Lamotrigine (Lamictal)

Class

Anticonvulsant, mood stabilizer

Mechanism

Inhibits voltage-gated sodium channels, stabilizing neuronal membranes and modulating glutamate release, which contributes to anticonvulsant and mood-stabilizing effects.

FDA-Approved Use

Epilepsy, bipolar disorder (maintenance)

Off-Label Use

Trigeminal neuralgia, cluster and migraine headaches, posttraumatic stress disorder (PTSD), hallucinogen persisting perception disorder, post-stroke aggression

Formulation

Tablets, chewable tablets, extended-release tablets

Titration

25 mg p.o. daily for 2 weeks, then gradual titration to reduce risk of rash; slower titration needed when combined with valproate, faster titration if used with hepatic enzyme inducers (e.g., carbamazepine)

Dose Range

100–200 mg/day (higher in some epilepsy protocols)

Kinetics

Half-life ~25 hours; metabolized primarily via glucuronidation; interaction with valproate increases serum levels and half-life

Common AEs

Dizziness, headache, nausea, blurred vision, ataxia, insomnia, benign rash

Serious/Rare AEs

Stevens-Johnson syndrome, toxic epidermal necrolysis, especially with rapid titration or valproate co-administration

Monitoring

Monitor for rash and signs of hypersensitivity; adjust dose for hepatic impairment and concomitant medications

Black Box Warning

Serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis

Considerations

Lamotrigine is effective in seizure populations and often preferred due to favorable metabolic profile and mood stabilization without weight gain. In elderly patients or those with dementia, slow titration is recommended to minimize dizziness and ataxia risk. Dose adjustments may be necessary in hepatic impairment, especially with valproate use. Lamotrigine may also improve mood and behavioral symptoms in individuals with developmental disabilities, particularly those with seizure comorbidity or bipolar disorder features, but careful titration and monitoring for rash is essential.