Lamotrigine (Lamictal)

HALF-LIFE: 25-33 hours
   >With valproic acid: 48-70 hours
   >With Carbamazepine: 13-14 hours

 

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

 

 

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

 

Additional Information

  • Lamotrigine shows prophylactic and antidepressant properties, but is no better than placebo in treating mania
  • Lamotrigine has been shown to reduce glutamate release and modulate reuptake of monoamines including serotonin and dopamine
  • 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
  • Mostly case reports and open labeled trials support lamotrigine in rapid cycling bipolar disorder, bipolar depression, and mixed episodes but RCTs have not consistently demonstrated efficacy for these conditions
  • Lamotrigine carries a risk of both benign rash and Steven Johnson’s Syndrome/TEN
  • Rash associated with rapid dose escalation
  • Reduce dose and slow titration if benign rash develops
  • Interaction between valproic acid and lamotrigine: Valproic acid inhibits lamotrigine metabolism; dose of lamotrigine must be decreased by half the normal dose when given in combination with valproic acid
  • Many hormonal contraceptives decrease lamotrigine levels – Caution during contraceptive-free “pill-free” periods as lamotrigine levels may rise substantially. Conversely, lamotrigine may decrease levels of hormonal contraceptives
  • Carbamazepine decreases lamotrigine levels
  • If lamotrigine stopped/missed for >5 half-lives then strongly consider restarting titration

References:

  1. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  2. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  3. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  4. 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.
  5. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  6. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  7. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  8. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  9. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.