Gabapentin as add-on therapy for refractory partial epilepsy: results of five placebo-controlled trials.
Gabapentin (GBP, Neurontin), a new antiepileptic drug (AED) with a novel mechanism of action, exhibits low acute toxicity in mice, rats, and monkeys, and is not teratogenic. GBP pharmacokinetics are simple and predictable; GBP is eliminated by urinary excretion, is not protein-bound or metabolized, does not induce or inhibit hepatic enzymes, and does not interact with other AEDs. In five placebo-controlled, double-blind studies of GBP as add-on therapy, 307 patients with refractory partial seizures received placebo and 485 received GBP dosages of 600, 900, 1,200, or 1,800 mg/day for 12 weeks following a 12-week baseline. Seizure frequency, as measured by response ratio and responder rate, was improved for patients receiving GBP compared with placebo; differences were statistically significant in two of the three large, multicenter studies. Adverse events occurred in 76% of GBP-treated patients, compared with 57% of placebo-treated patients. No serious adverse events were consistently attributable to GBP therapy. Changes in clinical laboratory values were not considered clinically important. GBP represents a significant addition to the armamentarium of AEDs available for treatment of patients with epilepsy.
Parke-Davis Pharmaceutical Research, Division of the Warner-Lambert Company, Ann Arbor 48105.
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D000085:Acetates / Q000627:therapeutic use*; D000588:Amines; D000927:Anticonvulsants / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D016001:Confidence Intervals; D003509:Cyclohexanecarboxylic Acids; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015507:Drugs, Investigational / Q000627:therapeutic use; D004828:Epilepsies, Partial / Q000188:drug therapy*; D000077206:Gabapentin; D006801:Humans; D015337:Multicenter Studies as Topic; D010919:Placebos; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D015507:Drugs, Investigational; D010919:Placebos; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin