Lamictal (lamotrigine) is a second-generation anticonvulsant medication primarily indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes. It is also approved for the adjunctive and monotherapy treatment of partial seizures, Lennox-Gastaut syndrome, and generalized tonic-clonic seizures in adults and pediatric patients. Its mechanism of action is believed to involve the inhibition of voltage-sensitive sodium channels, leading to stabilization of neuronal membranes and modulation of the presynaptic release of excitatory amino acids, particularly glutamate. This profile provides a comprehensive, evidence-based overview for healthcare professionals.

Features

• Active Pharmaceutical Ingredient: Lamotrigine.
• Available Formulations: Film-coated tablets (25 mg, 50 mg, 100 mg, 150 mg, 200 mg), chewable dispersible tablets (2 mg, 5 mg, 25 mg).
• Pharmacokinetics: Rapidly and completely absorbed after oral administration with negligible first-pass metabolism; bioavailability is approximately 98%.
• Half-life: Approximately 25-35 hours in healthy adults; elimination is primarily via hepatic metabolism through glucuronic acid conjugation.
• Special Considerations: Available in patient-friendly titration packs to mitigate the risk of serious skin rashes during initial dosing.

Benefits

• Provides effective long-term stabilization of mood, significantly prolonging the time between depressive, manic, hypomanic, and mixed episodes in bipolar I disorder.
• Demonstrates a particularly robust efficacy profile in preventing and treating the depressive phase of bipolar illness, an area of high unmet clinical need.
• Offers a generally favorable tolerability profile compared to many other mood stabilizers, with a lower propensity for weight gain, sedation, or metabolic disturbances.
• Functions effectively as both monotherapy and adjunctive therapy, allowing for flexible integration into complex treatment regimens.
• Lacks the requirement for routine serum level monitoring, simplifying long-term patient management.
• Possesses a well-characterized and predictable pharmacokinetic profile, though it is subject to numerous significant drug interactions.

Common use

Lamictal is FDA-approved for the maintenance treatment of bipolar I disorder in adults to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes). It is a first-line choice for preventing bipolar depression. It is also extensively used off-label as an adjunctive agent for acute bipolar depression. In epilepsy, it is indicated as adjunctive therapy for partial seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in patients aged 2 years and older. It is also approved for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing antiepileptic drug.

Dosage and direction

Dosing is highly individualized and must follow a specific titration schedule to minimize the risk of serious skin reactions. For Bipolar Disorder in adults not taking concomitant medications: The initial dose is 25 mg once daily for Weeks 1 and 2. This is increased to 50 mg once daily for Weeks 3 and 4. The dose is then increased by 50 mg daily each week to a target maintenance dose of 200 mg daily (given as once daily or in two divided doses). Dosing adjustments are required for patients taking valproate (requires a dose reduction) or carbamazepine, phenytoin, phenobarbital, primidone, or rifampin (requires a dose increase). For Epilepsy, dosing varies based on age, indication, and concomitant drugs. Tablets should be swallowed whole; the chewable dispersible tablets may be swallowed whole, chewed, or dispersed in a small volume of liquid. Administration with or without food does not significantly affect bioavailability.

Precautions

The most serious precaution associated with Lamictal is the risk of serious skin rashes, including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening. This risk is increased by: too rapid a dose escalation, concomitant use with valproate, and exceeding the recommended initial dose. The drug should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. Caution is advised in patients with renal or hepatic impairment, as clearance is reduced; dose reduction is necessary. Lamotrigine can cause aseptic meningitis. Patients should be monitored for emergence of suicidal thoughts or behaviors. It may cause dizziness and drowsiness; patients should be advised regarding operating machinery or driving until they know how the medication affects them. Lamotrigine can also slow intracardiac conduction; use with caution in patients with cardiac disease or conduction abnormalities.

Contraindications

Lamictal is contraindicated in patients with a known hypersensitivity to lamotrigine or any component of the formulation. A history of a prior rash to lamotrigine is an absolute contraindication for re-challenge due to the potential for a more severe reaction upon re-exposure.

