Lamotrigine (Lamictal)
Mood stabilizer • Last reviewed 2025-09-23
General information
Lamotrigine (Lamictal) is an anticonvulsant approved for maintenance treatment of bipolar I disorder, preventing depressive episodes, and for focal and generalized seizures. It is not effective for acute mania but is valued for long-term prophylaxis with minimal metabolic side effects.
Formulations include immediate-release, orally disintegrating, chewable dispersible, and extended-release tablets ranging from 2 mg to 200 mg. Severe rash (including Stevens–Johnson syndrome) mandates a slow titration and patient education.
Common adverse effects: headache, dizziness, diplopia, nausea; rare but serious: aseptic meningitis, blood dyscrasias, rash.
Lamotrigine is valued for bipolar depression prevention and has minimal weight or prolactin effects, improving long-term adherence compared with many SGAs.
Dosing & administration
Bipolar maintenance (no valproate or enzyme inducers): 25 mg daily x2 weeks, 50 mg daily x2 weeks, 100 mg daily week 5, 200 mg daily by week 6.
With valproate: 25 mg every other day x2 weeks, 25 mg daily x2 weeks, 50 mg daily week 5, target 100 mg daily.
With enzyme inducers (carbamazepine, phenytoin, phenobarbital, primidone): start 50 mg daily x2 weeks, 100 mg daily x2 weeks, then increase by 100 mg/day weekly to 300–400 mg/day.
If off ≥5 half-lives (~5 days without valproate), restart titration schedule.
Target maintenance doses
- Monotherapy (no valproate/inducers)
- 200 mg/day
- With valproate
- 100 mg/day
- With enzyme inducers
- 300–400 mg/day
Mechanism of action
Lamotrigine inhibits voltage-sensitive sodium channels, stabilizing neuronal membranes and inhibiting glutamate release, which reduces excitatory transmission.
It may also modulate high-voltage calcium channels and has serotonergic effects that contribute to mood stabilization.
Metabolism & pharmacokinetics
Bioavailability ~98%; peak plasma concentrations 1–3 h after immediate-release dosing (8–12 h for XR).
Metabolized primarily via hepatic glucuronidation (UGT1A4, UGT2B7). Half-life ~25 h alone, reduced to 13–15 h with enzyme inducers and increased to 48–60 h with valproate.
About 94% excreted in urine (metabolites); 2% in feces. Protein binding ~55%.
Drug interactions
Valproate doubles lamotrigine concentrations; halve dose.
Enzyme inducers (carbamazepine, phenytoin, phenobarbital, primidone) reduce levels; increase dose.
Estrogen-containing contraceptives lower lamotrigine during active pills and increase during placebo; monitor mood and adjust.
Rifampin and lopinavir/ritonavir reduce exposure.
| Mechanism | Agents / factors | Management |
|---|---|---|
| UGT inhibition | Valproate | Reduce lamotrigine dose by 50% |
| UGT induction | Carbamazepine, phenytoin | Increase dose; monitor levels/symptoms |
| Hormonal contraception | Ethinyl estradiol | Monitor mood; adjust lamotrigine during cycle |
Monitoring & safety checks
Dermatologic exam / rash counseling
Baseline and each visit during titration • Risk of SJS/TEN
Liver function
Baseline and as indicated • Rare hepatic injury
Preconception/prenatal • Adjust dosing; clearance increases
Drug interaction review
Each visit • Adjust for valproate, inducers, contraceptives
Educate patients to stop therapy at first sign of rash unless clearly benign.
Therapeutic drug monitoring (2.5–15 mcg/mL) can aid in adherence or toxicity questions.
Discontinuation guidance
Taper over ≥2 weeks to reduce risk of seizures or mood destabilization.
If rash occurs, discontinue immediately and avoid rechallenge unless benefits outweigh risks.
Special populations
Pregnancy: clearance increases substantially; dose adjustments often required each trimester.
Renal impairment: no major adjustment, but monitor for accumulation in ESRD.
Adverse effects
Common: headache, dizziness, diplopia, nausea, tremor.
Serious: SJS/TEN, aseptic meningitis, blood dyscrasias.
References
- Lamictal (lamotrigine) — Prescribing Information — FDA/GSK (2023)
- Lamotrigine in bipolar disorder — Depression and Anxiety (2002) DOI: 10.1002/da.10030
- Safety of lamotrigine — CNS Drugs (2016) DOI: 10.1007/s40263-016-0350-y
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.