Lamotrigine

Antiepileptic with dual mechanism

ATC code: N03AX09

Brand names: Lamictal, Crisomet, Lamotrix

Updated 17 Jul 2026 · Methodology

Indications

Bipolar disorder maintenance

First line

First-line for maintenance therapy of bipolar disorder with depressive predominance per CANMAT 2018 and the Spanish SEP 2024. Not effective for mania. Starting dose 25 mg once daily for 2 weeks with slow titration to 200 mg daily – fast titration raises severe cutaneous reaction risk. Effect develops over 6–8 weeks.

Particularly in bipolar disorder with depressive episode predominance.

Sources

ICD-10: F31 · ICD-11: 6A60

Focal epilepsy

First line

First-line in focal epilepsy in adults and adolescents from 13 years ( NG217, 2022; SANAD II trial) alongside levetiracetam; in children 2–12 years it is used as add-on therapy. Starting dose 25 mg once daily for 2 weeks, titrated to 100–400 mg daily. Particularly suitable in women of reproductive age – the lowest teratogenic potential among classic antiepileptics (malformation risk 2.5% vs 6–10% with valproate).

Sources

ICD-10: G40.2 · ICD-11: 8A60

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Mood stabilization

Not recommended

Lamotrigine is an antiepileptic drug. It is prescribed for epilepsy and for maintenance treatment of bipolar I disorder ( 2018 and NG185 guidelines). For everyday mood stabilization, lamotrigine does not work: no clinical studies of such use exist. The main risk is severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), especially with rapid dose escalation or combination with valproate ( boxed warning). If lamotrigine was prescribed for mood stabilization, consider seeking a second opinion.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Stabilizes the inactivated state of voltage-gated sodium channels, reducing repetitive neuronal firing. Also suppresses glutamate release. Compared with carbamazepine and phenytoin, has a favorable cognitive profile – less sedation and no memory impairment. Metabolized by UGT1A4 glucuronidation. Used in focal and generalized epilepsy, and as a mood stabilizer in bipolar disorder with depressive predominance.

Safety

Boxed warning

FDA boxed warning: severe cutaneous reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis), especially with rapid titration and in the first 2–8 weeks. Any rash warrants immediate discontinuation.

Contraindications

Lamotrigine hypersensitivity
Age under 2 (most indications)
Severe hepatic impairment

Serious adverse effects

Stevens–Johnson syndrome and toxic epidermal necrolysis
DRESS syndrome
Hemophagocytic lymphohistiocytosis
Aseptic meningitis
Hepatotoxicity
Suicidal ideation

Common adverse effects

Rash (most often in the first 8 weeks)
Headache
Dizziness
Drowsiness
Diplopia
Nausea
Insomnia

Pregnancy: can you take Lamotrigine?

In pregnant epilepsy patients, lamotrigine is a preferred choice – lowest teratogenic potential among classic antiepileptics. In T2 and T3, levels drop 50–80% due to estrogen-induced metabolism – regular monitoring and dose adjustment needed.

Breastfeeding: can you take Lamotrigine?

Milk concentrations are high (about 30% of maternal plasma). Infant rash and sedation are possible – monitor activity, weight gain, and skin. If problems arise, switch to formula.

RID, infant dose via milk: 10.1%
Maternal peak time: 3 h
Peak milk concentration: 3 mg/L

Calculate RID Safe feeding window Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take 1–2 times daily, with or without food. Slow titration is critical – weeks 1–2: 25 mg once daily; weeks 3–4: 50 mg; then 50–100 mg increases every 1–2 weeks to target. Concurrent valproate doubles lamotrigine levels and rash risk – halve the titration rate. Estrogen-containing contraceptives drop lamotrigine levels by 50% – dose adjustment needed when starting or stopping them.

Common myths

Myth: «start lamotrigine at the standard dose.» Fact: rapid titration carries Stevens-Johnson syndrome and toxic epidermal necrolysis risk (1 in 1000 adults, 1 in 100 children). Any rash in the first 8 weeks warrants immediate discontinuation and medical review. Myth: «lamotrigine works as an antidepressant.» Fact: as a mood stabilizer it prevents bipolar depressive relapses but is not indicated for unipolar depression – the effect is weaker than with SSRIs.

Drug–drug interactions

4 pairs found. Sorted from critical to minor.

MajorCarbamazepineAntiepileptics. Carboxamide derivatives

Mechanism

Carbamazepine induces the liver glucuronidation enzymes that clear lamotrigine, so lamotrigine leaves the blood faster (lamotrigine SmPC). According to the US Food and Drug Administration () label, carbamazepine lowers lamotrigine concentrations by about 40%. The effect also runs the other way: when lamotrigine is started in a patient on carbamazepine, central nervous system adverse effects can occur, and the FDA label notes that carbamazepine epoxide, the active metabolite, may rise.

