General Information

Neurontin (gabapentin) is an anticonvulsant used to control various types of seizures in the treatment of epilepsy. It has also been used with some success in other conditions, including post poliomyelitis pain and amyotrophic lateral sclerosis. It was recently approved as an adjunctive therapy (added to other antiepileptic drugs) for the treatment of partial seizures in pediatric patients, and was previously approved for the treatment of partial seizures with and without secondary generalization in adults with epilepsy.

Epilepsy is a brain disorder in which clusters of nerve cells, or neurons, in the brain sometimes signal abnormally. This disturbance of the normal pattern of neuronal activity can cause strange sensations, emotions, and behavior or sometimes convulsions, muscle spasms, and loss of consciousness.

Clinical Results

The effectiveness of Neurontin Capsules as adjunctive therapy was established in three multicenter placebo-controlled, double-blind, parallel-group trials in 705 adults with refractory partial seizures. Effectiveness was assessed primarily on the basis of the percent of patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the "responder rate") and a derived measure called response ratio.

One study compared Neurontin 1200 mg/day TID with placebo. The responder rate was 23% in the Neurontin group and 9% in the placebo group; the difference between groups was statistically significant. A second study compared primarily 1200 mg/day TID Neurontin with placebo, with additional Neurontin dosage groups (600 mg/day, 1800 mg/day) also studied for information regarding dose response. The responder rate was higher in the Neurontin 1200 mg/day group (16%) than in the placebo group (8%), but the difference was not statistically significant. The responder rate at 600 mg was also not significantly higher than in the placebo, but the rate in the 1800 mg group was statistically superior to the placebo rate. A third study compared Neurontin 900 mg/day TID and placebo. A statistically significant difference in responder rate was seen in the Neurontin 900 mg/day group (22%) compared to that in the placebo group (10%). (from FDA label for Neurontin Capsules)

Side Effects

Adverse events associated with the use of Neurontin in combination with other antiepileptic drugs include the following:

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• Dizziness
• Somnolence (drowsiness)
• Ataxia (loss of normal muscular coordination)
• Fatigue
• Nystagmus (rapid, involuntary to-and-fro movement of the eyes)

Mechanism of Action

The mechanism by which gabapentin exerts its anticonvulsant action is unknown, but in animal test systems designed to detect anticonvulsant activity, gabapentin prevents seizures as do other marketed anticonvulsants. Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does not interact with GABA receptors, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation.

Several test systems ordinarily used to assess activity at the N-methyl-D-aspartate (NMDA) receptor have been examined. Results are contradictory. Accordingly, no general statement about the effects, if any, of gabapentin at the NMDA receptor can be made.

In vitro studies with radiolabeled gabapentin have revealed a gabapentin binding site in areas of rat brain including the neocortex and hippocampus. The identity and function of this binding site remain to be elucidated. (from FDA label)

Additional Information

For additional information on epilepsy, please visit the web site of the Epilepsy Foundation, a national charitable organization dedicated to assisting those affected by the condition.