Lamictal: Stabilizing Mood with Precision-Targeted Therapy
Lamictal
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Lamictal (lamotrigine) is an anticonvulsant and mood-stabilizing medication primarily indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adults. It is also approved for the adjunctive therapy of partial seizures, primary generalized tonic-clonic seizures, and generalized seizures of Lennox-Gastaut syndrome in patients aged 2 years and older. As a phenyltriazine-class antiepileptic drug (AED), its mechanism of action is believed to involve the inhibition of voltage-sensitive sodium channels, leading to stabilization of neuronal membranes and modulation of presynaptic transmitter release of excitatory amino acids, such as glutamate and aspartate. Its distinct neurochemical profile offers a favorable side effect spectrum for long-term management, particularly noted for its efficacy in treating the depressive phase of bipolar disorder without the common metabolic side effects associated with many atypical antipsychotics.
Features
- Active Ingredient: Lamotrigine
- Available Formulations: Tablets (chewable/dispersible and standard film-coated), orally disintegrating tablets
- Standard Strengths: 2 mg, 5 mg, 25 mg, 100 mg, 150 mg, 200 mg
- Therapeutic Class: Anticonvulsant, Mood Stabilizer
- Mechanism of Action: Voltage-gated sodium channel blockade; putative glutamate release inhibition
- Half-Life: Approximately 24–35 hours in healthy adults; may be altered by concomitant medications
- Bioavailability: ~98% following oral administration
- Metabolism: Primarily hepatic via glucuronic acid conjugation (UGT1A4)
Benefits
- Provides effective long-term stabilization of mood, significantly reducing the frequency and severity of depressive and manic episodes in bipolar I disorder.
- Offers a favorable weight-neutral profile, unlike many other mood stabilizers and atypical antipsychotics, supporting long-term metabolic health.
- Demonstrates efficacy as adjunctive therapy for various seizure types, improving overall seizure control in treatment-resistant epilepsy.
- Features a generally well-tolerated side effect profile in maintenance phases, with a lower incidence of sedation or cognitive dulling compared to some alternatives.
- Allows for flexible dosing regimens that can be tailored to individual patient response and concomitant therapies.
- Serves as a foundational monotherapy option for bipolar depression, addressing a critical unmet need in mood disorder pharmacotherapy.
Common use
Lamictal is most commonly prescribed for the maintenance treatment of bipolar I disorder in adults to prolong the time between episodes of depression, mania, or hypomania. It is recognized for its particular strength in preventing depressive relapse, a challenging aspect of bipolar management. In neurology, it is widely used as an adjunctive therapy for partial seizures, generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older. Off-label, it is sometimes utilized in the treatment of borderline personality disorder, neuropathic pain conditions (such as trigeminal neuralgia), and as augmentation in unipolar depression, though robust evidence for these uses is more limited. Its use is always initiated under careful medical supervision due to the risk of serious cutaneous reactions.
Dosage and direction
Dosing of Lamictal is highly individualized and must be titrated slowly to mitigate the risk of serious skin rashes, including Stevens-Johnson Syndrome (SJS). For bipolar disorder maintenance in adults not taking enzyme-inducing or inhibiting drugs, the initial dose is 25 mg once daily for weeks 1–2, increased to 50 mg daily for weeks 3–4, then to 100 mg daily in week 5, with a target maintenance dose of 200 mg daily reached by week 6. Doses may be adjusted based on clinical response and tolerability.
For adjunctive epilepsy therapy, dosing varies based on the patient’s age and concomitant AEDs. In adults and adolescents over 12 years taking valproate, the initial dose is lower (25 mg every other day for weeks 1–2), with a slower titration schedule. Those taking enzyme-inducing AEDs (like carbamazepine) without valproate require higher initial doses (50 mg daily). Dosing in pediatric patients (2–12 years) is weight-based and follows specific titration tables provided in prescribing information. Tablets should be swallowed whole with water; chewable/dispersible tablets may be chewed, dispersed in water, or swallowed whole. Doses are typically administered once or twice daily.
