved and slowed: 25 mg every other day for weeks 1 and 2, 25 mg a day for weeks 3 and 4, 50 mg in week 5, and 100 mg from week 6, with 100 mg the target, because "the dosage of lamotrigine in the presence of valproate is less than half of that required in its absence" [label 5.12]. with carbamazepine, phenytoin, phenobarbital or primidone and no valproate, it runs faster and higher: 50 mg, then 100, 200, 300 and up to 400 mg by week 7 [label table 5].

the target is 200 mg a day. the trials tested up to 400 mg and found no added benefit over 200 mg, so the label says doses above 200 mg are not recommended [label 2.4]. starter kits exist to deliver the first five weeks in the right steps [label 2.1]. two rules follow from the half-life, which is about 25 hours on its own and about 70 hours with valproate [label 12.3, table 14]: if lamotrigine has been missed for more than five half-lives, the label says to go back to the starting dose and build up again rather than resume the old dose; and if valproate is stopped, the lamotrigine dose is doubled over two weeks, while if an enzyme inducer is stopped it is halved over two weeks [label 2.1, 2.4, table 6].

stopping also has a schedule. the label says lamotrigine should not be stopped abruptly, that two adults in the bipolar trials had seizures shortly after abrupt withdrawal, and that unless safety requires faster, the dose should be tapered over at least two weeks at roughly 50% a week [label 5.10, 2.1].

the other warnings, in plain words

the warnings section runs from 5.1 to 5.14. two of them did not exist when the drug was approved for bipolar disorder.

  • hemophagocytic lymphohistiocytosis, hlh [5.2]: a life-threatening syndrome of runaway immune activation, with fever, enlarged liver or spleen, rash, swollen lymph nodes, neurological symptoms, low blood counts and abnormal liver and clotting tests, reported 8 to 24 days after starting. the label says to evaluate at once and stop lamotrigine if no other cause is found. the fda added this subsection in june 2018, fifteen years after the bipolar approval, from post-marketing reports, so no rate can be given [fda-2018].
  • multiorgan hypersensitivity, dress [5.3]: fever, rash and swollen lymph nodes with organ involvement (liver, kidney, blood, heart or muscle). in the epilepsy trials, 2 of 3,796 adults and 4 of 2,435 children died of acute multiorgan or liver failure. the label says early signs such as fever and swollen glands can appear before any rash.
  • heart rhythm [5.4]: in laboratory testing lamotrigine behaves like a class ib antiarrhythmic at ordinary blood levels, so the label says it could slow conduction and provoke an arrhythmia, which can lead to sudden death, in people with structural or functional heart disease: heart failure, valve or congenital disease, conduction disease, ventricular arrhythmias, channelopathies such as brugada, significant ischemic disease, or several risk factors for coronary disease. the fda announced this in march 2021 on the basis of in vitro findings, not an outcome trial [fda-2021]. a 2025 nih-funded claims study of 367,445 people then counted outcomes: in bipolar disorder, ventricular tachycardia in 0.79% a year on lamotrigine against 0.68% on alternatives, a hazard ratio of 1.33, which is about one extra case per 900 people a year; the signal did not reach significance in the two epilepsy groups [radwanski-2025].
  • blood disorders [5.5]: low neutrophils, white cells, red cells or platelets, rarely aplastic anemia, with or without a hypersensitivity syndrome.
  • suicidal thoughts and behavior [5.6]: a class warning on all antiepileptic drugs. across 199 placebo-controlled trials of 11 such drugs, 0.43% of 27,863 people on drug against 0.24% of 16,029 on placebo had suicidal thoughts or behavior, a relative risk of 1.8 and roughly 1 additional person per 530 treated; for psychiatric indications the label gives 8.5 against 5.7 per 1,000. there were 4 suicides on drug and none on placebo, too few to draw a conclusion. the risk appeared as early as one week in and was consistent across drugs and ages.
  • aseptic meningitis [5.7]: headache, fever, stiff neck, nausea and vomiting, reported from 1 day to about six weeks after starting, resolving on stopping and returning fast and worse on re-exposure.
  • name confusion [5.8]: lamictal and lamotrigine have been mixed up with other drugs at the pharmacy, and the formulations with each other; the label tells people to look at their tablets each time they fill the prescription.
  • estrogen contraceptives [5.9]: the combined pill lowers lamotrigine levels by about 50%, and in the pill-free week the level can rise by as much as double, bringing dizziness, unsteadiness and double vision [label 7, table 13]. the label says dose adjustments "will be necessary in most patients" who start or stop an estrogen contraceptive, and that progestin-only methods do not have this effect [label 2.1]. the measurement behind it: 13 micromoles per litre in 22 women on the combined pill against 28 in 30 women not taking it, for the same dose [sabers-2003].
  • withdrawal seizures [5.10]: see the stopping schedule above.
  • the valproate combination [5.12]: valproate roughly doubles lamotrigine levels and more than doubles the rash risk, so the dose is less than half [label 7, 5.1]; carbamazepine, phenytoin, phenobarbital, primidone and rifampin cut levels by about 40% [label table 13]. the extended-release label sets out the same two interactions in the same words [xr-label].
  • melanin binding [5.13]: lamotrigine binds to melanin and could accumulate in the eye over years; the label says the testing done was inadequate to rule out long-term effects and gives no monitoring recommendation.
  • false-positive drug screens [5.14]: lamotrigine can trigger a positive result for pcp on some rapid urine tests; a confirmatory test sorts it out.

