Tiagabine therapy for complex partial seizures. A dose-frequency study. The Tiagabine Study Group

Arch Neurol. 1997 May;54(5):595-601. doi: 10.1001/archneur.1997.00550170069016.


Objective: To evaluate the efficacy and safety of 2 regimens of tiagabine as add-on therapy for patients with complex partial seizures (CPSs) that are refractory to other treatment.

Design: Randomized, double-blind, placebo-controlled, add-on, parallel-group trial with an 8-week baseline period, 12-week experimental period (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week termination period.

Setting: Twenty-six centers throughout the United States.

Patients: Three hundred fifty-one patients were enrolled, 318 were entered in the double-blind period, and 271 completed the study.

Interventions: Tiagabine, 16 mg 2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the fixed dose.

Main outcome measure: The median change in the 4-week rate of CPSs from baseline to experimental period.

Results: The median change from baseline was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2 times per day, and it was -1.2 CPSs in the group of patients who were given tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the patients who were given tiagabine 2 times per day and in 27% of the patients who were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P < or = .001 for each tiagabine-treated group compared with the placebo group). The most frequent adverse events involved the central nervous system and occurred in comparable proportions in the 3 treatment groups. Similar proportions of patients discontinued the study prematurely for adverse events.

Conclusions: Tiagabine administered 2 and 4 times daily as add-on pharmacotherapy was effective in reducing CPSs in patients with epilepsy whose conditions were refractory to treatment with other antiepileptic agents, and it was well tolerated.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / therapeutic use*
  • Child
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Epilepsy, Complex Partial / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nipecotic Acids / administration & dosage
  • Nipecotic Acids / adverse effects
  • Nipecotic Acids / therapeutic use*
  • Retreatment
  • Tiagabine
  • Treatment Outcome


  • Anticonvulsants
  • Nipecotic Acids
  • Tiagabine