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

The efficacy of gabapentin (Neurontin), in generalized seizures was evaluated in this 14 week, double-blind, placebo-controlled, parallel-group, add-on, multicenter study. A total of 129 patients with refractory generalized seizures were randomized to receive either placebo or 1200 mg/day gabapentin as add-on therapy. Patients received their standard regimens of antiepileptic drugs (AEDs) during a 12 week baseline period, and gabapentin or placebo was added-on in the subsequent 14 week evaluation period. Results of both an intent-to-treat (ITT) and evaluable-patient analyses showed that gabapentin provided greater reduction in the frequency of generalized tonic-clonic seizures than did placebo; however, the differences between treatments were not statistically significant. Gabapentin did not affect the frequency of absence or myoclonic seizures. Adverse events were reported by 67% of gabapentin-treated patients and by 56% of placebo-treated patients. The most frequently occurring adverse events among patients receiving gabapentin were somnolence, fatigue, and dizziness. Gabapentin is well tolerated by patients with generalized seizures. The results of this study show a trend toward an effect of gabapentin in reducing the frequency of generalized tonic-clonic seizures and suggest that further exploration of high dose gabapentin in generalized epilepsy is warranted.
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PMID:Gabapentin in generalized seizures. 895 16

Gabapentin is a novel anti-epileptic drug which enhances GABA (gamma-aminobutyric acid) turnover in certain brain regions, including substantia nigra. However, the functional consequences of GABA turnover increases in response to gabapentin and their potential involvement in the anticonvulsant action of this drug are not known. In the present study, we examined the effects of gabapentin on the extracellular, single unit activity of nondopaminergic (presumably GABAergic) neurons of the substantia nigra pars reticulata in rats. During the recordings, the animals were infused with the narcotic opioid analgesic fentanyl, associated with a skeletal muscle relaxant and artificial ventilation. The spontaneous firing of substantia nigra pars reticulata neurons was determined up to about 2 h after i.v. or i.p. administration of gabapentin at doses of 15-30 mg/kg. After both routes of administration, gabapentin markedly reduced neuronal firing when administered at a dose of 20-30 mg/kg, while 15 mg/kg were ineffective in this regard. The suppressive effect of gabapentin was rapid in onset (2 min after i.v. and about 20 min after i.p. injection), reached peak values of about 70% below predrug baseline after about 45-60 min, and remained at this level for at least 2 h. Vehicle administration had no effect on substantia nigra pars reticulata neurons. The ability of gabapentin to alter substantia nigra pars reticulata firing does correlate with its known ability to increase nigral GABA turnover. Since a substantial body of evidence suggests that the substantia nigra pars reticulata is a critical site at which decrease of neuronal firing by potentiation of GABAergic influences results in protection against various seizure types, the suppressive effect of gabapentin on substantia nigra pars reticulata activity may contribute to the anticonvulsant action of this drug.
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PMID:The anticonvulsant gabapentin decreases firing rates of substantia nigra pars reticulata neurons. 898 88

Efficacy and safety of gabapentin monotherapy were evaluated in 33 children with newly diagnosed absence epilepsy in two identical, double-blind, placebo-controlled trials in which a 2-week double-blind treatment phase was followed by a 6-week open-label phase. Primary efficacy criterion was seizure frequency change from baseline to end of double-blind treatment derived from quantified electroencephalograms. Primary efficacy analyses compared treatment differences in the 2-week double-blind phase. Gabapentin did not significantly decrease or increase seizure frequency compared with placebo. Low dosages with possibly subtherapeutic plasma levels may have contributed to the lack of demonstrable efficacy. Somnolence and dizziness were the only adverse events reported by at least two patients during gabapentin treatment. No clinically important changes in laboratory assessments or other safety parameters were observed. Gabapentin monotherapy at dosages ranging from 9.7 through 19.1 mg/kg/day is well tolerated in pediatric patients aged 4 through 12 years with absence epilepsy.
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PMID:Gabapentin in naive childhood absence epilepsy: results from two double-blind, placebo-controlled, multicenter studies. 912 Feb 26

Epilepsy is a common condition in people with learning disabilities with many patients continuing to suffer from seizures despite antiepileptic drug (AED) treatment. Although the advent of newer AEDs offers hope for better treatment, there is a need to compare the efficacy of each new AED in adults with both drug-resistant epilepsy and learning disabilities. This retrospective casenote study involves the analysis of the outcome for those adults with learning disabilities treated with either vigabatrin, lamotrigine or gabapentin. The information obtained from the casenote analysis was used to both compare the efficacies of the three drugs and also the side-effects and drop-out rates, including reasons for drop-out. The total number of patients involved was 51 who underwent 71 treatment episodes. All three AEDs had similar efficacies. Although vigabatrin was found to be associated with a higher incidence of behaviour problems, behaviour problems occurred with the other drugs as well. Lamotrigine caused increased seizures in 24% of patients, especially when prescribed at a higher dose. Gabapentin appeared to be associated with fewer serious side-effects.
Seizure 1997 Apr
PMID:A naturalistic study of the use of vigabatrin, lamotrigine and gabapentin in adults with learning disabilities. 915 25

The therapeutic options for the treatment of epilepsy have expanded during the 1990s. Since 1993, four novel agents (felbamate, gabapentin, lamotrigine, and topiramate) have been approved by the US Food and Drug Administration, primarily for adjunctive treatment of partial seizures. In addition, a water-soluble pro-drug of phenytoin, fosphenytoin, and a sustained-release preparation of carbamazepine have been introduced. The novel anticonvulsants represent a potential improvement for patients whose seizures are incompletely controlled or who experience significant adverse effects with older anticonvulsants. Felbamate, lamotrigine, and topiramate appear to have a broad spectrum of action in seizure control, but felbamate use is limited by the potential for serious adverse effects. Gabapentin, lamotrigine, and topiramate are all well tolerated. Gabapentin has no known drug interactions, whereas lamotrigine and topiramate have limited interactions compared with older agents. The sustained-release preparation of carbamazepine may decrease the incidence of adverse effects and increase patient compliance. Fosphenytoin offers a safer method for intravenous administration of phenytoin and the added flexibility of intramuscular administration. Taken together, these recent advances in treatment may bring about improved efficacy and decreased adverse effects for many patients with epilepsy.
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PMID:Recent advances in the pharmacotherapy of epilepsy. 922 Feb 4

