Epilepsia
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Review Randomized Controlled Trial Multicenter Study Clinical Trial
Postherpetic neuralgia: role of gabapentin and other treatment modalities.
Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. ⋯ Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.
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Review Randomized Controlled Trial Clinical Trial
Monotherapy trials with gabapentin for partial epilepsy.
The efficacy and safety of gabapentin as monotherapy for treatment of partial onset seizures were evaluated in three large multicenter, double-blind, parallel-group, dose-controlled trials. In the first trial, 275 outpatients with refractory partial epilepsy maintained on stable doses of one or two antiepileptic drugs (AEDs) were switched to gabapentin (GBP) monotherapy at 600 mg, 1200 mg, or 2400 mg daily. Patients were required to exit the 26-week double-blind phase of the study if they experienced worsening of seizure frequency. ⋯ The completion rate for the CBZ group (37%) was similar to that of the GBP 900-mg (39%) and 1800-mg (38%) groups. Patients receiving CBZ had a higher withdrawal rate because of adverse events compared with the GBP 900-mg and 1800-mg groups. The results of these trials provide good evidence of the efficacy and safety of GBP as monotherapy for the treatment of partial-onset seizures.
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To determine whether neurochemical activation of the N-methyl-D-aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured as binding of 11C-labeled (S)-[N-methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE). ⋯ Radioactivity uptake of intravenously administered (S)-[N-methyl-11C]ketamine was reduced in temporal lobes of ictal in patients with TLE. This may reflect reduced NMDA-receptor density, reduced perfusion, focal atrophy, or other factors.
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Gabapentin (GBP) is a antiepileptic drug (AED) indicated as adjunct therapy for treatment of partial seizures, with and without secondary generalization, in patients 12 and older with epilepsy. GBP (1-(aminomethyl) cyclohexaneacetic acid) is structurally related to gamma-aminobutyric acid (GABA), which readily crosses the blood-brain barrier. Radiolabeled GBP binds throughout the central nervous system in anatomic areas important in treatment of seizures. ⋯ Although efficacy occurs at lower levels, increased GBP doses are associated with additional efficacy. Reports suggest that initiation at 2,400 mg or 3,600 mg may not be associated with increased adverse experiences. Titration to 900 or 1,200 mg on the first day of GBP therapy appear to be well tolerated.
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Review Comparative Study
Comparative anticonvulsant and mechanistic profile of the established and newer antiepileptic drugs.
Since 1993, several new antiepileptic drugs (AEDs) have been introduced for management of partial seizures. Like the established AEDs, the new drugs are believed to exert their anticonvulsant action through enhancement of inhibitory-mediated neurotransmission, or reduction of excitatory-mediated neurotransmission, or by a combination of both. Among the new drugs, vigabatrin (VGB) and tiagabine (TGB) are unique in that they were derived from mechanistic-based drug discovery programs designed to identify effective AEDs that inhibit the metabolism and reuptake of the inhibitory neurotransmitter GABA, respectively. ⋯ FBM and TPM differ from both the established and newer AEDs in their ability to modulate NMDA- and AMPA/kainate-mediated excitatory neurotransmission, respectively. The multiple mechanisms of action associated with FBM, TPM, ZNS, GBP, and perhaps LTG, and the unique modulation of GABA levels by VGB and TGB, are likely to account for the anticonvulsant efficacy of these newer AEDs in patients with epilepsy. For each of the new drugs, their proposed mechanisms of action are discussed in relationship to their preclinical and clinical anticonvulsant profiles.