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Lamotrigine - Uses, Mechanism of Action, Precautions, and Side Effects

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12 min read


Lamotrigine is a drug that treats seizures in individuals with epilepsy and controls certain mood disorders, such as bipolar disorder.

Medically reviewed by

Dr. Basuki Nath Bhagat

Published At March 9, 2023
Reviewed AtMarch 9, 2023


Lamotrigine is an antiepileptic drug, also known as an anticonvulsant. It belongs to the phenyltriazine class. It is used in the treatment of seizures as well as acts as a mood pacifier in people with bipolar disorder. It is the first medication since Lithium that has been granted Food and Drug Administration (FDA) approval for managing bipolar disorder type I.

Important Warning: Lamotrigine might cause a life-threatening skin rash in individuals starting with a very high dose. Immediate emergency attention is required in case one develops a skin rash, hives, blisters, peeling, mouth sores, or sores around the mouth.

How Does Lamotrigine Work?

Lamotrigine belongs to a class of anticonvulsants or antiepileptic drugs (AEDs). These drugs are used to treat the same kind of conditions. For example, in epileptic patients, Lamotrigine reduces the release of a substance known as glutamate in the brain, thus preventing the brain neurons from becoming very active. This results in lesser seizures. In people with bipolar disorder, Lamotrigine might affect some receptors in the brain that control one's mood, decreasing the number of mood swings.

Uses of Lamotrigine:

Lamotrigine is indicated in the following -

  • Epilepsy - Lamotrigine is used as adjunctive therapy for specific seizure types in patients two years and above. Seizures such as partial-onset seizures, primary generalized tonic-clonic (PGTC) seizures, and generalized seizures of Lennox-Gastaut syndrome. Lamotrigine is used for the conversion to monotherapy in adults with partial-onset seizures who are undergoing treatment with Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate.

  • Bipolar Disorder - Lamotrigine is used for the maintenance treatment of bipolar disorder type I to delay the frequency of mood changes such as depression, mania, hypomania, etc. However, the efficacy of Lamotrigine in the treatment of acute mood disorders has not been found.


Lamotrigine should not be used in treating acute mood disorders, as its efficiency has not been confirmed.

Dosage Restrictions:

1. Route of Administration - Oral.

2. Dosage Strengths -

  • Tablet - 25 mg, 100 mg, 150 mg, 200 mg.

  • Chewable Tablet - 2 mg, 5 mg, 200 mg.

  • Oral-Disintegrating Tablet - 25 mg, 50 mg, 100 mg, 200 mg.

  • Extended-Release Tablet - 25 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg.

3. Dosage Forms -

  • Tablet - White/peach/cream/blue, scored shield-shaped tablets debossed with a logo and tablet strength.

  • Chewable Dispersible Tablets - White to off-white round/caplet-shaped/super-elliptical shaped debossed with the logo and strength.

  • Orally Disintegrating Tablets - White to off-white, round, flare-faced, radius-edged tablets debossed with the logo on one side and strength on the other.

Special Considerations:

  • Pregnancy - Lamotrigine can be taken during pregnancy if needed. Lamotrigine should not be stopped in case one becomes pregnant. The doctor should be informed in such instances. The baby might need careful monitoring for a few days after birth.

  • Breastfeeding - One can take Lamotrigine while breastfeeding if the baby is healthy. The dose of the drug can be reduced after delivery. Do not stop Lamotrigine without the doctor's consent. Lamotrigine can pass in breast milk in different amounts. If the baby shows signs of drowsiness, skin rash, poor feeding, and flabby muscles, they should be taken to the hospital as soon as possible.

  • Children - Lamotrigine is indicated in kids above two years of age for partial onset seizures, generalized seizures of Lennox-gastaut syndrome, and primary generalized tonic-clonic (PGTC) seizures.

  • Elderly - The dose selection of an elderly patient should be careful, starting with the lower dosage.

Warnings and Contraindications:

Lamotrigine is contraindicated in patients with hypersensitivity such as rash, angioedema (sudden swelling of a body part), acute urticaria (itchy rash on the skin), extensive pruritus (itching), mucosal ulceration to the drug or any of its constituents.