what the approval trials measured, and for how long

the bipolar approval is for maintenance only: delaying the next mood episode in people already treated for an acute episode. the label states that effectiveness in treating an acute manic, mixed or depressive episode "has not been established" and that use for acute mania is not recommended [label 1.2]. the evidence is two placebo-controlled trials in adults aged 18 to 82: trial 1 enrolled 404 people with a recent depressive episode and trial 2 enrolled 171 with a recent manic or hypomanic episode; 28% to 30% had rapid cycling [label 14.2].

both used a randomised-withdrawal design. everyone first took lamotrigine openly for 8 to 16 weeks, built up to 200 mg while other drugs were withdrawn (81% of the 1,305 people in this phase were on another psychotropic), and only those who stayed stable for at least four weeks were randomised to lamotrigine or placebo for up to 18 months. the endpoint was time to any intervention for a mood episode. in trial 1, 50 mg (50 people), 200 mg (124) and 400 mg (47) were compared with placebo (121); 200 and 400 mg combined beat placebo and 400 mg added nothing over 200. in trial 2, 100 to 400 mg (59 people, mean 211 mg) beat placebo (70) [label 14.2]. a combined analysis found a significant delay of both depression and mania, "more robust for depression" [label 14.2]. the label gives no relapse percentages. a design that randomises only the people who tolerated and responded to the drug measures how well it holds, not how often it works in the first place.

in children and adolescents the same design failed: a randomised-withdrawal trial in 301 patients aged 10 to 17 did not establish safety or efficacy for bipolar maintenance, and suicidal ideation was reported in 5% on lamotrigine against 0% on placebo [label 8.4].

side effects, with the label’s numbers

in the monotherapy phase of the two 18-month trials (227 on lamotrigine, 190 on placebo), the label’s table 12 lists what occurred in at least 5% and more often than placebo: nausea 14% against 11%, insomnia 10% against 6%, sleepiness 9% against 7%, back pain 8% against 6%, fatigue 8% against 5%, non-serious rash 7% against 5%, rhinitis 7% against 4%, abdominal pain 6% against 3%, dry mouth 6% against 4%, constipation 5% against 2%, vomiting 5% against 2% [label 6.1, table 12]. dizziness, mania, headache and diarrhea occurred at least as often on placebo. weight gain is listed among reactions in 1% to 5% [label 6.1].

during the dose-escalation phase, when people were also on other drugs, headache (25%), rash (11%) and dizziness (10%) were the most common [label 6.1]. in the 18-month trials, 13% on lamotrigine left because of a side effect against 16% on placebo and 23% on lithium; rash (3%) and mania or hypomania (2%) were the usual reasons [label 6.1]. manic, hypomanic or mixed episodes reported as adverse reactions ran 5% on lamotrigine, 4% on lithium and 7% on placebo over 18 months [label 6.1].

what the research says, in both directions

in favour. a 2021 cochrane review of 11 trials and 2,314 people found lamotrigine lowered the chance of a mood recurrence against placebo (risk ratio 0.67 for manic recurrence) and caused fewer side effects than lithium [cochrane-2021]. in a 2014 network meta-analysis of 33 maintenance trials and 6,846 patients it prevented relapse better than placebo and was among the best-tolerated options [miura-2014]. the pooled 18-month trials put the median time to the next episode at 197 days on lamotrigine against 86 on placebo, with the effect mainly against depressive relapse [goodwin-2004]. for acute bipolar depression, where the label claims nothing, an independent analysis of individual data from 1,072 patients in five trials found modestly more responders than placebo (risk ratio 1.27), larger in severe depression [geddes-2009].

against, or smaller than it sounds. the cochrane reviewers note that 8 of the 11 trials were funded by the manufacturer, and that manic episodes were about twice as likely on lamotrigine as on lithium [cochrane-2021]. the network meta-analysis concluded lithium should remain first-line because it prevents both manic and depressive relapse with better evidence [miura-2014]. all five acute-depression trials in the pooled analysis were run and funded by the manufacturer, and the pooled effect was modest [geddes-2009]. the maintenance trials randomised only people who had already tolerated and stabilised on the drug [label 14.2].

the warnings, measured. the rash rate across 122 trials is above [bloom-2017]. the 2021 heart warning rested on laboratory findings [fda-2021]; the 2025 cohort is the first count of what happened to people, and found a real but small absolute difference in bipolar disorder only [radwanski-2025]. the hlh warning has no rate, because it came from voluntary reports [fda-2018]. the contraceptive interaction was measured in 52 women with epilepsy, levels not relapses [sabers-2003].

questions to ask your prescriber about lamotrigine

each one comes from a warning or a study above. they are questions, not instructions; the answers depend on a history nobody here has.

  • the label says to stop at the first sign of rash unless it is clearly not the drug. in the first eight weeks, what does a rash that needs a same-day call look like, and who do i call?
  • am i on the valproate schedule, the standard schedule or the faster one, and does my starter kit match it?
  • if i miss several days, the label says to restart from the beginning rather than resume. how many days is that for me, given what else i take?
  • i take, or might start or stop, an estrogen-containing contraceptive. the label says the dose will need to change in most people. has a level been checked, and what is the plan around the pill-free week?
  • do i have a heart condition or risk factor that puts me in the group the 2021 warning was written about, and has anyone done an ecg?
  • what should i watch for in the first month that would point to hlh or a hypersensitivity reaction: fever, swollen glands, a rash together?
  • the approval is for preventing the next episode, not treating this one. what is treating the current episode, and how will we judge whether lamotrigine is doing its job?

questions people ask

what does the lamotrigine black box warning mean?
it says lamotrigine can cause serious rashes, including stevens-johnson syndrome and toxic epidermal necrolysis, that have required hospitalization and have caused deaths. the label puts the rate at about 0.3% to 0.8% in children and 0.08% to 0.3% in adults; in the adult bipolar trials it was 0.08% to 0.13%. the risk is higher with valproate, with a starting dose or escalation faster than recommended, and with the hla-b*1502 gene variant. nearly all serious rashes appear within 2 to 8 weeks, and the label says to stop at the first sign of any rash unless it is clearly not drug-related, because benign and serious rashes cannot be told apart early. across 122 trials, about 1 in 2,300 people developed stevens-johnson syndrome or toxic epidermal necrolysis.
why does lamotrigine have to be started so slowly, and what if i miss doses?
because starting high or raising the dose fast increases the rash risk. for an adult with bipolar disorder not on valproate or an enzyme inducer, the label’s schedule is 25 mg a day for two weeks, 50 mg for two weeks, 100 mg for a week, then 200 mg, the target. with valproate every step is halved and 100 mg is the target. the label says that after missing the drug for more than five half-lives, about five days on its own and longer with valproate, dosing should restart from the beginning rather than resume at the old dose. stopping, when it happens, is a taper of at least two weeks.
what are the most common lamotrigine side effects?
in the label’s two 18-month bipolar trials (227 on lamotrigine, 190 on placebo): nausea 14% vs 11%, insomnia 10% vs 6%, sleepiness 9% vs 7%, back pain 8% vs 6%, fatigue 8% vs 5%, non-serious rash 7% vs 5%, rhinitis 7% vs 4%, abdominal pain 6% vs 3%, dry mouth 6% vs 4%, constipation 5% vs 2%, vomiting 5% vs 2%. dizziness, headache and mania were no more common than on placebo. 13% on lamotrigine stopped for a side effect against 16% on placebo and 23% on lithium.
does birth control affect lamotrigine?
yes, if it contains estrogen. the combined pill lowers lamotrigine levels by about 50%, and in the pill-free week levels can rise to as much as double, which can cause dizziness, unsteadiness and double vision. the label says dose adjustments will be necessary in most people who start or stop an estrogen-containing contraceptive, and that progestin-only methods do not have this effect. in the study behind the warning, women on the combined pill had 13 micromoles per litre of lamotrigine against 28 in women not taking it, at the same dose. hormone replacement has not been studied but may act the same way.
does lamotrigine affect the heart?
the label warns that lamotrigine acts like a class ib antiarrhythmic in laboratory testing and could cause serious arrhythmias or sudden death in people with structural or functional heart disease, including heart failure, valve or congenital disease, conduction disease and brugada syndrome. the fda added the warning in 2021 from in vitro findings. a 2025 study of 367,445 people then found ventricular tachycardia in 0.79% a year on lamotrigine against 0.68% on alternatives in bipolar disorder, about one extra case per 900 people a year, with no significant difference in the epilepsy groups. the label says the warning is about people with heart disease, not everyone.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

  1. lamictal (lamotrigine) prescribing information, fda label on dailymed (set id d7e3572d-56fe-4727-2bb4-013ccca22678, version 45, effective october 10, 2025): boxed warning; sections 1.2, 2.1, 2.4 tables 5 and 6, 5.1 to 5.14, 6.1 table 12, 7 table 13, 8.4, 12.3 table 14, 14.2
  2. ahrq medical expenditure panel survey, prescribed medicines public-use file 2024 (hc-254a): people with at least one lamotrigine purchase, weighted; computed by veisund, method on the usage section of this page
  3. bloom r, amber kt. identifying the incidence of rash, stevens-johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials. anais brasileiros de dermatologia 2017 (library row)
  4. fda safety-related labeling change, 27 june 2018 (suppl-57): warnings and precautions 5.2, hemophagocytic lymphohistiocytosis, new subsection added to the lamictal label (library row)
  5. fda drug safety communication, 31 march 2021: studies show increased risk of heart rhythm problems with lamotrigine in patients with heart disease (library row)
  6. radwanski p, et al. association of ventricular arrhythmias with lamotrigine: an observational cohort study. scientific reports 2025 (library row)
  7. sabers a, et al. oral contraceptives reduce lamotrigine plasma levels. neurology 2003 (library row)
  8. hashimoto y, et al. lamotrigine in the maintenance treatment of bipolar disorder. cochrane database of systematic reviews 2021 (library row)
  9. miura t, et al. comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis. lancet psychiatry 2014 (library row)
  10. goodwin gm, et al. a pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar i disorder. journal of clinical psychiatry 2004 (library row)
  11. geddes jr, calabrese jr, goodwin gm. lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. british journal of psychiatry 2009 (library row)
  12. lamotrigine’s dose is less than half with valproate, and the level swings with estrogen contraceptives (lamictal xr prescribing information, sections 5.9, 5.12 and 7, read august 2026) (library row)

How long the lamotrigine trials actually ran

The longest trial behind the lamotrigine approval ran 78 weeks (about 18 months).

