Topiramate (Topamax)

Clinical Information:

HALF-LIFE: 19-25 hours
STARTING DOSE: 12.5mg-25mg per day
TARGET DOSING RANGE: 50mg-200mg per day
BEST TIME TO DOSE: Any
HOW TO DOSE:
> Initial 12.5mg-25mg per day
> Increase dose by 25mg per week
> For weight loss/prevent weight gain: 50mg-150mg/day
> For Mood effects: Usually 100mg-200mg per day in divided doses
> Max dose usually 400mg/day
PREGNANCY: Minimal data on safety.
BREASTFEEDING: Minimal date on safety.

 

FDA INDICATIONS:
1) Epilepsy
2) Prophylaxis of Migraine headaches

 

Topiramate has also been used off label for:

  • Antipsychotic-induced weight gain (usually 50mg-150mg daily)
  • Neuropathic pain
  • Borderline personality disorder
  • Alcohol use disorders
  • Cocaine use disorders

 

Mechanism(s) of Action:

  • Blocks voltage sensitive sodium channels
  • Inhibits glutamate release
  • Potentiates activity of GABA
  • Blocks calcium channels
  • Topiramate inhibits carbonic anhydrase (increased risk of metabolic acidosis and kidney stones)
  • Topiramate may have prophylactic properties, but appears to exert little benefit during acute bipolar depression or mania.

 

Side Effects:

  • Psychomotor slowing
  • Decreased concentration
  • Somnolence
  • Fatigue
  • Anorexia
  • Kidney stone formation
  • Cognitive side effects (“Dope-a-max” or topamax “fog”) most common reason for discontinuing

 

Additional Information:

  • Used in children with Lennox-Gastaut Syndrome
  • Carbamazepine increases elimination of topiramate
  • Topiramate may increase plasma levels of phenytoin
  • Topiramate is a weak inhibitor of CYP219
  • Topiramate is weak inducer of CYP3A4
  • Alcohol enhances sedation and may increase risk of seizures

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.