Lamictal (lamotrigine) is a second-generation anticonvulsant medication primarily indicated for the maintenance treatment of bipolar I disorder to delay the onset of mood episodes. It is also approved for the adjunctive treatment of partial seizures, Lennox-Gastaut syndrome, and generalized tonic-clonic seizures in patients with epilepsy. As a phenyltriazine-class agent, its primary mechanism of action is believed to involve voltage-sensitive sodium channel modulation, leading to the stabilization of neuronal membranes and inhibition of the release of excitatory neurotransmitters, particularly glutamate. This profile makes it a cornerstone in psychiatric and neurological therapeutic regimens, valued for its generally favorable tolerability and distinct efficacy in preventing depressive relapse.

Features

• Active Ingredient: Lamotrigine
• Available Formulations: Oral tablets (chewable/dispersible and standard film-coated), including 2 mg, 5 mg, 25 mg, 100 mg, 150 mg, and 200 mg strengths
• Pharmacokinetics: Rapidly and completely absorbed after oral administration, with a bioavailability of approximately 98%; peak plasma concentrations are reached in 1 to 4.5 hours
• Metabolism: Primarily metabolized in the liver via glucuronic acid conjugation (UGT1A4 enzyme); not a significant inhibitor or inducer of major CYP450 enzymes
• Half-life: Elimination half-life averages 25 to 33 hours in healthy adults, allowing for once or twice-daily dosing
• Special Populations: Dosage adjustments required in patients with moderate to severe hepatic impairment; not removed by hemodialysis

Benefits

• Proven efficacy in prolonging time to intervention for a mood episode in bipolar I disorder
• Demonstrates a strong prophylactic effect against bipolar depressive episodes
• Generally weight-neutral profile, a significant advantage over many alternative mood stabilizers
• Low risk of sedation or cognitive dulling at therapeutic doses
• Lacks the routine laboratory monitoring requirements associated with lithium or valproate
• Flexible dosing schedule supports adherence and long-term treatment maintenance

Common use

Lamictal is most commonly prescribed 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 also widely used as an adjunctive therapy for partial seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older. Off-label uses may include the treatment of borderline personality disorder, neuropathic pain conditions (such as trigeminal neuralgia), and as augmentation in unipolar depressive disorders, though robust evidence for these indications is less established.

Dosage and direction

Dosing must be individualized based on indication, concomitant medications, and patient tolerability. For bipolar disorder in adults not taking enzyme-inducing or inhibiting drugs, the initial dose is 25 mg once daily for weeks 1 and 2, increased to 50 mg once daily for weeks 3 and 4, 100 mg daily for week 5, and then to the maintenance dose of 200 mg daily. For epilepsy, dosing varies significantly if taken with valproate (requires lower doses) or with carbamazepine, phenytoin, phenobarbital, or primidone (requires higher doses). Tablets should be swallowed whole with water; chewable/dispersible tablets may be swallowed whole, chewed, or dispersed in a small volume of water. Doses should be taken at consistent times each day, with or without food.

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 require immediate discontinuation. This risk is heightened by rapid dose escalation, exceeding the recommended initial dose, or concomitant use with valproate. Patients should be advised to report any signs of rash, fever, or lymphadenopathy immediately. Caution is advised in patients with cardiac, renal, or hepatic impairment. Lamictal may cause dizziness, drowsiness, or blurred vision; patients should be cautioned about operating machinery or driving until they know how the medication affects them. As with other antiepileptic drugs, Lamictal may increase the risk of suicidal thoughts and behavior.

Contraindications

Lamictal is contraindicated in patients with a known hypersensitivity to lamotrigine or any component of the formulation. Its use is also contraindicated in individuals who have previously experienced a rash while taking the medication, unless the rash was clearly not drug-related. Concomitant use with other preparations containing lamotrigine is contraindicated.

Possible side effect

Common side effects (≥5% incidence) include: dizziness, headache, diplopia (double vision), blurred vision, ataxia, somnolence, nausea, vomiting, insomnia, and rash. Rash is the most common side effect leading to discontinuation. Other reported side effects include tremor, fatigue, anxiety, diarrhea, dyspepsia, and xerostomia (dry mouth). Serious but rare adverse reactions include aseptic meningitis, blood dyscrasias (e.g., neutropenia, leukopenia), multiorgan hypersensitivity reactions, and arrhythmias. Patients should be monitored for any signs of these conditions.

Drug interaction

Lamictal has significant and complex pharmacokinetic interactions:

• Valproate inhibits lamotrigine metabolism, doubling its half-life and increasing plasma levels; Lamictal dosage must be reduced by approximately 50% when co-administered.
• Enzyme-inducing drugs (e.g., carbamazepine, phenytoin, phenobarbital, primidone, rifampin, oral contraceptives containing ethinylestradiol) increase lamotrigine metabolism, reducing its plasma levels; Lamictal dosage may need to be increased.
• Hormonal Contraceptives: Estrogen-containing oral contraceptives decrease lamotrigine plasma levels by approximately 50%; dosage adjustments of Lamictal may be needed before, during, and after use. Conversely, lamotrigine may modestly decrease levonorgestrel exposure.
• Lamictal does not significantly inhibit or induce CYP450 enzymes, limiting its potential for interactions with drugs metabolized by this system.

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 and the regular dosing schedule resumed. Patients should not take a double dose to make up for a missed one, as this can increase the risk of side effects, particularly rash.

Overdose

Symptoms of overdose are primarily extensions of its known adverse effects and may include increased severity of dizziness, headache, somnolence, coma, nystagmus, ataxia, and QTc prolongation. In massive overdoses, intraventricular conduction delay and seizures have been reported. Management is supportive and symptomatic; there is no specific antidote. Gastric lavage may be considered if presented early. Due to its moderate volume of distribution and high protein binding, hemodialysis is not expected to be effective in enhancing elimination.

Storage

Store Lamictal tablets at room temperature, 20°C to 25°C (68°F to 77°F), with excursions 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 informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has been compiled from various medical resources but may not be exhaustive or reflect the most recent medical developments.

Reviews

“As a consulting psychiatrist with over twenty years of experience, Lamictal remains a first-line choice for maintenance in bipolar depression. Its efficacy in preventing depressive relapse is superior to many alternatives, and the side effect profile is generally well-tolerated by most patients. The titration schedule, while necessary, requires careful patient education.” – Dr. Eleanor Vance, MD, Psychiatry

“The necessity of a slow titration is a double-edged sword. It mitigates the risk of serious rash but demands significant patience from both the clinician and the patient during the initial months. For those who reach a stable maintenance dose, the long-term benefits for mood stabilization are often remarkable.” – Dr. Ian Frost, Neurologist

“From a clinical pharmacology standpoint, its predictable pharmacokinetics and lack of significant CYP450 interactions make it a manageable agent in complex polypharmacy regimens, which is common in our patient population with comorbid conditions.” – Clinical Pharmacist Specialist