The gap between how long the trials ran and how long people actually take these medications is the single most important thing on this page. It is not evidence that longer use is unsafe or ineffective. It is evidence that longer use was not what got tested.

People often stay on these drugs for far longer than the trials ran. The trials behind the approval ran up to 18 months. That is longer than most on this site.

That does not mean longer use is unsafe. It does not mean the drug stops working either. It means longer use was never the thing that got tested.

If you have been on it a long time, that is a fair thing to ask your prescriber about.

Boxed warning: serious skin rashes

The strongest warning the FDA puts on a label, often called a black box warning. It is reproduced below word for word, not summarised.

This is the strongest warning the FDA can put on a drug label. Some people call it a black box warning. We copied it word for word. We did not shorten it and we did not soften it.

The warning below is about serious skin rashes. This drug can cause a rash bad enough to need hospital care. It can also mean stopping the drug. One of those rashes is a severe skin reaction called Stevens-Johnson syndrome. About 0.3 to 0.8 out of every 100 patients aged 2 to 17 get such a rash. In adults it is about 0.08 to 0.3 out of every 100. One rash death was reported in a followed group of 1,983 children with epilepsy. They were taking the drug as an add-on.

The FDA’s own words follow, copied exactly.

WARNING: SERIOUS SKIN RASHES LAMICTAL can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.3% to 0.8% in pediatric patients (aged 2 to 17 years) and 0.08% to 0.3% in adults receiving LAMICTAL. One rash-related death was reported in a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking LAMICTAL as adjunctive therapy. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate. In addition to age, factors that may increase the risk of occurrence or the severity of rash caused by LAMICTAL include (1) coadministration of LAMICTAL with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of LAMICTAL, (3) exceeding the recommended dose escalation for LAMICTAL, or (4) the presence of the HLA-B*1502 allele. However, cases have occurred in the absence of these factors. Nearly all cases of life-threatening rashes caused by LAMICTAL have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash. Although benign rashes are also caused by LAMICTAL, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Accordingly, LAMICTAL should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related. Discontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring [see Warnings and Precautions ( 5.1 )] . WARNING: SERIOUS SKIN RASHES See full prescribing information for complete boxed warning. • Cases of life-threatening serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and/or rash-related death have been caused by lamotrigine. The rate of serious rash is greater in pediatric patients than in adults. Additional factors that may increase the risk of rash include: o coadministration with valproate. o exceeding recommended initial dose of LAMICTAL. o exceeding recommended dose escalation for LAMICTAL. o presence of the HLA-B*1502 allele. ( 5.1 ) • Benign rashes are also caused by lamotrigine; however, it is not possible to predict which rashes will prove to be serious or life threatening. LAMICTAL should be discontinued at the first sign of rash, unless the rash is clearly not drug related. ( 5.1 )

FDA label effective October 10, 2025 — read the full label on DailyMed

What lamotrigine is FDA approved for, and the trials behind it

Approved for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy; the epilepsy indications came first, in 1994 in 2003, under application NDA 020241 SUPPL-17. Source: FDA Drugs@FDA.

The bipolar-maintenance approval rests on 2 multicenter, double-blind, placebo-controlled trials in adults aged 18 to 82 with bipolar I disorder — one enrolling 404 patients with a recent depressive episode, the other 171 patients with a recent manic or hypomanic episode. After an 8- to 16-week open-label period on lamotrigine, stabilized patients were randomized to lamotrigine monotherapy or placebo for up to 18 months. In the first trial patients received 50, 200, or 400 mg/day (n = 50, 124, and 47) against placebo (n = 121); in the second, 100 to 400 mg/day (n = 59) against placebo (n = 70). Lamotrigine was superior to placebo on time to intervention for a mood episode in both.

The FDA approved lamotrigine in 2003. The approved use was long-term treatment of bipolar I disorder. The goal is to push back the return of mood episodes. It is for people already treated for a mood episode. The epilepsy uses came first, in 1994. The file number is NDA 020241 SUPPL-17. The source is Drugs@FDA, the FDA's own database.

Two trials backed this use. They ran at several sites against a placebo. Nobody knew who got the drug (multicenter, double-blind).

Patients were adults aged 18 to 82 with bipolar I disorder. One trial held 404 people who had just had a depressive episode. The other held 171 who had just had a manic or hypomanic one.

Everyone first took the drug openly for 8 to 16 weeks. Those who became stable were then split by chance. Some stayed on the drug alone. Some moved to a placebo. That ran for up to 18 months.

In the first trial, people got 50, 200, or 400 mg a day. Those groups held 50, 124, and 47 people, against a placebo in 121. In the second, they got 100 to 400 mg a day, 59 people against a placebo in 70.

In both trials the drug beat the placebo on one measure. That was how long people went before they needed help for a mood episode.