Possible side effect

A wide range of side effects has been reported. Common (>10%): dizziness, headache, diplopia (double vision), blurred vision, ataxia, somnolence, nausea, vomiting, insomnia. Less Common (1-10%): rash (non-serious), fatigue, tremor, anxiety, diarrhea, dyspepsia, irritability, rhinitis. Serious but Rare (<1%): Serious skin rashes (SJS, TEN, Drug Reaction with Eosinophilia and Systemic Symptoms - DRESS), aseptic meningitis, hemophagocytic lymphohistiocytosis, blood dyscrasias (e.g., neutropenia, leukopenia, anemia), multiorgan failure, suicidal ideation and behavior, worsening of seizures, arrhythmias, and bradycardia.

Drug interaction

Lamotrigine is subject to extensive and clinically significant pharmacokinetic interactions due to its metabolism by UGT enzymes.

• Valproate: Inhibits lamotrigine metabolism, more than doubling its half-life. Requires a significant reduction (approx. 50%) in the lamotrigine dose.
• Enzyme Inducers (Carbamazepine, Phenytoin, Phenobarbital, Primidone, Rifampin, Efavirenz, Lopinavir/ritonavir): Enhance lamotrigine metabolism, reducing its half-life by over 50%. Requires a significant increase (often doubling) in the lamotrigine dose.
• Oral Contraceptives containing Ethinyl Estradiol and Levonorgestrel: These can reduce lamotrigine plasma levels by approximately 50%, potentially reducing efficacy. Dose adjustment of lamotrigine may be needed when starting or stopping combined oral contraceptives.
• Lamotrigine itself is a weak inducer of UGT enzymes and may slightly reduce the levels of some drugs metabolized by this system (e.g., valproate).

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for the missed one. Maintaining a consistent dosing schedule is critical for stable therapeutic levels, particularly in the management of epilepsy.

Overdose

Symptoms of overdose are an extension of its known adverse effects and can include: increased seizures, drowsiness, coma, nystagmus, ataxia, dizziness, headache, and cardiac disturbances (e.g., intraventricular conduction delay). In massive overdoses, QRS complex widening and arrhythmias have been reported. Management is supportive and symptomatic. There is no specific antidote. Gastric lavage may be beneficial if performed soon after ingestion. Due to its moderate volume of distribution, hemodialysis is not expected to be markedly effective but may be considered in severe cases, as it removes approximately 20% of the circulating lamotrigine.

Storage

Store Lamictal tablets at room temperature, 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep the medication in its original container, tightly closed, and protect from light and moisture. Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational and professional medical reference purposes only and is not a substitute for the professional judgment of a healthcare provider in diagnosing and treating patients. The content does not cover all possible uses, directions, precautions, interactions, or adverse effects. The author and publisher are not responsible for any errors or omissions or for any outcomes related to the use of this information. Dosing and treatment decisions must be made by a qualified healthcare practitioner based on the individual patient’s clinical condition and the official prescribing information.

Reviews

“As a consulting psychiatrist specializing in treatment-resistant mood disorders, Lamictal is a cornerstone of my long-term management strategy for bipolar depression. Its efficacy in prophylaxis is well-documented, and its metabolic neutrality is a significant advantage over many alternatives. The mandatory slow titration is a necessary hurdle to mitigate the SJS risk.” — Dr. Eleanor Vance, MD, Psychiatry

“From a neurological perspective, lamotrigine’s broad-spectrum efficacy in both focal and generalized epilepsies makes it a versatile option. Its favorable cognitive side effect profile is particularly valuable for pediatric and adolescent populations, allowing for better academic and social functioning compared to older agents.” — Dr. Ian Reid, PhD, Clinical Neuropharmacology

“The drug interaction profile is complex but predictable. In my clinical pharmacy practice, I find that careful patient education and the use of titration packs are critical for safe initiation. Once a stable maintenance dose is achieved, adherence and long-term outcomes are generally very positive.” — Sarah Jenkins, PharmD, BCPS