Lamotrigine (Lamictal)


Clinical Information

HALF-LIFE: 25-33 hours
   If taken with Valproic acid: 48-70 hours
   If taken with Carbamazepine: 13-14 hours

METABOLISM: Liver, but not via CYP450 system

STARTING DOSE: 25mg PO daily

TARGET DOSING RANGE: 50mg-200mg per day

BEST TIME TO DOSE: Any (causes insomnia in some patients)


If dosing without valproic acid:
>Initial 25mg PO Daily for two weeks
>Increase to 25mg PO BID for two weeks
>Increase to 50mg PO BID for two weeks
>If tolerated, can consolidate to once daily dosing
>Max dose without valproate typically 200mg per day


If dosing with valproic acid:
>Initial 25mg PO every other day for two weeks
>Increase to 25mg PO daily for two weeks then 50mg PO daily
>Max dose with valproate typically 100mg per day



PREGNANCY: Minimal data on safety in humans. Must weigh risk of discontinuing vs risk of teratogenicity (which is low)

BREASTFEEDING: Minimal data on safety in humans. Recommend bottle/formula feeding

Side Effects

Rash (benign), Fatigue, Insomnia, vivid dreams, headache, nausea, worsening of acne, worsening of psoriasis, upset stomach, diarrhea, hyponatremia, DRESS Syndrome, Steven-Johnson’s Syndrome/TEN (EXTREMELY RARE).

Important Drug-Drug Interactions

Valproic acid (Depakote, Divalproex) + Lamotrigine (Lamictal): Valproic acid inhibits lamotrigine metabolism. Dose of lamotrigine must be decreased by half the normal dose when given in combination with valproic acid.

Hormonal contraceptives + Lamotrigine (Lamictal): Hormonal Contraceptives may decrease Lamotrigine levels. Caution during contraceptive-free “pill-free” periods as lamotrigine levels may rise substantially.

Hormonal contraceptives + Lamotrigine (Lamictal): Lamotrigine may decrease levels of hormonal contraceptives

Carbamazepine (Tegretol) + Lamotrigine (Lamictal):  Carbamazepine (Tegretol) decreases lamotrigine levels

FDA Indications

  1. Bipolar Disorder (maintenance/preventing mood episodes)
  2. Seizures in adults and children

Off Label Uses: Bipolar Depression, Mixed states, Rapid Cycling Bipolar Disorder, Borderline Personality Disorder

Mechanism(s) of Action

  • Inhibits Voltage Gated Sodium Channels
  • Lamotrigine has been shown to reduce glutamate release and modulate reuptake of monoamines including serotonin and dopamine

Additional Information

  • Lamotrigine shows prophylactic and antidepressant properties, but is no better than placebo in treating mania
  • Lamotrigine has been shown to increase the time between both depressive and manic episodes
  • May be a good add-on medication with lithium for bipolar depression
  • Rash associated with rapid dose escalation. Reduce dose and slow titration if benign rash develops



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