Symptoms

If the lamotrigine dose is not adapted to carbamazepine, lamotrigine levels stay low and seizures may return. The lamotrigine SmPC notes a weaker response to lamotrigine when it is combined with enzyme inducers. After lamotrigine is started on top of carbamazepine, dizziness, ataxia, double vision, blurred vision and nausea can occur. When carbamazepine is stopped and the lamotrigine dose is not reduced, lamotrigine levels rise.

Management

The labels do not ban the pair, but lamotrigine with carbamazepine follows a separate schedule for inducers, and neither the starting dose nor the rate of increase may be exceeded (lamotrigine SmPC). In epilepsy, adults and adolescents from 13 years without valproate: 50 mg/day in weeks 1 and 2, 100 mg/day in two doses in weeks 3 and 4, then increases of no more than 100 mg every 1–2 weeks to the usual maintenance dose of 200–400 mg/day (lamotrigine SmPC). If the patient also takes valproate, the lower-dose valproate schedule applies (lamotrigine SmPC). In bipolar disorder, when carbamazepine is added to a stable lamotrigine dose of 200 mg, the dose stays at 200 mg in week 1, then 300 mg in week 2 and 400 mg from week 3. When carbamazepine is stopped, the steps go back down: from 400 mg to 300 mg in week 2 and 200 mg from week 3 (lamotrigine SmPC). The US Food and Drug Administration () label asks for these schedules to be followed closely; there is no target lamotrigine blood level, and the dose is set by clinical response (lamotrigine FDA label). If dizziness, ataxia or double vision appear after lamotrigine is started, the carbamazepine dose is reduced (lamotrigine SmPC).

Sources

Pair details →Carbamazepine →

MajorPhenytoinAntiepileptic, hydantoin derivative (sodium channel blocker)

Mechanism

Phenytoin induces UGT1A4. Lamotrigine falls 50%.

Symptoms

Seizure breakthrough.

Management

Double lamotrigine dose.

Sources

Pair details →Phenytoin →

MajorRifampicinAntituberculous antibiotic

Mechanism

Rifampicin induces UGT1A4. Lamotrigine falls 40%.

Symptoms

Seizure breakthrough.

Management

Increase lamotrigine by 50-100%.

Sources

Pair details →Rifampicin →

MajorValproic acidAntiepileptics. Fatty acid derivatives

Mechanism

Valproate inhibits glucuronidation, the main elimination route of lamotrigine, and the lamotrigine half-life nearly doubles (lamotrigine and valproate SmPCs). According to the US Food and Drug Administration () label, lamotrigine concentrations rise slightly more than 2-fold with valproate. The risk of serious lamotrigine rash is higher with a high starting dose, with a fast dose increase and with concomitant valproate (lamotrigine SmPC).

Symptoms

Rash, usually within the first 8 weeks of lamotrigine; nearly all life-threatening cases occur within 2–8 weeks. Severe forms: Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) with fever, swollen lymph nodes, facial oedema and blood, liver and kidney involvement. Fever and swollen lymph nodes can appear before the rash. Children have a higher risk of serious rash than adults.

Management

The labels do not ban the pair, but with valproate lamotrigine follows a separate, lower-dose schedule, and neither the starting dose nor the rate of increase may be exceeded (lamotrigine SmPC). In epilepsy, adults and adolescents from 13 years: 25 mg every other day in weeks 1 and 2, 25 mg/day in weeks 3 and 4, then increases of no more than 25–50 mg every 1–2 weeks to the usual maintenance dose of 100–200 mg/day (lamotrigine SmPC). This schedule applies with valproate even if the patient takes other drugs; in children aged 2–12 the dose is calculated per kilogram of body weight from a separate table (lamotrigine SmPC). In bipolar disorder, when valproate is added to a stable lamotrigine dose, the lamotrigine dose is halved from the first week, for example from 200 to 100 mg/day; the maximum dose with valproate is 200 mg/day (lamotrigine SmPC). The US Food and Drug Administration () valproate label also requires a lower lamotrigine dose. At the first sign of rash, lamotrigine is stopped at once unless the rash is clearly unrelated to it (lamotrigine SmPC).

