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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progress made in the development of new antiepileptics (AEs) is justified by the high percentage of refractory patients to the available medical therapy (25%), although only a minority of cases are deemed suitable for surgical therapy. Yet, the ideal AE, that is, with a well-known mechanism of action, effective in monotherapy for all epileptic fits, with a perfect pharmacokinetic profile, with no adverse or teratogenic effects, with no drug interactions and available under many formulations, is far from being developed. The new AEs arise either from modification of already marked drug molecules or clinical formulations or from the effectiveness on the excitatory/inhibitory balance of the major neurotransmitters involved in the pathogenesis of seizures, the gamma-amino-butyric acid (GABA) as the inhibitory, and the glutamate (GLU) as the excitatory one. However, the mechanism remains unknown in a few of them. Those new AEs already marketed in Portugal (Vigabatrin), soon to be (Lamotrigine, Oxcarbazepine) or available abroad only (Gabapentin, Zonisamide) are review with special emphasis on their pharmacokinetic profile, side effects, interaction with other AEs, and clinical use. In conclusion, these new drugs have brought a very important advancement in the management of refractory patients, but the development of well-designed comparative trials involving both monotherapy and polytherapy has become important in order to develop useful strategies in the drug management of epilepsy.
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PMID:[New antiepileptic medications]. 774 11

Gabapentin (GBP) has shown antiepileptic efficacy and good tolerance in clinical trials. Much remains to be learned about its clinical use. As a participating center in the US Gabapentin Study Group, we report observations that have practical implications for patient management. Twenty-three patients with intractable partial-onset seizures initiated open-label treatment after a blinded placebo-controlled add-on dose efficacy study. In the titration phase, GBP and concurrent antiepileptic drugs (AEDs) were adjusted to achieve optimal efficacy on maximally tolerated GBP doses. Nine patients had no significant improvement in seizure control and discontinued GBP. The remaining 14 patients were observed while treated long-term with stable-dose GBP and concurrent AEDs. Improvement was maintained as long as patients were followed: < or = 4 years. The protocol-allowed upper dose limit, 2,400 mg/day, was well tolerated by 16 of 23 patients, indicating that higher doses may be tolerated. GBP discontinuation did not cause rebound increases in seizure frequency. The most common adverse events (AEs) (in 14 of 23) were similar to those induced by concurrent AEDs and responded to reduction of concurrent AEDs. Many patients reported positive psychostimulatory effects. These observations extend previous findings indicating that GBP is an effective and well-tolerated drug for treatment of partial-onset seizures.
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PMID:Efficacy and tolerance of long-term, high-dose gabapentin: additional observations. 792 48

For the first time in 15 years, new antiepileptic medications are available for the treatment of patients with seizure disorders. These drugs have demonstrated efficacy in animal models of epilepsy and in controlled clinical trials. Felbamate was licensed in 1993 for use as adjunctive therapy or monotherapy in adults with partial or tonic-clonic seizures and as adjunctive therapy for children with the Lennox-Gastaut syndrome. Gabapentin was approved January 1994 as adjunctive therapy in patients 12 years or older with partial seizures, with or without secondary generalization. Lamotrigine is expected to be approved this year for the treatment of partial and tonic-clonic seizures in adults. Last, a new drug application has been filed for vigabatrin this year, with possible licensing next year. These four anticonvulsants present new options in the treatment of patients with refractory epilepsy and are not merely congeners of previously available treatments. They have unique clinical spectrums and are reported to be safer and better tolerated than conventional therapy. Trials to compare their use with that of conventional therapy have not been done, and their use in the initial treatment of patients with epilepsy is not completely clear.
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PMID:Guidelines for treating epilepsy in the age of felbamate, vigabatrin, lamotrigine, and gabapentin. 797 72

The challenges of treating patients with partial seizures soon will be met, in part, by a number of new additions (felbamate, gabapentin, lamotrigine) to existing treatment options. Gabapentin, has shown significant promise in the treatment of patients with refractory partial seizures and secondarily generalized tonic-clonic seizures. Three large, randomized, multicenter, double-blind, placebo-controlled, parallel-group clinical trials have established its efficacy and safety as add-on therapy in patients with refractory partial seizures. Gabapentin is well tolerated. Although adverse events occur in most patients receiving gabapentin as adjunctive therapy, they are transient and mild to moderate in severity. To date, serious adverse events have been rare. Long-term safety data are needed. The lack of drug interaction potential between gabapentin and traditional antiepileptic drugs also was confirmed in clinical trials.
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PMID:Clinical efficacy and safety of gabapentin. 802 37

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.
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PMID:Gabapentin as add-on therapy for refractory partial epilepsy: results of five placebo-controlled trials. 803 75

