Topiramate
Topamax · Qsymia
AnticonvulsantGeneric availableTDM data
The precise mechanisms by which topiramate exerts its anticonvulsant and preventive migraine effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate's efficacy for epilepsy and the preventive treatment of migraine. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.
Compare Topiramate →FDA-Approved Indications
- Epilepsy — initial monotherapy (partial-onset or PGTC; 2+ years)
- Epilepsy — adjunctive (partial-onset, PGTC, Lennox-Gastaut; 2+ years)
- Migraine prophylaxis (12+ years)
Common Off-Label Uses
- Alcohol use disorder
- Binge eating disorder
- Bulimia nervosa
- PTSD
- Obesity (adjunct)
- Essential tremor
What Sets This Drug Apart
- Weight LOSS (not gain) is a distinctive side effect among psychotropics; FDA-approved in combination with phentermine for obesity (Qsymia)
- Cognitive impairment ('topiramate fog') is common and dose-dependent: word-finding difficulty, memory problems, and concentration deficits
- Carbonic anhydrase inhibition causes metabolic acidosis and increases nephrolithiasis (kidney stone) risk; adequate hydration recommended
- Paresthesia is the most common adverse effect (40% incidence — highest single-AE rate among all drugs in this tool)
- Teratogenic: FDA category D with evidence of oral clefts; effective contraception required in women of childbearing potential
- Off-label for bipolar mood stabilization, migraine prophylaxis, alcohol use disorder, and binge eating disorder