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

Data from five almost identical protocols have been pooled to give the results of treatment with lamotrigine in 285 children with refractory epilepsy. All the children received lamotrigine as open, add-on therapy and efficacy was assessed after the first 12 weeks of maintenance dosage. More than 50% reduction in seizures was achieved for over 30% of patients with complex partial, secondary generalized tonic-clonic, myoclonic, primary generalized tonic-clonic and atonic seizures; and, more than 50% of those with typical or atypical absences. In children treated for more than a year, there was no evidence of development of tolerance. Evaluations by investigators and parents found lamotrigine to improve the child globally in 74% of cases. Lamotrigine was well tolerated. Dizziness, unsteadiness and other non-specific side-effects that have been noted in a small minority of adults were rarely complained of by children. Rash was the most frequently reported side effect, leading to withdrawal of the drug in 7.4% of patients. However, the rate was lower when lamotrigine dosage was increased slowly as recommended. Data from other, smaller trials have also been reviewed and it is concluded that lamotrigine is a very well tolerated drug with a broad spectrum of efficacy.
Seizure 1994 Dec
PMID:Lamotrigine--a clinical overview. 789 52

Childhood epilepsy presents many different challenges requiring a careful assessment and an individual management plan appropriate to the needs of each child. The first rule in managing the difficult-to-treat patient is to re-examine the diagnosis. The characterization of the seizures may also guide the clinician into prescribing the appropriate therapy. If the child has failed to respond to first-line antiepileptic drugs, the situation should be reviewed carefully. There may be a role for one of the new antiepileptic drugs. It is important to treat with adequate doses and for adequate duration before deciding whether a drug is effective or not. Failure to do this may deny the child the benefit of a particular medication. Drugs which affect behaviour or cause lethargy can have a secondary effect on cognition. Failure to treat frequent subtle seizures may also have serious cognitive consequences. Lamotrigine is of value in treating a variety of different seizure types, including subtle seizures, and has a low incidence of adverse effects.
Seizure 1994 Dec
PMID:Lamotrigine--managing the challenging patient. 789 54

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

We prospectively monitored our experience of lamotrigine as add-on therapy in 45 patients with refractory epilepsy. Nine patients (20%) withdrew from treatment due to adverse drug reactions and five patients (11%) withdrew because of a deterioration in seizure frequency. A further 17 patients (38%) showed little (< 25%) reduction in seizure number, eight patients (18%) showed a 25-50% reduction whilst 15 patients (33%) had a 50% or greater reduction in seizure number (P = 0.002). Lamotrigine was of greater benefit in patients with tonic-clonic seizures (seven of fourteen [50%] showed a > 50% seizure reduction; P = 0.01) than in patients with complex partial seizures (seven of 22 [32%] showed a > 50% seizure reduction; P = 0.02). Despite a high withdrawal rate due to ADRs, lamotrigine proved of significant benefit to one-third of our study group.
Seizure 1994 Sep
PMID:Impact of lamotrigine on patients with refractory epilepsy: the Leicester experience. 800 Jul 15

No new antiepileptic drugs (AEDs) were licensed in the United States from 1978 to 1992. In late 1992, felbamate and gabapentin were recommended for approval, and in early 1993, lamotrigine. In July 1993, felbamate was licensed, and gabapentin and lamotrigine may soon follow. Lamotrigine, vigabatrin and clobazam are in use outside the US. Tiagabine, oxcarbazepine, fosphenytoin, topiramate, vigabatrin and zonisamide are in Phase II clinical testing in the US. All of the new AEDs are effective against partial and tonic-clonic seizures. Few controlled clinical trials have been done in patients with absence and myoclonic seizures. Mechanisms of action of the new drugs have not been clearly defined. The new AEDs will provide an opportunity to improve the care of epileptic patients. Even with optimal management with currently available drugs, some 30% of patients remain refractory to medical management.
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PMID:How about the new antiepileptic drugs? 800 Sep 69

Lamotrigine (LTG) is a chemically novel antiepileptic drug (AED) that blocks voltage-sensitive sodium channels, leading to inhibition of neurotransmitter release, principally glutamate. LTG is active in a wide range of pharmacologic models of epilepsy, demonstrating a potency and duration of action generally superior to currently available AEDs. Preliminary evidence of efficacy was provided by single-dose studies showing effects on reducing interictal spike activity and photoconvulsive response. A total of eight randomized, double-blind, placebo-controlled, crossover trials have established the efficacy of LTG in patients with refractory partial epilepsy. Literature reports suggest LTG also is effective in patients with idiopathic generalized epilepsy, including absence seizures, and in patients with Lennox-Gastaut syndrome. Other reports suggest that LTG is useful in the pediatric population, and an interim report of an open monotherapy trial suggests that the efficacy of LTG was comparable to that of carbamazepine (CBZ) but the adverse experiences leading to discontinuation were less frequent.
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PMID:Lamotrigine: a review of antiepileptic efficacy. 803 68