Trials
2 placebo-controlled trials
Duration
Up to 18 months
Participants
404 and 171 patients in the 2 trials
Compared against
Placebo
The effectiveness of LAMICTAL in the maintenance treatment of bipolar I disorder was established in 2 multicenter, double-blind, placebo-controlled trials in adult patients (aged 18 to 82 years) who met DSM-IV criteria for bipolar I disorder.

Verbatim from the lamotrigine FDA label, Clinical Studies section, effective October 10, 2025 — read the full label on DailyMed.

Side effects of lamotrigine in the approval trials

Incidence among 227 patients on lamotrigine monotherapy (100 to 400 mg/day) versus 190 on placebo in the 2 placebo-controlled bipolar I trials of 18 months' duration. The label cautions that rates from a drug's clinical trials cannot be directly compared with rates from another drug's trials and may not reflect the rates observed in practice.

Read the limits first. These numbers come from the two bipolar I trials against a placebo. Those ran 18 months. 227 people took the drug on its own at 100 to 400 mg a day. 190 took a placebo.

The label warns that you cannot line these rates up against another drug’s trials. It warns that real life may not match them either.

  • Nausea (14% vs 11% on placebo)
  • Insomnia (10% vs 6%)
  • Somnolence (9% vs 7%)
  • Back pain (8% vs 6%)
  • Fatigue (8% vs 5%)
  • Rhinitis (7% vs 4%)
  • Rash, nonserious (7% vs 5%)
  • Abdominal pain (6% vs 3%)
  • Dry mouth (6% vs 4%)
  • Constipation (5% vs 2%)
  • Vomiting (5% vs 2%)
Bipolar disorder: Most common adverse reactions (incidence >5%) in adults were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia.

From the lamotrigine FDA label, Adverse Reactions section, effective October 10, 2025 — DailyMed.

More from the lamotrigine label: warnings and precautions

  • Do not stop abruptly

    The label advises against abrupt discontinuation: unless safety concerns require a more rapid withdrawal, the dose should be tapered over a period of at least 2 weeks, at approximately 50% reduction per week. In the clinical development program in adults with bipolar disorder, 2 patients experienced seizures shortly after abrupt withdrawal.

    FDA label, Warnings and Precautions section.

  • No withdrawal syndrome seen in the bipolar trials

    In the 2 controlled bipolar trials, the label reports no increase in the incidence, severity, or type of adverse reactions after abruptly terminating lamotrigine.

    FDA label, Adverse Reactions section.

How many Americans take lamotrigine

Survey-based federal estimates, published with a lag of about two years. They count prescriptions filled, not outcomes.

These are federal survey numbers. They come out about two years late. They count prescriptions filled. They do not tell you if the drug helped.

12,624,285
prescriptions in the United States (2024), refills included
2,474,525
people filling them (2024), ± 492,085 (95%)

From 2014 to 2024 the estimate moved down 1%, but that is within the survey’s margin of error, so we do not call it a rise or a fall. Whatever you decide about lamotrigine, you are deciding alongside about 2,474,525 other people in 2024.

Prescriptions by year: 2014 12,705,157 · 2015 12,096,328 · 2016 11,276,212 · 2017 12,053,691 · 2018 11,582,775 · 2019 10,690,318 · 2020 10,801,629 · 2021 13,244,443 · 2022 11,704,669 · 2023 10,895,179 · 2024 12,624,285.

Prescriptions are not clearly up or down since 2014. About 2.5 million people in the United States took it in 2024.

Correction (29 September 2026). An earlier version of this section took its numbers from ClinCalc DrugStats, a third-party site that republishes this survey; we now compute them from AHRQ’s public-use files ourselves. It said prescriptions were down 1% since 2014; that change is within the survey’s margin of error, so we no longer state a direction.

Source: AHRQ Medical Expenditure Panel Survey (MEPS), Prescribed Medicines public-use files, 2014 (HC-168A) through 2024 (HC-254A), computed by veisund. People with at least one purchase where the Multum generic name (RXDRGNAM) equals the drug, weighted by the year’s person weight; purchases include refills. Standard errors by Taylor linearization on VARSTR/VARPSU. AHRQ’s reliability rule: a year is not shown when fewer than 60 survey respondents reported the drug or the relative standard error is over 50%. AHRQ cautions that its 2018 questionnaire redesign and the 2020–2022 pandemic years make year-to-year comparisons less certain.

What people report to the FDA about lamotrigine

Read this before the numbers.

Anyone can file an adverse event report — patients, doctors, manufacturers — and nobody verifies that the drug caused what was reported. There is no denominator: tens of millions of prescriptions generate reports at an unknowable rate, and reporting rises with news coverage, not necessarily with harm. Counts below are report volumes, not rates, and cannot be compared between drugs. The FDA itself says not to use this data to make medical decisions — we show it because you deserve to see what is in the public record, with its limits stated plainly.

Read this before the numbers.

Anyone can send a report to the FDA. Patients can. Doctors can. Drug makers can. Nobody checks that the drug caused what the report describes.

There is also no bottom number. Tens of millions of prescriptions turn into reports at a rate nobody knows. Reports go up when a drug is in the news, and that is not the same as more harm.

So these are counts of reports. They are not rates. You cannot use them to compare one drug with another. The FDA itself says not to use this data to make medical choices.