Warnings and Precautions:

  • Severe Skin Rashes - In kids aged two to 16 and adults, painful, life-threatening rashes have been reported. Furthermore, including Valproate in a multidrug regimen has increased the risk of severe, life-threatening inflammation in children and adults. The risk of developing skin rashes increases by increasing the recommended dosage for individuals allergic to other antiepileptic drugs.

  • Multiorgan Hypersensitivity Reactions and Organ Failure - Multiorgan hypersensitivity reactions, also known as drug reactions with eosinophilia and systemic symptoms (DRESS), have been found to occur with Lamotrigine. It usually presents with fever, rash, and lymphadenopathy in patients with hepatitis, nephritis, hematologic abnormalities, myocarditis (inflammation of the heart), or myositis, resembling acute viral infection. Eosinophilia is also present.

  • Blood Dyscrasias - Blood dyscrasias such as neutropenia, leukopenia, anemia, thrombocytopenia (less platelets), pancytopenia (less red blood cells), aplastic anemia, and red cell aplasia have seldom been found associated with DRESS (drug reaction with eosinophilia and systemic symptoms).

  • Suicidal Behavior - Lamotrigine has been found to increase the risk of suicidal thoughts or behavior.

  • Bipolar Disorder - The effectiveness of Lamotrigine in treating acute bipolar disorder has not been established. In addition, the safety and efficacy of Lamotrigine in children less than 18 years of age with bipolar disorder have not been found. Patients with a history of suicidal behavior and young adults are at an increased risk and require extensive monitoring during treatment.

  • Aseptic Meningitis - Lamotrigine increases the risk of developing aseptic meningitis.

  • Use With Oral Contraceptives - Estrogen-containing oral contraceptives have been found to reduce the serum concentration of Lamotrigine. Therefore, dosage adjustment is needed in such cases.

  • Withdrawal Seizures - In patients with epilepsy, there is an increased possibility of withdrawal seizures in case of abrupt discontinuation. Sudden unexplained death in epilepsy (SUDEP) has been reported in certain patients. Lamotrigine tends to bind to the eye and other melanin-containing tissues.

For Patients:

What Is a Seizure?

A seizure is a sudden, uncontrolled disturbance in the brain. It can cause changed behavior, movements, and levels of consciousness. Two or more seizures around twenty-four hours apart that are not due to an identifiable cause are known as epilepsy.

Why Is Lamotrigine Prescribed for Seizure?

Lamotrigine is used with other medications to treat certain kinds of seizures in patients with epilepsy. All Lamotrigine tablets, apart from the extended-release tablets, are used alone or with other medicines to treat seizures in people with epilepsy. The various Lamotrigine tablets, except for the extended-release tablets, also increase the duration between the multiple episodes of mood disorders in people with bipolar disorder. Lamotrigine falls under a class of medications known as anticonvulsants. It reduces unusual, abnormal electrical activity in the brain.

How to Take Lamotrigine?

  • Lamotrigine is available as a tablet, an extended-release tablet, an orally disintegrating tablet, and a chewable dispersible tablet that is taken orally with or without food.

  • The extended-release tablets can be taken once a day. The orally disintegrating tablets and chewable dispersible tablets are taken once or twice a day. The prescription should be followed for proper direction.

  • Other medications with similar names should be avoided by careful monitoring.

  • Swallow the tablets and extended-release tablets whole. Do not split, chew, or crush them.

  • The chewable tablets can be chewed, dissolved, or swallowed whole. Therefore, keep a single pill and use it.

  • While taking, an orally disintegrating tablet should be kept on the tongue and turned around the mouth. After a few seconds, swallow it with or without water.

  • Do not use broken tablets.

  • In case one is switching from previous seizure medication to Lamotrigine, follow the directions given by the doctor.

  • The medicine should be taken daily without fail.

What to Discuss With the Doctor Before Beginning Lamotrigine?

Before beginning the medication, inform the doctor:

  • About any allergy to Lamotrigine or its constituents.

  • Allergy to any other medication.

  • The medications one takes include prescription drugs, vitamins, nutritional supplements, and herbal products.

  • About the use of hormonal contraceptives or hormone replacement therapy.

