Lamotrigine Stats & Data
Nc1nnc(c(N)n1)c1cccc(Cl)c1ClPYZRQGJRPPTADH-UHFFFAOYSA-NPharmacology
DrugBankDescription
Lamotrigine is an antiepileptic drug belonging in the phenyltriazine class. It is used in the treatment of both epilepsy and as a mood stabilizer in bipolar disorder. Lamotrigine is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. It is approved for use in more than 30 countries. Lamotrigine has relatively few side-effects and does not require laboratory monitoring. While it is indicated for epilepsy and bipolar disorders, there is evidence that lamotrigine could have some clinical efficacy in certain neuropathic pain states.
Mechanism of Action
The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM. Weak inhibitory effects were observed at sigma opioid receptors.
Pharmacodynamics
Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity. A note on cardiovascular effects The metabolite of lamotrigine, 2-N-methyl metabolite (formed by glucuronidation), is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and at higher doses, complete AV block. Although this harmful metabolite is only found in trace amounts in humans, plasma concentrations may increase in conditions that cause decreased drug glucuronidation, such as liver disease.
Metabolism
Lamotrigine is mainly glucuronidated, forming 2-N-glucuronide conjugate, a pharmacologically inactive metabolite. The total radioactivity detected after a 240mg radiolabeled dose of lamotrigine during clinical trials were as follows: lamotrigine as unchanged drug(10%), a 2-N-glucuronide (76%), a 5-N-glucuronide (10%), a 2-N-methyl metabolite (0.14%), as well as various other minor metabolites (4%).
Absorption
Lamotrigine is rapidly and entirely absorbed with minimal first-pass metabolism effects, with a bioavailability estimated at 98%. Cmax is reached in the range of 1.4 to 4.8 hours post-dose, but this depends on the dose administered, concomitant medications, and epileptic status. The rate and extent of lamictal absorption is considered equivalent between the compressed tablet form taken with water to that of the chewable dispersible tablets, taken with or without water.
Toxicity
The oral LD50 in mouse and rat is 205 mg/kg and 245 mg/kg, respectively. Fatal cases of overdose of up to 15g of lamotrigine have been reported. Overdose with lamotrigine has been manifested by ataxia, nystagmus, increased seizures, decreased level of consciousness, coma, and intraventricular conduction delay. Though no known antidote exists for lamotrigine, hospitalization and general supportive measures should be employed in the case of a suspected lamotrigine overdose. Gastric lavage and emesis may be warranted with simultaneous protection of the airway. It is uncertain at this time whether hemodialysis is an effective means of removing lamotrigine from the sytemic circulation.
Indication
Lamotrigine is indicated as adjunctive therapy for the following seizure types in patients ≥2 years of age: partial seizures, primary generalized tonic-clonic seizures, and generalized seizures due to Lennox-Gastaut syndrome. It is also indicated for the process of conversion to drug monotherapy for those at least 16 years of age or older with partial seizures and currently are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). In addition to the above, lamotrigine is also indicated for the maintenance treatment of bipolar I disorder, delaying the time to mood episodes (which may include mania, hypomania, depression, mixed episodes) in adults at least 18 years or older, who have been treated for acute mood symptoms with standard therapy. Limitations of use It is important to note that lamotirigine should not be used in the treatment of acute mood episodes, as efficacy has not been established in this context.
Half-life
The average elimination half-life of lamotrigine ranges from approximately 14-59 hours. The value is dependent on the dose administered, concomitant drug therapy, as well as disease status. One pharmacokinetic study revealed a half-life of 22.8 to 37.4 hours in healthy volunteers. It also reported that enzyme-inducing antiepileptic drugs such as pheobarbital, phenytoin, or carbamazepine decrease the half-life of lamotrigine. On the other hand, valproic acid increases the half-life of lamotrigine (in the range of 48-59 hours).
Protein Binding
The plasma protein binding of lamotrigine is estimated at 55%. This drug is not expected to undergo clinically significant interactions with other drugs via competition for protein binding sites due its lower protein binding.
Elimination
Lamotrigine is excreted in both the urine and feces. Following oral administration of 240 mg radiolabelled lamotrigine, about 94% of total drug and its metabolites administered is recovered in the urine and 2% is recovered in the feces. One pharmacokinetic study recovered 43 to 87% of a lamotrigine dose in the urine mainly as glucuronidated metabolites. 2-N-glucuronide is mainly excreted in the urine.
Volume of Distribution
The mean apparent volume of distribution (Vd/F) of lamotrigine following oral administration ranges from 0.9 to 1.3 L/kg and is independent of dose administered. Lamotrigine accumulated in the kidney of the male rat, and likely behaves in a similar fashion in humans. Lamotrigine also binds to tissues containing melanin, such as the eyes and pigmented skin.
Clearance
The mean apparent plasma clearance (Cl/F) ranges from 0.18 to 1.21 mL/min/kg. The values vary depending on dosing regimen, concomitant antiepileptic medications, and disease state of the individual. In one study, healthy volunteers on lamictal monotherapy showed a clearance of about 0.44 mL/min/kg after a single dose.