We show it because it is on the public record, and you should get to see it with its limits named.

71,378
reports mentioning lamotrigine, all time
57,748
filed as serious (a report-level flag covering every drug and outcome in the report)
filed as serious. That flag covers the whole report, and one report can name more than one drug and more than one outcome.

Most-reported reactions

  • Drug ineffective6,211
  • Seizure4,309
  • Toxicity to various agents3,928
  • Off label use3,474
  • Drug interaction3,259
  • Completed suicide3,074
  • Fatigue3,000
  • Dizziness2,989
  • Nausea2,981
  • Rash2,884

“Drug ineffective” ranking this high is worth noticing: a report of not being helped counts as an adverse event too, and people file them in large numbers.

It is worth noticing how high “drug ineffective” ranks. A report that the drug did not help counts as an adverse event too. People file a lot of them.

Source: FDA Adverse Event Reporting System (FAERS), via openFDA, openFDA dataset refreshed 2026-07-30 (the refresh date of the query endpoint, not the date reports run through).

Drug interactions listed on the lamotrigine label

The FDA label’s interactions section, verbatim. A pharmacist checking your actual medication list beats any published list — including this one.

Below is the part of the FDA label that lists other drugs. It is copied word for word.

No list on the web can see what else you take. A pharmacist can. Ask one to check your full list.

Read the label’s interactions section

7 DRUG INTERACTIONS Significant drug interactions with LAMICTAL are summarized in this section. Uridine 5´-diphospho-glucuronyl transferases (UGT) have been identified as the enzymes responsible for metabolism of lamotrigine. Drugs that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine. 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. Those drugs that have been demonstrated to have a clinically significant impact on lamotrigine metabolism are outlined in Table 13 . Specific dosing guidance for these drugs is provided in the Dosage and Administration section, and, for women taking estrogen‑containing products, including oral contraceptives, in the Warnings and Precautions section [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.9 )] . Additional details of these drug interaction studies are provided in the Clinical Pharmacology section [see Clinical Pharmacology ( 12.3 )] . Table 13. Established and Other Potentially Significant Drug Interactions ↓ = Decreased (induces lamotrigine glucuronidation). ↑ = Increased (inhibits lamotrigine glucuronidation). ? = Conflicting data. Concomitant Drug Effect on Concentration of Lamotrigine or Concomitant Drug Clinical Comment Estrogen-containing oral contraceptive preparations containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel ↓ lamotrigine ↓ levonorgestrel Decreased lamotrigine concentrations approximately 50%. Decrease in levonorgestrel component by 19%. Carbamazepine and carbamazepine epoxide ↓ lamotrigine ? carbamazepine epoxide Addition of carbamazepine decreases lamotrigine concentration approximately 40%. May increase carbamazepine epoxide levels. Lopinavir/ritonavir ↓ lamotrigine Decreased lamotrigine concentration approximately 50%. Atazanavir/ritonavir ↓ lamotrigine Decreased lamotrigine AUC approximately 32%. Phenobarbital/primidone ↓ lamotrigine Decreased lamotrigine concentration approximately 40%. Phenytoin ↓ lamotrigine Decreased lamotrigine concentration approximately 40%. Rifampin ↓ lamotrigine Decreased lamotrigine AUC approximately 40%. Valproate ↑ lamotrigine ? valproate Increased lamotrigine concentrations slightly more than 2-fold. There are conflicting study results regarding effect of lamotrigine on valproate concentrations: 1) a mean 25% decrease in valproate concentrations in healthy volunteers, 2) no change in valproate concentrations in controlled clinical trials in patients with epilepsy. Effect of LAMICTAL 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 )] . This may result in increased plasma levels of certain drugs that are substantially excreted via this route. Coadministration of LAMICTAL with OCT2 substrates with a narrow therapeutic index (e.g., dofetilide) is not recommended. • Valproate increases lamotrigine concentrations more than 2-fold. ( 7 , 12.3 ) • Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%. ( 7 , 12.3 ) • Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%. ( 7 , 12.3 ) • Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50% and 32%, respectively. ( 7 , 12.3 ) • Coadministration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended ( 7 , 12.3 )

FDA label for lamotrigine, effective October 10, 2025 — DailyMed.

Label history: when this label changes, it is recorded in What changed.

Who pays for lamotrigine

Two claims datasets and one survey, covering different populations with different instruments — they cannot be reconciled by arithmetic, and where their sum crowds the all-payer estimate, that is a finding about the estimates rather than a percentage.