  • In case one had an autoimmune disease (a condition in which the body attacks its organs, causing loss of function) such as lupus, a blood disorder, depression, mood swings, suicidal thoughts, heart failure, irregular heartbeats, kidney or liver diseases, or ascites (abdominal swelling caused by liver disease).

  • If one is pregnant, plans to become pregnant, or becomes pregnant while taking Lamotrigine, the doctor should be informed.

  • If one is breastfeeding, the doctor should be informed.

  • In case Lamotrigine is making one sleepy or drowsy, refrain from driving a car or using machines.

  • One should also know that Lamotrigine taken for treating epilepsy, or mental illness, might make one suicidal. There is a risk involved with Lamotrigine, but if the condition remains untreated, it might worsen the present mental health condition.

Is Lamotrigine Safe?

Lamotrigine might cause severe adverse reactions like skin rashes, multiorgan hypersensitivity, and organ damage. In the long run, it can cause osteoporosis, or osteopenia, increasing one's chances of breaking a bone.

Is Lamotrigine Effective?

Lamotrigine controls the seizure attacks but does not cure them. It takes many weeks to feel better. The medication should be continued even if one feels better.

What Side Effects Can be Expected With Lamotrigine?

  • Blurry vision or vision changes.

  • Pain or discomfort in the chest.

  • Clumsiness.

  • Reduced urine output.

  • Dilated neck blood vessels.

  • Double vision.

  • Irregular breathing.

  • Nausea.

  • Pain in the arms, jaw, back, or neck.

  • Difficulty in coordination.

  • Continuous seizures.

  • Skin rashes.

  • Sweating, swelling of the face, fingers, feet, or lower legs.

  • Difficulty in breathing.

  • Tiredness.

  • Vomiting.

  • Weight gain.

  • Difficulty in swallowing.

  • Frequent seizures.

  • Swollen lymph nodes.

  • Sore throat, fever, chills, ear pain, pink eye, or fainting.

  • Unusual bleeding.

  • Missed periods.

  • Uncontrollable shaking on a body part.

Can One Stop Taking Lamotrigine Without the Doctor's Approval?

Lamotrigine should not be stopped without the doctor's permission, even after experiencing side effects. Instead, the doctor might decrease the dose gradually.

Are There Any Dietary Restrictions to Consider When Taking Lamotrigine?

No dietary precautions should be taken unless advised by the doctor.

How Should One Store Lamotrigine?

Lamotrigine should be stored at room temperature, in a dry place, and away from light.

It should be kept away from the reach of children.

How Should One Dispose of Lamotrigine?

  • Lamotrigine should be disposed of so that pets, kids, and any other person cannot consume it.

  • It should not be thrown in the toilet.

  • The best way to dispose of Lamotrigine is by a medicine take-back program by seeking information from a pharmacist.

What To Do in Case of Overdose?

In case of an overdose, hospitalization of the individual is advised. The vital signs are closely monitored. Vomiting might be induced. Hemodialysis could effectively remove Lamotrigine from the blood, although the effectiveness remains doubtful. A poison control center should be contacted in case of an overdose of Lamotrigine.

For Doctors


  • Anti-Seizure Drug - Lamotrigine is an anti-seizure or antiepileptic drug that was first approved in the USA in 1994. It is considered the first line of treatment for generalized tonic-clonic seizures, including simple and complex partial seizures,focal-onset tonic-clonic seizures, and Lennox-Gastaut syndrome.

  • Bipolar Depression - It is also used to treat rapid-cycling bipolar depression and maintain bipolar disorder type I.

  • As a preventive treatment for basilar migraine with aura, panic disorder, and binge eating disorder.

  • Managing trigeminal neuralgia.

What Is the Pharmacology of Lamotrigine?

Description - Lamotrigine is a member of the phenyltriazine class of drugs. The chemical name is 3,5- diamino-6-(2,3-chlorophenyl)-as-triazine. The molecular formula is C9H7N5Cl2, and the molecular weight is 256.09. It is a pale white to cream-colored powder and is slightly soluble in water and 0.1 M of HCL.


1. Active Ingredients - Lamotrigine.

2. Inactive Ingredients -

  • Lactose.

  • Magnesium stearate.