Sources

Pair details →Valproic acid →

Label mentions66 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorDofetilide
«DRUG INTERACTIONS: 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…»
FDA, section 7 · Open on DailyMed
Moderateanticonceptivos hormonalesclass named in the label
«Empeoramiento clínico y riesgo de suicidio: La administración de una combinación de etinilestradiol/levonorgestrel (30 µg/150 µg) aumenta hasta aproximadamente el doble el aclaramiento de lamotrigina…»
AEMPS, section 4.4 · Open on CIMA
ModerateCarbamazepine
«Interacciones de fármacos antiepilépticos: Se han notificado efectos adversos que afectan al sistema nervioso central, como mareo, ataxia, diplopía, visión borrosa y náuseas, en pacientes que toman…»
AEMPS, section 4.5 · Open on CIMA
ModerateEthinylestradiol
«Empeoramiento clínico y riesgo de suicidio: La administración de una combinación de etinilestradiol/levonorgestrel (30 µg/150 µg) aumenta hasta aproximadamente el doble el aclaramiento de lamotrigina…»
AEMPS, section 4.4 · Open on CIMA
ModerateLevonorgestrel
«Empeoramiento clínico y riesgo de suicidio: La administración de una combinación de etinilestradiol/levonorgestrel (30 µg/150 µg) aumenta hasta aproximadamente el doble el aclaramiento de lamotrigina…»
AEMPS, section 4.4 · Open on CIMA
ModeratePhenytoin
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Fenitoína»
AEMPS, section 4.5 · Open on CIMA
ModerateRifampicin
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Rifampicina»
AEMPS, section 4.5 · Open on CIMA
Amitriptyline
«Interacciones de lamotrigina con agentes psicoactivos: Los estudios in vitro indican que la formación del principal metabolito de lamotrigina, el 2-N-glucurónido, se vio mínimamente inhibida por la…»
AEMPS, section 4.5 · Open on CIMA
antiarrítmicosclass named in the label
«ECG tipo Brugada y otras anomalías en el ritmo y la conducción cardíacos: En pacientes tratados con lamotrigina, se ha notificado alteración arritmogénica del segmento ST y la onda T y de un patrón…»
AEMPS, section 4.4 · Open on CIMA
Aripiprazole
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Aripiprazol»
AEMPS, section 4.5 · Open on CIMA
Atazanavir
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Atazanavir/ritonavir*»
AEMPS, section 4.5 · Open on CIMA
Atazanavir
«DRUG INTERACTIONS: Atazanavir/ritonavir ↓ lamotrigine Decreased lamotrigine AUC approximately 32%.»
FDA, section 7 · Open on DailyMed
Bupropion
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Bupropión»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«DRUG INTERACTIONS: Carbamazepine and carbamazepine epoxide ↓ lamotrigine Addition of carbamazepine decreases lamotrigine concentration approximately 40%.»
FDA, section 7 · Open on DailyMed
Clozapine
«Interacciones de lamotrigina con agentes psicoactivos: Los estudios in vitro indican que la formación del principal metabolito de lamotrigina, el 2-N-glucurónido, se vio mínimamente inhibida por la…»
AEMPS, section 4.5 · Open on CIMA
Estradiol
«En un estudio con 16 voluntarias, no se produjo ningún efecto en la farmacocinética del etinilestradiol de la píldora anticonceptiva oral en combinación con una dosis de 300 mg de lamotrigina en…»
AEMPS, section 4.5 · Open on CIMA
Ethinylestradiol
«DRUG INTERACTIONS: preparations containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel ↓ levonorgestrel Decrease in levonorgestrel component by 19%.»
FDA, section 7 · Open on DailyMed
Fluoxetine
«Interacciones de lamotrigina con agentes psicoactivos: Los estudios in vitro indican que la formación del principal metabolito de lamotrigina, el 2-N-glucurónido, se vio mínimamente inhibida por la…»
AEMPS, section 4.5 · Open on CIMA
Gabapentin
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Gabapentina»
AEMPS, section 4.5 · Open on CIMA
Haloperidol
«Interacciones de lamotrigina con agentes psicoactivos: Los estudios in vitro indican que la formación del principal metabolito de lamotrigina, el 2-N-glucurónido, se vio mínimamente inhibida por la…»
AEMPS, section 4.5 · Open on CIMA
hormonal contraceptivesclass named in the label
«DRUG INTERACTIONS: 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…»
FDA, section 7 · Open on DailyMed
Lacosamide
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Lacosamida»
AEMPS, section 4.5 · Open on CIMA
Levetiracetam
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Levetiracetam»
AEMPS, section 4.5 · Open on CIMA
Levonorgestrel
«DRUG INTERACTIONS: preparations containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel ↓ levonorgestrel Decrease in levonorgestrel component by 19%.»
FDA, section 7 · Open on DailyMed
Lithium
«Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Litio»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