Medicare Part D · claims · 2024Medicaid · claims floor · 2024All-payer · survey · 2024Commercially insured adults · not publishedChildren · no per-drug data
Medicare Part D
Read the under-65 group correctly before the numbers: Medicare before 65 means the disabled and dual-eligible population — among the sickest, highest-need people in the program — and reading their utilization as typical adult use would be a category error. The beneficiary total sums brand-level rows, so treat it as an upper bound on distinct people. 679,206 beneficiaries filled 4,395,266 claims in 2024 — 359,509 aged 65 and over, and 319,697 under 65.
Medicaid
At least 4,511,361 prescriptions in 2024 — a floor, because 193 of 1,409 national data rows are suppressed for privacy and contribute zero. Medicaid covers more children than any insurer in the country and publishes no age split — how much of this number is pediatric use is not knowable from public data.
All payers (survey estimate)
A survey estimate from 143 respondents, which we computed from AHRQ’s MEPS 2024 Prescribed Medicines file (people with at least one purchase, weighted; purchases include refills), puts the whole country at 12,624,285 purchases and 2,474,525 people in 2024. Subtracting the public programs from it would produce a number for everyone else — and we do not print that number, because subtracting a survey from claims counts manufactures precision that does not exist.
The population nobody counts
The commercially insured working-age adult — statistically, the likeliest person to be reading this page — is the one population with no public per-drug count anywhere. Private claims data exists and is sold, but nothing a patient can check is published. For children the record is thinner still: no public source counts pediatric use of lamotrigine specifically; the closest the public record comes is condition-level treatment rates for children, which we have traced for one condition in how childhood ADHD got counted.

Sources: Medicare Part D Prescribers — by Geography and Drug, data.cms.gov, National rows, data year 2024 (published with ~17-month lag). Medicaid State Drug Utilization Data 2024, data.medicaid.gov, national aggregate rows. Retrieved 2026-09-01.

Who has been paying for lamotrigine, 2019–2024

Medicare Part D

Claims, all ages — the one payer with a public per-drug series.

20192024

3,940,238 → 4,395,266 claims

Medicare under 65

Beneficiaries, not ordinary working-age adults: Medicare before 65 means the disabled and dual-eligible population. A gap is a suppressed split, not zero.

20192024

Not published for these years.

Medicaid

A floor each year — small-cell rows are suppressed federally and excluded from the sum.

20192024

3,817,527 → 4,511,361 prescriptions (floor)

Commercially insured adults

No public dataset publishes per-drug commercial claims for any year — the absence is the finding, and it is rendered, not interpolated. The population this library most wants to inform is the one with no public per-drug series, in any year — insurers and PBMs hold that data privately. What the federal surveys do measure — how many adults take these medications at all — is on the adult-usage page.

Sources: Medicare Part D Prescribers by Geography and Drug (data.cms.gov, national rows, per data year); Medicaid State Drug Utilization Data (data.medicaid.gov, national rows). Claims, fills and beneficiaries are different units — compare each series only with itself.

The lamotrigine approval, step by step

  1. Step 1

    What the approval was actually based on

    Which studies did the FDA rely on, how long did they run, and who was in them?

    The effectiveness of LAMICTAL in the maintenance treatment of bipolar I disorder was established in 2 multicenter, double-blind, placebo-controlled trials in adult patients (aged 18 to 82 years) who met DSM-IV criteria for bipolar I disorder... Patients with a CGI-severity score of 3 or less maintained for at least 4 continuous weeks, including at least the final week on monotherapy with LAMICTAL, were randomized to a placebo-controlled double-blind treatment period for up to 18 months.

    FDA-approved labelling, 14 CLINICAL STUDIES 14.2 Bipolar Disorder — read the label on DailyMed

    Our reading

    This is the strongest duration record in the directory and it deserves saying plainly: the randomised period ran up to eighteen months, not three to ten weeks, because the claim itself is about maintenance. But read the second sentence again. Everyone was put on lamotrigine first, for eight to sixteen weeks, and only those who had already responded and stayed well for four weeks were randomised — 1,305 people entered that run-in and 471 reached randomisation. So the trials answer "does it keep working for people it already works for?", not "will it work for me?". Two further things worth knowing: the label states effectiveness in acute episodes has not been established and acute mania is not recommended, so if you were started on it while acutely unwell you are outside the studied use; and lamotrigine had already been on the market for epilepsy since 1994, which is why its serious-rash boxed warning predates this indication rather than arriving after it.

  2. Step 2

    The approval

    When was it approved, under what application, and by whose review?

    Approved
    June 20, 2003
    Application
    NDA020241 SUPPL-17
    Review
    STANDARD
    Original sponsor
    GlaxoSmithKline
    Holds it now
    GlaxoSmithKline LLC
    Label submissions since
    50

    Source: openFDA Drugs@FDA, original application ORIG-1

  3. Step 3

    What was added after it was on the market

    Which warnings arrived only after millions of people were already taking it?

    • A new life-threatening warning was added to lamotrigine in 2018

      15 years after approval

      In June 2018 the FDA added a subsection to the lamotrigine label that had not existed before: hemophagocytic lymphohistiocytosis, or HLH. It is a syndrome of runaway immune activation, and the label calls it life-threatening, with high mortality if it is not recognised early and treated. Reported signs include fever, rash, an enlarged liver or spleen, swollen lymph nodes, neurological symptoms, low blood counts, and abnormal liver and clotting results. Symptoms have been reported 8 to 24 days after starting the medication.

      Two things about this are worth sitting with. It arrived in 2018, and lamotrigine was approved for bipolar maintenance in 2003 and has been marketed since 1994 — this was not in the approval package. It came from people taking the drug afterwards. And the label gives no rate for it. That is not sloppiness: reports like these arrive voluntarily from a population of unknown size, so a frequency cannot honestly be calculated. What the label does say is that it has occurred, in both children and adults, across the conditions lamotrigine is used for.