  • Microcrystalline cellulose.

  • Povidone.

  • Sodium starch glycolate.

  • FD&C yellow no. 6 lake (100 mg tablet only).

  • Ferric oxide yellow (150 mg tablet only).

  • FD&C blue no. 2 lake (200 mg tablet only).

Clinical Pharmacology:

Mechanism of Action - The exact mechanism by which Lamotrigine deploys its anticonvulsant action is not known. Lamotrigine is effective in preventing the spread of seizures in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests and also stopped seizures in the visually and electrically evoked after-discharge (EEAD) tests for the antiepileptic activity. An effect on sodium channels is also one of the mechanisms of action of Lamotrigine. Some studies also suggest that Lamotrigine inhibits the voltage-sensitive sodium channels, thus stabilizing neuronal membranes, and modulates presynaptic transmitter release of excitatory amino acids.


  • Folate Metabolism - Lamotrigine inhibits dihydrofolate reductase, which might interfere with the biosynthesis of nucleic acids and proteins.

  • Accumulation in the kidneys - Lamotrigine accumulates in the kidneys causing chronic progressive nephrosis, necrosis, and mineralization.

  • Melanin Binding - Lamotrigine binds to melanin-containing tissues, such as the eyes and pigmented skin.

  • Cardiovascular - Lamotrigine is assimilated to a 2-N-methyl metabolite. This metabolite causes an increase in the dose-dependent PR interval, widening the QRS complex and complete AV conduction block in higher doses.


  • Mean Cmax - Cmax is In the range of 1.4 to 4.8 hours post-dose.

  • Median Tmax- 1.3 hours post-dose.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose]

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose]

Pharmacokinetic Changes - Lamotrigine is well absorbed, with bioavailability reaching around 100 %. The absorption remains unaffected by food, and there is no first-pass metabolism.

A. Distribution-

  • Protein Bound - 55 %.

  • Volume of Distribution - 0.9 - 1.3 L/kg.

  • Steady-state Plasma Levels - The value of serum Lamotrigine, on average, is 12.7 % lower.

  • Time to Approach Steady-state Levels - Three to seven days.

  • Binding to Plasma Proteins - 56 %.

B. Metabolism - Lamotrigine is metabolized by glucuronic acid conjugation. The most crucial metabolite is an inactive 2-N glucuronide conjugate.

C. Excretion -

  • Recovery - 94 % of the medication was recovered in the urine and two percent in the feces.

D. Elimination - Total body clearance is 0.4 to 1.1 mL/min/kg.

Special Considerations:

  • Pregnancy - The physiological changes during pregnancy might affect Lamotrigine concentrations or therapeutic effects. There have been reduced Lamotrigine concentrations during pregnancy and restoration of the pre-partum concentration after the delivery. Dose adjustment is recommended to maintain the clinical response.

  • Labor and Delivery - Lamotrigine's effect on labor and delivery remains unknown.

  • Nursing Mothers - Lamotrigine is present in the milk. The Lamotrigine plasma levels in breastfed infants are as high as 50 % of the mother's serum levels. Therefore, breastfeeding should be discontinued in infants with Lamotrigine toxicity.

  • Pediatric Use - Lamotrigine is indicated in kids above two years of age for partial onset seizures, generalized seizures of Lennox-gastaut syndrome, and PGTC seizures.

  • Geriatric Use - The dose selection of an elderly patient should be made carefully, starting at the lower end of the dosing.

  • Hepatic Impairment - No dose alteration is required in patients with mild cases of liver impairment. In moderate liver impairment, the dose should be reduced by 25 %, and in people with severe hepatic impairment, the amount should be reduced by 50 %.

  • Renal Impairment - Initial doses of Lamotrigine are based on the patient's AED regimens, and reduced maintenance doses might be effective in patients with significant renal impairment.

Drug Interactions:

  • 1, 2-Benzodiazepine - 1, 2-Benzodiazepine might increase the central nervous system depressant effect of Lamotrigine.

  • Abacavir - The metabolism of Abacavir is increased when combined with Lamotrigine.

  • Acebutolol - Lamotrigine might increase the arrhythmogenic activities of Acebutolol.

What Have Clinical Trials Shown Concerning Anastrozole?

