GABAPENTIN - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND CLINICAL POTENTIAL IN EPILEPSY

Gabapentin is an antiepileptic drug with an unknown mechanism of actio n apparently dissimilar to that of other antiepileptic agents, and pos sessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminish ing the likelihood of drug interactions with other antiepileptic agent s and drugs such as oral contraceptives. Although gabapentin is a stru ctural analogue of the neurotransmitter gamma-aminobutyric acid (GABA) , which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with part ial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day.) provides notable benefit, reducing seizure freque ncy by greater-than-or-equal-to 50% in 18 to 28% of patients with refr actory partial seizures, as shown in 3 double-blind, placebo-controlle d trials. Overall, seizure frequency decreased by 18 to 32% during 3-m onth treatment periods. Patients with complex partial seizures, and pa rtial seizures secondarily generalised, are particularly likely to res pond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly s omnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated w hen administered to a few patients for periods of up to 5 years, its l ong term tolerability profile has yet to be fully expounded. Thus, wit h its favourable pharmacokinetic profile, and efficacy in some refract ory patients, gabapentin is poised to fill a niche as an adjunct to th e treatment of partial epilepsy. Promising results obtained thus far w arrant further work to clarify its long term tolerability, its possibl e efficacy in other seizure types, its position relative to other agen ts and its use as monotherapy. In the meantime, gabapentin is likely t o provide a much-needed option in a therapeutic area requiring complex management.