Gabapentin (GBP, Neurontin) is a novel antiepileptic drug (AED) that was shown to be effective against refractory partial seizures in five placebo-controlled trials. However, a number of patients with complex partial seizures experienced an increase in seizure frequency, suggesting that patients suffering from complex partial seizures are not a homogeneous group. In fact, we found that currently available AEDs are likely to be ineffective when staring is a prominent component of complex partial seizures. The poor response of this group of patients may reflect the fact that staring spells are inhibitory seizures and that the AEDs prescribed for partial seizures appear to facilitate inhibitory mechanisms. GBP resembles phenytoin (PHT) and carbamazepine (CBZ) in depressing segmental and reticular excitatory mechanisms and facilitating segmental inhibitory mechanisms, just as it resembles PHT and CBZ in efficacy against some partial seizures and against secondarily generalized seizures. Perhaps the patients in whom GBP increased seizure frequency had complex partial seizures with staring and were therefore unlikely to benefit from drugs such as GBP, CBZ, and PHT, which enhance inhibitory mechanisms in the brain. These findings suggest that future AED trials would greatly benefit from a categorization of complex partial seizures into nosologically distinct groups.
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PMID:Gabapentin: discussion. 803 76

A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mg/day group provided dose-response data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with > or = 50% reduction in seizure frequency), and response ratio, where RRatio = (T-B)/(T + B). Median PCH was -21.8% in the 900-mg/day group and -17.8% in the 1,200-mg/day group as compared with -0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean RRatio was -0.136 in the 900-mg/day group and -0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,200-mg/day than for the 900-mg/day group (RRatio = -0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group. 808 24

This is the 2-year interim report of results from a multicenter, open-label study evaluating the long-term efficacy and safety of gabapentin (Neurontin) as add-on therapy in patients with refractory partial seizures who had had a therapeutic response to gabapentin in a preceding 12-week double-blind trial or 12-week open-label extension. A total of 240 patients continued to receive gabapentin as add-on therapy at dosages of 600-2400 mg/day for an average of 342 days (range 10-784 days). Efficacy analyses compared seizure frequency during consecutive 12-week treatment periods with seizure frequency during the 12-week baseline. During the nine treatment periods evaluated, the percent of patients with a 50% or greater reduction in seizure frequency ranged from 35% to 71%, and the median percent change in seizure frequency ranged from -33% to -60%. At the time of data cutoff, 30% of patients had withdrawn from the study due to lack of efficacy, and 4% due to adverse events. In 225 patient-years of gabapentin treatment in this study, CNS adverse events reported by more than 10% of patients were nystagmus, somnolence, diplopia, tremor, ataxia, and dizziness. No consistent changes in clinical laboratory values were associated with gabapentin. Gabapentin as add-on therapy at dosages up to 2400 mg/day is safe during long-term treatment in patients with refractory partial seizures. Subgroup analyses of patients who remained in the study over the long term confirmed that gabapentin maintained efficacy for up to 2 years.
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PMID:The long-term safety and efficacy of gabapentin (Neurontin) as add-on therapy in drug-resistant partial epilepsy. The US Gabapentin Study Group. 808 58

Gabapentin, administered as add-on therapy, was safe and effective in this 12-week, multicenter, placebo-controlled, parallel-group study in 306 patients with refractory partial epilepsy. For patients in each gabapentin treatment group (600, 1,200, or 1,800 mg/d), the mean response ratio was significantly better than that of a placebo group. The percentage of patients achieving at least a 50% reduction in seizure frequency was 8% among placebo-treated patients and ranged from 18% to 26% for patients who received gabapentin. Adverse events were generally mild and transient and occurred at a slightly higher frequency among patients receiving gabapentin than among those receiving placebo. Gabapentin did not affect the serum concentrations of concurrent antiepileptic drugs and was not regularly associated with any deviations in clinical laboratory values. Gabapentin's low inherent toxicity and its lack of drug interactions make it an ideal candidate for use as add-on therapy in patients with refractory partial epilepsy.
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PMID:Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. The US Gabapentin Study Group No. 5. 823 45

Three new antiepileptic drugs (AEDs) are likely to be approved in the United States by the Food and Drug Administration in the near future. In general, all three have good safety profiles, causing only mild, well-tolerated side effects. Felbamate (FBM) is effective in the treatment of partial seizures and Lennox-Gastaut epilepsy. FBM appears to have a broader spectrum of antiepileptic activity than carbamazepine (CBZ) or phenytoin (PHT). Gabapentin (GBP) was designed to be a structured analogue of gamma-aminobutyric acid (GABA). GBP is most effective in the maximal electroshock model of seizures but may have a different mechanism of action than CBZ and PHT. Unique pharmacokinetic properties (no hepatic metabolism and no protein binding) may make GBP especially useful for certain patients, such as those with hepatic disease and elderly patients who are receiving multiple medications. The overall profile of activity of lamotrigine (LTG) is similar to that of PHT and may act on voltage-sensitive sodium channels to stabilize neuronal membranes. LTG is effective in partial seizures, and there is some indication that LTG may be helpful in primary generalized seizures. The long half-life and lack of effect on other AEDs will make LTG easy to dose and add to a patient's existing regimen. These new agents will provide physicians with more effective medications from which to choose in the treatment of the patient with epilepsy.
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PMID:Advances in the pharmacotherapy of epilepsy. 833 15


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