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Lamotrigine is not typically associated with classical tolerance to its antiseizure or mood-stabilizing effects. Dose adjustments are based on clinical response and pharmacokinetic interactions rather than tolerance. Abrupt cessation can precipitate seizures; gradual taper is recommended.
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 31 experience reports (31 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 11
Adverse Effects 5
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Threshold (n=19) |
|---|---|
| Anxiety Suppression | 73.7% |
| Stimulation | 63.2% |
| Visual Distortions | 52.6% |
| Music Enhancement | 36.8% |
| Auditory Effects | 31.6% |
| Closed-Eye Visuals | 31.6% |
| Euphoria | 31.6% |
| Focus Enhancement | 31.6% |
| Color Enhancement | 31.6% |
| Hospital | 26.3% |
| Dissociation | 21.1% |
| Empathy | 21.1% |
| Memory Suppression | 21.1% |
| Introspection | 21.1% |
| Sedation | 15.8% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 31 experience reports.
Limited tier coverage — most reports fall within the Threshold range. Effects at other dose levels may not be represented.
| Effect | Threshold (n=19) | |
|---|---|---|
| anxiety suppression | ||
| stimulation | ||
| visual distortions | ||
| music enhancement | ||
| auditory effects | ||
| closed-eye visuals | ||
| euphoria | ||
| focus enhancement | ||
| color enhancement | ||
| hospital | ||
| dissociation | ||
| empathy | ||
| memory suppression | ||
| introspection | ||
| sedation | ||
| confusion | ||
| open-eye visuals | ||
| ego dissolution | ||
| seizure | ||
| body high |
Showing top 20 of 27 effects
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 59 individual dose entries
Oral (n=54)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 26 reports
Harm Reduction
drugs.wikiBoxed warning: Lamotrigine can cause serious skin reactions including Stevens–Johnson syndrome/toxic epidermal necrolysis; risk is highest 2–8 weeks after initiation and increases with high starting doses, rapid titration, and concurrent valproate. Discontinue at first sign of rash unless clearly non–drug-related; stopping may not prevent progression—seek urgent medical care. Serious systemic reactions (DRESS/anticonvulsant hypersensitivity) and hemophagocytic lymphohistiocytosis are rare but life-threatening; fever, lymphadenopathy, facial edema, hepatitis, or multi-organ signs require immediate evaluation. Lamotrigine half-life is prolonged to ~48–59 h with valproate and shortened to ~13.5–15 h with enzyme-inducing antiepileptics; removal or addition of inducers/inhibitors can markedly change levels, so doses often need adjustment. Estrogen-containing contraceptives can reduce lamotrigine exposure by about half during active-pill weeks with rebound increases during placebo weeks; some patients report intermenstrual bleeding and may require dose changes and/or level monitoring. During pregnancy, lamotrigine clearance increases (risk of breakthrough seizures/mood symptoms) and falls rapidly postpartum (toxicity risk if the pregnancy-up-titrated dose is not reduced); therapeutic drug monitoring or close clinical monitoring is recommended in these settings. If treatment is interrupted for several days, re-titration from a low dose is generally required to mitigate rash risk; do not resume the previous full dose without prescriber guidance. Overdose has caused ataxia, nystagmus, seizures, coma, and conduction abnormalities; there is no specific antidote—supportive care is indicated. Lamotrigine may cause false-positive phencyclidine (PCP) urine screens. Community reports suggest attenuated subjective effects of dissociatives (e.g., ketamine) and possibly classic psychedelics while on maintenance lamotrigine; this is anecdotal and should not prompt unsupervised dose omissions given the rash risk from improper re‑initiation.
References
Drugs.wiki References
- PubChem – Lamotrigine compound page
- StatPearls – Lamotrigine (boxed warning, titration, interactions)
- DrugBank – Lamotrigine drug card (PK ranges, overdose)
- DrugBank article – Lamotrigine clinical pharmacokinetics (half-life with inducers/inhibitor)
- DrugBank article – Combined oral contraceptive reduces lamotrigine exposure; breakthrough bleeding reported
- NCBI Bookshelf – The Epilepsies: Lamotrigine (rash risk, OC/pregnancy effects, TDM)
- LiverTox – Lamotrigine (DILI/DRESS, rapid escalation risk)
- LactMed – Lamotrigine during breastfeeding (infant exposure/monitoring)
- MotherToBaby – Lamotrigine pregnancy and breastfeeding factsheet
- DrugBank article – Lamotrigine-induced carbamazepine epoxide toxicity
- Reddit r/TherapeuticKetamine – clinician advice and user reports of ketamine blunting while on lamotrigine (anecdotal)
- Reddit r/KetamineTherapy – recent community discussion of skipping lamotrigine doses before ketamine (anecdotal)
- Bluelight – Lamotrigine general discussion thread (anecdotal experiences)