ModerateEstradiol valerate + Dienogest
«Effects of Combined Oral Contraceptives on Other Drugs: COCs containing ethinyl estradiol may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma…»
FDA, section 7 · Open on DailyMed
ModerateLacosamide
«Lacosamida debe usarse con precaución en pacientes tratados con medicamentos conocidos por estar asociados con prolongación del PR (incluyendo los medicamentos antiepilépticos bloqueantes de canales…»
AEMPS, section 4.5 · Open on CIMA
ModerateOrlistat
«En pacientes tratados concomitantemente con orlistat y antiepilépticos, p. ej. valproato, lamotrigina, se han notificado convulsiones que no se puede descartar que sean debidas a una interacción. Por…»
AEMPS, section 4.5 · Open on CIMA
ModerateRitonavir
«Established and Other Potentially Significant Drug Interactions: Anticonvulsants: divalproex, lamotrigine, phenytoin ↓ anticonvulsants A dose increase may be needed for these drugs when…»
FDA, section 7 · Open on DailyMed
ModerateValproic acid
«Lamotrigina: Valproato sódico reduce el metabolismo de lamotrigina e incrementa la semivida media de lamotrigina casi dos veces. Esta interacción puede dar lugar a un incremento de la toxicidad de…»
AEMPS, section 4.5 · Open on CIMA
MinorZonisamide
«Posibles interacciones con otros medicamentos que afecten a Zonisamida: En estudios clínicos, la coadministración de lamotrigina no tuvo ningún efecto aparente en la farmacocinética de la zonisamida…»
AEMPS, section 4.5 · Open on CIMA
Aripiprazole
«Interacción de aripiprazol con otros medicamentos: Cuando se administra aripiprazol conjuntamente con valproato, litio o lamotrigina, no se han encontrado cambios clínicamente significativos en las…»
AEMPS, section 4.5 · Open on CIMA
Aripiprazole
«Drugs Having No Clinically Important Interactions with Aripiprazole: In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or…»
FDA, section 7 · Open on DailyMed
Atazanavir
«Established and Other Potentially Significant Drug Interactions: lamotrigine ↓ lamotrigine Coadministration of lamotrigine and atazanavir with ritonavir may require dosage adjustment of lamotrigine…»
FDA, section 7 · Open on DailyMed
Carbamazepine
«Fármacos que pueden disminuir los niveles plasmáticos de carbamazepina: Antiepilépticos: clobazam, lamotrigina, eslicarbazepina, tiagabina, topiramato, clonazepam, etosuximida, primidona, ácido…»
AEMPS, section 4.5 · Open on CIMA
Desogestrel
«Por consiguiente, las concentraciones plasmáticas y tisulares de otros principios activos pueden verse aumentadas (por ejemplo ciclosporina) o disminuidas (por ejemplo lamotrigina).»
AEMPS, section 4.5 · Open on CIMA
Eslicarbazepine acetate
«Lamotrigina: La glucuronidación es la principal vía metabólica tanto para la eslicarbazepina como la lamotrigina, y en consecuencia podría esperarse una interacción. Un estudio en sujetos sanos con…»
AEMPS, section 4.5 · Open on CIMA
Estradiol
«Se ha demostrado que los anticonceptivos hormonales que contienen estrógenos disminuyen significativamente las concentraciones plasmáticas de lamotrigina cuando se administran conjuntamente debido a…»
AEMPS, section 4.5 · Open on CIMA
Ethinylestradiol
«Los anticonceptivos orales (AOCs) pueden influir en el metabolismo de otros principios activos. En consecuencia, los niveles plasmáticos o tisulares pueden aumentar (p. ej. ciclosporina) o disminuir…»
AEMPS, section 4.5 · Open on CIMA
Levetiracetam
«Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Lamotrigine used for?

Lamotrigine is evaluated for the following indications with varying evidence strength: Focal epilepsy (evidence tier A), Bipolar disorder maintenance (evidence tier A), Mood stabilization (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Lamotrigine?

Common side effects of Lamotrigine (≥ 1 in 100): Rash (most often in the first 8 weeks), Headache, Dizziness, Drowsiness, Diplopia, Nausea. See the Safety section for uncommon and serious reactions.

Is Lamotrigine safe during pregnancy?

Is Lamotrigine compatible with breastfeeding?

Milk concentrations are high (about 30% of maternal plasma). Infant rash and sedation are possible – monitor activity, weight gain, and skin. If problems arise, switch to formula.

Who should not take Lamotrigine?

Lamotrigine is contraindicated in: Lamotrigine hypersensitivity; Age under 2 (most indications); Severe hepatic impairment. Full list in the Safety section.

Does Lamotrigine carry an FDA boxed warning?

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 09/23/2025
FDA / DailyMedLabel dated 08/13/2026

Other drugs in this group

Levetiracetam, Phenobarbital, Phenytoin, Pregabalin, Zonisamide, Eslicarbazepine acetate, Topiramate, Valproic acid