Tiagabine: efficacy and safety in adjunctive treatment of partial seizures.
OBJECTIVE
To assess the efficacy and safety of tiagabine (TGB), a new antiepileptic drug (AED), as add-on therapy in patients with refractory partial seizures.


METHODS
This response-dependent study used an open-label screening phase (in which patients were titrated to their optimal TGB dose, < or =64 mg/day) followed by a double-blind, placebo-controlled, crossover phase. Initial eligibility criteria included (a) seizures inadequately controlled by existing AEDs, and (b) six or more partial seizures during an 8-week baseline period. Patients showing benefit from TGB (> or =25% reduction in total seizure rate relative to baseline) were eligible for randomization into the double-blind phase, which comprised two 7-week assessment periods separated by a 3-week crossover period.


RESULTS
Forty-four (50%) of the 88 enrolled patients entered the double-blind phase of the study during which there were significant reductions compared with placebo in all partial (p < 0.01), complex partial (p < 0.001), and secondarily generalized tonic-clonic seizure rates (p < 0.05). Thirty-three percent of patients experienced a reduction of > or =50% in the all partial seizure rate. Eight (22%) patients receiving TGB during the double-blind phase reported adverse events, of which dizziness and incoordination were the most frequent. Three patients withdrew from treatment during the double-blind phase because of adverse events; two during treatment with TGB and one during treatment with placebo. TGB did not affect plasma concentrations of other coadministered AEDs.


CONCLUSIONS
TGB was significantly better than placebo in terms of seizure rate reduction and was generally well-tolerated in patients with difficult to control seizures.
Crawford
P
P
Bootham Park Hospital, York, England.
Meinardi
H
H
Brown
S
S
Rentmeester
T W
TW
Pedersen
B
B
Pedersen
P C
PC
Lassen
L C
LC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001007:Anxiety / Q000139:chemically induced; D001247:Asthenia / Q000139:chemically induced; D018592:Cross-Over Studies; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D010352:Patient Dropouts; D010919:Placebos; D000078308:Tiagabine; D016896:Treatment Outcome
D000927:Anticonvulsants; D009557:Nipecotic Acids; D010919:Placebos; D000078308:Tiagabine