GABA-mimetic — raises CNS GABA via GABA-T inhibition; also blocks voltage-gated Na+ channels and modulates Ca²⁺. Broad-spectrum antiseizure + bipolar + migraine prophylaxis. Strong CYP2C9 inhibitor + UGT inhibitor (raises lamotrigine 2×). Teratogenic (NTDs); mitochondrial toxicity in young children.
Half-Life (t½)
PO: 14h, IV: 14h
Dosing Guidelines
PO: Typical 1000 mg (Range: 250–2000 mg)
Target Organ Systems
nervous
digestive
Interactions
Lamotrigine (major): UGT1A4 inhibition. Anderson 1996 (PMID:8823232): valproate 500 mg BID approximately doubles lamotrigine half-life — start lamotrigine at 25 mg every other day, escalate slowly to mitigate SJS/TEN risk. Bidirectional: lamotrigine modestly raises valproate CL (small effect, opposite direction).
Phenytoin (warn): Clinical plasma-binding displacement. Riva 1984 (PMID:6430316) n=9 epileptic patients, before/after VPA add-on: "The mean free fraction rose from 0.135 +/- 0.019 (s.d.) to 0.182 +/- 0.030" — Δfu = 0.047/0.135 ≈ 0.35. Total PHT may look unchanged while free PHT (active drug) rises ~35% — TDM by free-PHT or symptoms, not total level.