Precautions
The most serious precaution associated with Lamictal is the risk of life-threatening skin rashes, including SJS and toxic epidermal necrolysis (TEN). The risk is highest in the first 2–8 weeks of therapy, in pediatric patients, and with rapid dose escalation. Any rash should be evaluated immediately; drug discontinuation is required unless the rash is clearly not drug-related. Patients should be closely monitored for signs of aseptic meningitis (headache, fever, nausea, stiff neck). Lamictal may cause hemophagocytic lymphohistiocytosis (HLH), a serious immune system reaction. It can also lead to blood dyscrasias (e.g., leukopenia, anemia), necessitating periodic blood monitoring in at-risk patients. Suicidal ideation and behavior have been reported with antiepileptic drugs; patients should be monitored for emergence or worsening of depression or suicidal thoughts. Caution is advised in patients with cardiac, hepatic, or renal impairment, as clearance may be reduced. Abrupt withdrawal may increase seizure frequency.
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 lamotrigine, unless the rash was unequivocally not drug-related.
Possible side effect
Common side effects (≥5% incidence) include: dizziness, headache, somnolence, insomnia, nausea, vomiting, diarrhea, dyspepsia, abdominal pain, rhinitis, pharyngitis, cough, rash, blurred or double vision, ataxia, coordination problems, and fatigue.
Serious but less common side effects require immediate medical attention. These include: serious skin rashes (SJS, TEN, Drug Reaction with Eosinophilia and Systemic Symptoms - DRESS), aseptic meningitis, hemophagocytic lymphohistiocytosis (HLH), blood abnormalities (e.g., neutropenia, agranulocytosis, anemia), multiorgan failure, suicidal thoughts or behaviors, and worsening of seizures. Patients should be instructed to report any new or worsening symptoms promptly.
Drug interaction
Lamictal undergoes significant pharmacokinetic interactions due to its metabolism by glucuronidation. Valproate inhibits lamotrigine metabolism, more than doubling its plasma levels; Lamictal doses must be reduced by approximately 50% when co-administered. Conversely, enzyme-inducing drugs like carbamazepine, phenytoin, phenobarbital, primidone, and rifampin can increase lamotrigine metabolism, reducing its plasma levels by ~40%; Lamictal doses may need to be increased. Oral estrogen-containing contraceptives can decrease lamotrigine plasma concentrations by approximately 50%; dose adjustments may be necessary during the pill-free week and upon starting or stopping such contraceptives. Lamictal itself may slightly reduce the exposure of levonorgestrel. Caution is advised when combining with other CNS depressants due to additive sedative effects.
Missed dose
If a dose of Lamictal 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 never take a double dose to make up for a missed one, as this increases the risk of side effects. Maintaining a consistent daily schedule is crucial for stable plasma levels and therapeutic efficacy.
Overdose
Overdose with Lamictal may present with signs of increased dose-dependent adverse effects. Reported symptoms include nystagmus, ataxia, impaired coordination, increased seizures, decreased level of consciousness, coma, and intraventricular conduction delay (QRS prolongation). Management is supportive and symptomatic; there is no specific antidote. Gastric lavage may be considered if presented early. Hemodialysis may be of limited benefit due to Lamictal’s moderate (55%) protein binding and volume of distribution, but it can be considered in severe cases. Cardiac monitoring is recommended following a large overdose.
Storage
Lamictal tablets should be stored at room temperature, between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). The medication must be kept in its original container, tightly closed, and protected from light and moisture. It should be stored out of reach of children and pets to prevent accidental ingestion. Do not store in bathrooms or other areas prone to dampness. Properly discard any expired or unused medication.
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 available scientific literature and prescribing information but may not be exhaustive or fully current.
Reviews
“As a consulting psychiatrist specializing in treatment-resistant mood disorders, Lamictal has been a cornerstone of my maintenance therapy strategy for over a decade. Its efficacy in preventing depressive relapse in bipolar I is superior to many alternatives, and the weight-neutral profile is a significant advantage for long-term patient adherence and metabolic health. The mandatory slow titration is a clinical necessity, not an inconvenience.” — Dr. Evelyn Reed, MD, Psychiatry
“From a neurological perspective, lamotrigine’s value extends beyond its FDA indications. I find it particularly useful in patients with epilepsy and comorbid mood instability, offering dual benefits. Its favorable cognitive side effect profile makes it a preferred choice for patients who cannot tolerate the sedative effects of other AEDs. The interaction with valproate requires vigilant management, but this is a well-characterized pharmacokinetic challenge.” — Dr. Ben Carter, DO, Neurology
“The risk of SJS, while serious, must be viewed in the context of appropriate prescribing practices. In 15 years of clinical use, adhering strictly to the recommended titration schedule, I have not encountered a single case. This medication has allowed countless of my patients to achieve stability without the burden of significant weight gain or sedation, dramatically improving their quality of life.” — Dr. Sarah Chen, MD, Psychopharmacology