Contents
Clinical Information

HALF-LIFE: 25-33 hours
If taken with Valproic acid: 48-70 hours
If taken with Carbamazepine: 13-14 hoursMETABOLISM: 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)
HOW TO DOSE:
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
*RESTART TITRATION IF STOPPED/MISSED FOR >5 HALF LIVES*
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
- Bipolar Disorder (maintenance/preventing mood episodes)
- 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
VIDEO
References
- Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
- Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
- Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
- J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
- Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
- Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
- Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
- Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
- Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.