Several new antiepileptic drugs have become available recently. Since seizures and epilepsy are common, primary care physicians are likely to encounter a patient who is taking one of these new medications. Successful medical management of epilepsy requires a proper understanding of medication half-life, indications, and side effects. Felbamate has a broad spectrum of efficacy but is limited by side effects and idiosyncratic reactions. Fosphenytoin has the efficacy of phenytoin and offers the advantage of intramuscular and intravenous dosing without the significant adverse effects associated with intravenous phenytoin; however, it is expensive. Gabapentin has minimal side effects and drug interactions yet has limited efficacy for seizures. Lamotrigine has broad seizure efficacy but requires a slow adjustment to therapeutic levels. Topiramate has minimal drug interactions, but therapy must be initiated slowly to avoid side effects. All of the new antiepileptics hold great promise in the management of patients with recurrent seizures.
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PMID:New antiepileptic drugs. Overcoming the limitations of traditional therapy. 922 84

Tiagabine is a novel antiepileptic drug which has clinical efficacy against complex refractory and myoclonic seizures. The anticonvulsant mechanism of action of tiagabine results from its blockade of neuronal and glial GABA-uptake, thereby increasing GABA levels in the synaptic cleft. Here we present a comparison of the preclinical anticonvulsant profile of tiagabine with that of lamotrigine, gabapentin and vigabatrin in the following tests (all antiepileptic drugs were administered i.p.): seizures induced by pentylentetrazol (PTZ), 6,7-dimethoxy-4-ethyl-b-carboline-3-carboxylate (DMCM) and maximal electroshock (MES); sound induced seizures in DBA/2 mice and finally acute amygdala kindled seizures. Tiagabine was the most potent drug in antagonizing tonic convulsions induced by PTZ, DMCM and sound induced seizures in DBA/2 mice with ED50 values of 2, 2 and 1 mumol/kg, respectively, followed by lamotrigine with ED50 values of 9, 43 and 6 mumol/kg, respectively. Gabapentin and vigabatrin had ED50 values in the same tests of 185, 452, 66 mumol/kg and 2322, > 7740, 3883 mumol/kg, respectively. Tiagabine was the only drug capable of blocking PTZ-induced clonic convulsions (ED50 = 5 mumol/kg), an effect seen at low but not high doses of tiagabine. Lamotrigine was the only drug which antagonized tonic convulsions in the MES test (ED50 = 36 mumol/kg). Therapeutic index (TI) of antiepileptic drugs in NMRI- and DBA/2-mice ranked with decreasing TI lamotrigine > gabapentin > vigabatrin > tiagabine. All drugs reduced the generalized seizures in amygdala kindled rats, but tiagabine and gabapentin furthermore attenuated afterdischarge duration of amygdala kindled seizures. However, an ED50 value against amygdala kindled focal seizures was only obtained for tiagabine (36 mumol/kg). The data here presented show that tiagabine, lamotrigine, gabapentin and vigabatrin possess different preclinical anticonvulsant profiles which is of relevance to the clinical anticonvulsant profiles of the drugs.
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PMID:Comparison of the preclinical anticonvulsant profiles of tiagabine, lamotrigine, gabapentin and vigabatrin. 925

The authors reviewed changes in body weight in 44 patients treated with Gabapentin (GPN) for a period of 12 or more months. All patients had a seizure disorder and the dose of GPN was increased aiming at complete seizure control or until side effects limited further increase. Twenty-eight patients were receiving GPN dosages of > 3000 mg/day. Observed changes in body weight were as follows 10 patients gained more than 10% of their baseline weight, 15 patients gained 5% to 10% of baseline, 16 patients had no change, and 3 patients lost 5% to 10% of their initial weight. Weight increase started between the second and the third months of GPN treatment in most patients and tended to stabilize after 6 to 9 months of treatment, although the doses of GPN remained unchanged. Weight gain occurred in patients taking GPN in combination with each of the major antiepileptic drugs including Felbatol and also occurred with GPN monotherapy.
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PMID:Changes in body weight with chronic, high-dose gabapentin therapy. 926 79

We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures.
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PMID:Gabapentin monotherapy: I. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 88/89. 930 34

Gabapentin is a recently introduced antiepileptic drug for the treatment of partial seizures. Although studied extensively in adults, there have been few pediatric studies. It is a unique drug because it has no protein binding, is not metabolized, and is excreted through the kidneys. There are no significant drug interactions with other antiepileptic drugs nor do other antiepileptic drugs alter the pharmacokinetics of gabapentin. The drug is effective in partial seizures, although most studies have used the drug as add-on therapy. It is approved for use of partial seizures with or without secondary generalization in patients over the age of 12 years. The side effect profile of the drug is quite good. No significant idiosyncratic reactions have been reported. The most common side effects have included dizziness, fatigue, and headache. Rarely, children will have adverse behavioral effects, such as hyperactivity and agitated behavior. Usually these children have pre-existing behavioral disturbances. Although the spectrum of efficacy of gabapentin remains to be determined, it is likely to have a major beneficial impact on the treatment of childhood epilepsy.
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PMID:Gabapentin for treatment of epilepsy in children. 932 92


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