Does Gabapentin Decrease Seizure Threshold?
No, gabapentin does not decrease seizure threshold—it is an anticonvulsant medication that raises the seizure threshold and is used specifically to prevent and control seizures.
Mechanism and Clinical Use
Gabapentin functions as an antiepileptic drug (AED) with anticonvulsant properties, meaning it actively works to prevent seizures rather than provoke them 1. The drug is FDA-approved as adjunctive therapy for partial seizures with or without secondary generalization in patients over 12 years of age 2, 1.
Evidence of Efficacy in Seizure Control
Gabapentin demonstrates clear efficacy in reducing seizure frequency when used as add-on therapy for drug-resistant partial epilepsy, with patients nearly twice as likely to achieve 50% or greater reduction in seizures compared to placebo (RR 1.89,95% CI 1.40 to 2.55) 3.
Dose-response analysis shows increasing seizure control with higher doses, with 25.3% of patients responding to 1800 mg daily compared to 9.7% on placebo—representing a 15.5% absolute increase in response rate 3.
Clinical practice data demonstrates that 72% of patients experienced greater than 50% reduction in seizures, with 23% achieving greater than 75% reduction when gabapentin was added to their regimen 4.
Safety Profile and Tolerability
Gabapentin has a broad therapeutic index and favorable safety profile, with no causal relationship established to life-threatening organ toxicity despite treatment of nearly 3 million patients 1.
Common adverse effects include somnolence, dizziness, ataxia, and fatigue (RR 1.93 to 2.43 compared to placebo), but these do not indicate seizure threshold lowering 2, 3.
The drug has minimal drug-drug interactions and is eliminated unchanged renally, making it a well-tolerated option for seizure management 1.
Clinical Dosing Considerations
Standard loading in the emergency department is 900 mg/day (300 mg three times daily) for 3 days, with no difference in seizure recurrence compared to slower loading 2.
Maintenance dosages of 3600 mg/day or higher are well-tolerated and provide superior seizure control compared to lower doses typically used in initial clinical trials 1, 5.
Pediatric dosing ranges from 23 to 78 mg/kg per day, with similar efficacy and tolerability profiles 5.
Important Clinical Distinction
A critical pitfall is confusing gabapentin with medications that actually DO lower seizure threshold. Tramadol, for example, explicitly reduces seizure threshold through its serotonergic mechanisms and should be avoided in patients with seizure history 6. Gabapentin has the opposite effect—it is protective against seizures and is specifically prescribed to prevent them 1, 3.