Monotherapy With Lamictal in Adults With Partial-onset Seizures Receiving Treatment With Carbamazepine, Phenytoin, Phenobarbital, or Primidone as the Single Antiepileptic Drug (AED) -

A multicenter, double-blind clinical trial with 156 patients having partial seizures has been performed. The patients experienced around four simple partial-onset, complex partial-onset, and secondarily generalized seizures in four weeks of receiving Carbamazepine or Phenytoin monotherapy.

Trial Endpoints - The trial endpoints were the completion of trial treatment or meeting escape criteria:

  • Doubling the monthly count of seizures.

  • Doubling of the highest 2-day frequency of seizure.

  • A new type of seizure.

  • Prolongation of generalized tonic-clonic seizures.

The primary efficiency was the percentage of patients who met the escape criteria.

Results - Around 42 % of the patients receiving Lamotrigine met the escape criteria, and 69 % were in the valproate group. The difference in the patients meeting escape criteria was in favor of Lamotrigine. No differences in efficiency based on age, sex, or race were found.

Patient Counseling Information:

The patient should be advised to read the FDA-approved patient labeling.

  • Rash - Before starting with Lamotrigine, the patient should be informed about the inflammation and other signs and symptoms of hypersensitivity.

  • Multiorgan Hypersensitivity Reactions - The patients should be informed about multiorgan hypersensitivity reactions and acute multiorgan failure that might occur with Lamotrigine.

  • Suicidal Thinking and Behaviour - The patients and their caretakers should be informed that Lamotrigine might increase suicidal thoughts. They should be instructed to be vigilant of any unusual changes in behavior.

  • Worsening of the Seizures - The patients should be asked to report to a doctor in case their seizures worsen.

  • Central Nervous System - The patient should be informed that Lamotrigine might cause dizziness, drowsiness, and other central nervous system depression symptoms.

  • Pregnancy and Breastfeeding - The patient should be instructed to tell their doctor if they become pregnant, or planning to get pregnant, or if they intend to breastfeed. The patient should be asked to enroll in the NAAED pregnancy registry in case of pregnancy. Patients who tend to breastfeed should be informed about the presence of Lamotrigine in breast milk.

  • Oral Contraceptives - The patient should inform the doctor if they plan to begin or stop oral contraceptive use.

  • Discontinuation of Lamotrigine - The patient should be advised not to stop the medication without the doctor's consent.

  • Aseptic Meningitis - The patient should be informed that Lamotrigine may cause aseptic meningitis. Instruct them to notify their doctor if they develop headaches, fever, nausea, vomiting, neck stiffness, myalgia, chills, confusion, etc.

  • Medicine Error - In order to avoid a medicine error, advise the patients to inspect their tablets every time they refill their prescriptions.

Administration Instructions:

Lamotrigine orally disintegrating tablets should be kept on the tongue. Then, it can be swallowed with or without water. The tablet can be consumed with or without food.

Lamotrigine chewable dispersible tablets can be swallowed as it is, chewed, or dissolved in water or fruit juice.

Complications or Side Effects:

  • Serious skin rashes.

  • Multiorgan hypersensitivity reaction and organ failure.

  • Blood dyscrasias.

  • Increased suicidal tendency.

  • Aseptic meningitis.

  • Blurry vision or vision changes.

  • Pain or discomfort in the chest.

  • Clumsiness.

  • Reduced urine output.

  • Dilated neck blood vessels.

  • Double vision.

  • Irregular breathing.

  • Nausea.

  • Pain in the arms, jaw, back, or neck.

  • Difficulty in coordination.

  • Continuous seizures.

  • Sweating, swelling of the face, fingers, feet, or lower legs.

  • Difficulty in breathing.

  • Tiredness.

  • Vomiting.

  • Weight gain.

  • Difficulty in swallowing.

  • Frequent seizures.

  • Swollen lymph nodes.

  • Sore throat, fever, chills, ear pain, pink eye, or fainting.

  • Unusual bleeding.

  • Missed periods.

Source Article IclonSourcesSource Article Arrow
Dr. Basuki Nath Bhagat
Dr. Basuki Nath Bhagat

Family Physician


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