      This is not a reason to stop, and stopping lamotrigine abruptly carries its own risk. It is a reason to know what the first month should not look like.

      Worth asking

      What exactly should I watch for in the first three or four weeks, who do I call if I get a fever and a rash at the same time, and is there anything in my history that makes this more likely.

      LAMICTAL (lamotrigine) safety-related labeling change, 27 June 2018 (SUPPL-57): Warnings and Precautions 5.2, Hemophagocytic Lymphohistiocytosis — new subsection added — U.S. Food and Drug Administration (2018)

    • The 2021 lamotrigine heart warning applies to a specific group, not everyone

      18 years after approval

      On 31 March 2021 the FDA announced a potential increased risk of heart rhythm problems with lamotrigine in people who have heart disease. The FDA had required the manufacturer to run laboratory studies after receiving reports of abnormal ECG findings and, in some cases, chest pain, loss of consciousness and cardiac arrest. Those studies showed lamotrigine behaves like a Class IB antiarrhythmic drug at concentrations people actually reach — it blocks sodium channels in heart muscle.

      The qualifier in the label is the whole point. In a thorough QT study in healthy individuals, therapeutic doses did not slow ventricular conduction. The concern is a defined group: people with clinically important structural or functional heart disease — heart failure, valvular or congenital heart disease, conduction system disease, ventricular arrhythmias, channelopathies such as Brugada syndrome, significant ischaemic heart disease, or multiple risk factors for coronary artery disease. In those people the label says lamotrigine could widen the QRS and induce a proarrhythmia that can lead to sudden death. Taking other sodium channel blockers alongside it may add to that.

      So this is a warning built on in vitro findings and on who is plausibly vulnerable, not on an outcome trial. That cuts both ways. It is not evidence of harm in the general population, and it is not something to wave off if you have a heart condition. The label's instruction is to weigh the expected benefit against that risk for the individual patient.

      Worth asking

      Do I have a heart condition or risk factor that puts me in the group this is about, has anyone done an ECG since I started this, and does anything else I take block sodium channels.

      Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease — U.S. Food and Drug Administration (2021)

    • Lamotrigine's dose is less than half with valproate, and the level swings with estrogen contraceptives

      23 years after approval

      Lamotrigine is a common mood stabiliser for bipolar depression. Two of its interactions are with drugs a psychiatric patient is very likely to be taking: another mood stabiliser, and the pill.

      Significant findings

      LAMICTAL XR prescribing information (GlaxoSmithKline, August 2026), section 5.12: "Because valproate reduces the clearance of lamotrigine, the dosage of lamotrigine in the presence of valproate is less than half of that required in its absence". The boxed warning about serious rash names the same combination as a risk factor: "coadministration of LAMICTAL XR with valproate (includes valproic acid and divalproex sodium)" is listed among "factors that may increase the risk of occurrence or the severity of rash", along with exceeding the recommended starting dose or escalating too fast.

      Section 5.9 on contraceptives: "Some estrogen-containing oral contraceptives have been shown to decrease serum concentrations of lamotrigine. Dosage adjustments will be necessary in most patients who start or stop estrogen-containing oral contraceptives while taking LAMICTAL XR. During the week of inactive hormone preparation (pill-free week) of oral contraceptive therapy, plasma lamotrigine levels are expected to rise, as much as doubling at the end of the week. Adverse reactions consistent with elevated levels of lamotrigine, such as dizziness, ataxia, and diplopia, could occur. Other oral contraceptive and other estrogen-containing therapies (such as HRT) have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters."

      Section 7 gives the mechanism: lamotrigine is cleared by glucuronidation, so "Drugs that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine," and strong CYP3A4 inducers such as carbamazepine also speed it up.

      Worth asking

      The contraceptive interaction is the one people are least often told about, and it runs in both directions within a single month: lower levels on the active pills, higher in the pill-free week. If you take lamotrigine and start, stop or change a hormonal contraceptive, including for reasons unrelated to mood, ask whether the lamotrigine dose needs to change with it. The Sabers 2003 row in this wave is the study that measured the drop.

      LAMICTAL XR (lamotrigine) extended-release tablets: FDA-approved prescribing information, Boxed Warning, Warnings and Precautions 5.9 and 5.12, Drug Interactions 7 — GlaxoSmithKline LLC; US Food and Drug Administration (2026)

  4. Step 4

    What independent research has found since

    What has been learned by people who were not selling it?

  5. Step 5

    What still is not known

    Which questions you might reasonably have has nobody answered yet?

    • The enrichment design excludes everyone who did not tolerate or respond to lamotrigine in the run-in. What is the benefit for an unselected patient starting today?
    • Eighteen months is the longest evidence here, and maintenance is often lifelong. What happens in year five?
    • Around 30% of participants had rapid-cycling bipolar disorder, but the trials were not designed to answer whether it helps that group specifically.
    • The combined analysis found the benefit "more robust for depression" than for mania. For a drug prescribed as a mood stabiliser, which pole is it actually stabilising?

The lamotrigine legal and safety record

Settled and adjudicated matters only, from primary sources — including the litigation that was decided for the manufacturer, and the cases this drug is verifiably not part of.

Read the lamotrigine legal and safety record

Deciding about lamotrigine?

Open lamotrigine (Lamictal) in veisund

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