Fourteen children (6 M, 8 F) suffering from refractory epilepsy received LTG as add-on therapy. LTG was administered twice daily at dosages increasing up to 2 mg/kg/day (for patients taking VPA) or to 10 mg/kg/day for patients taking AEDs that induce hepatic metabolism. The drug was withdrawn for side effects in 3 cases (rash: two cases, hirsutism: one), because of increased seizure frequency in 2 cases and because of unchanged seizure frequency in one. One patient died from acute respiratory failure, after repeated respiratory tract infections. A decrease in seizure frequency after one year of treatment with LTG was observed in 6 of the 7 patients who completed the study. The median total seizure frequency decreased from 10.7 +/- 7.3 to 3.8 +/- 4.6 seizures per day. At the end of the study, seizure frequency had decreased by more than 50% in 2 patients, by more than 75% in 2 patients, and 2 patients were seizure-free; in the remaining patient seizure frequency was unchanged. The best results were obtained with plasma LTG concentrations ranging from 0.5 to 5.4 micrograms/ml; no further improvement was observed at higher LTG concentrations.
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PMID:Lamotrigine in resistant childhood epilepsy. 813 79

An elevated CSF glutamate level has recently been reported in Rett syndrome. Because the anticonvulsant effect of Lamotrigine is probably due to inhibition of glutamate release, this drug was given as an add-on drug to 4 girls with Rett syndrome. All patients responded with a seizure reduction of 50% or more and an improved well-being. A controlled study at the early stages of the syndrome could be interesting.
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PMID:Lamotrigine in Rett syndrome. 813 81

We evaluated the efficacy and safety of lamotrigine (300 and 500 mg/day) as add-on therapy in a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of 216 patients with refractory partial seizures. During 6 months of treatment, median seizure frequency decreased by 8% with placebo, 20% with 300 mg lamotrigine, and 36% with 500 mg lamotrigine. Seizure frequency decreased by > or = 50% in one-third of the 500-mg group and one-fifth of the 300-mg group. Reductions in seizure frequency and seizure days were statistically significant, compared with placebo, for the 500-mg group but not the 300-mg group. Most adverse events were minor and resolved over time. Nine percent of patients on lamotrigine withdrew because of adverse experiences. Lamotrigine plasma concentrations appeared to be a linear function of dose, and the drug did not affect plasma concentrations of concomitant antiepileptic drugs. Lamotrigine was safe, effective, and well tolerated as add-on therapy for refractory partial seizures.
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PMID:Placebo-controlled study of the efficacy and safety of lamotrigine in patients with partial seizures. U.S. Lamotrigine Protocol 0.5 Clinical Trial Group. 823 44

Lamotrigine is an antiepileptic agent which blocks voltage-dependent sodium channels, thereby preventing excitatory neurotransmitter release. Clinical evidence indicates that lamotrigine is effective against partial and secondarily generalised tonic-clonic seizures, as well as idiopathic (primary) generalised epilepsy. As monotherapy, lamotrigine 100 to 300 mg/day has similar medium term (30 to 48 weeks) efficacy to carbamazepine 300 to 1400 mg/day and phenytoin 300 mg/day against partial onset seizures and idiopathic generalised tonic-clonic seizures in adults with newly diagnosed epilepsy, and appears to be better tolerated than the older agents. As adjunctive therapy, lamotrigine (50 to 500 mg/day) has shown efficacy in short term ( < or = 6-months) placebo-controlled studies in adults with refractory partial epilepsy, reducing total seizure frequency (by < or = 60%) and producing improvement ( > or = 50% reduction in seizure frequency) in < or = 67% of patients. Both simple and complex partial seizures and secondarily generalised tonic-clonic seizures are reduced by lamotrigine, with generalised seizures (particularly absence seizures, atonic seizures and Lennox-Gastaut syndrome) tending to be more responsive than partial seizures. This reduction in seizure frequency is sustained on long term ( < or = 3 years) therapy and is reportedly accompanied by an improvement in psychological well-being. In children with refractory multiple seizure types, lamotrigine ( < or = 15 mg/kg/day; 400 mg/day) has proved effective as add-on therapy, with approximately equal to 40% of patients showing > or = 50% reductions in seizure frequency and approximately equal to 10 % achieving abolition of seizures after 3 months' treatment. Generalised seizures, including atypical and typical absence seizures, atonic and tonic seizures and Lennox-Gastaut syndrome are most responsive. The most common adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological. Maculopapular or erythematous skin rash, occasionally severe, occurs in approximately equal to 10% of patients and is the most common cause of treatment withdrawal. The risk of rash can, however, be minimised through adoption of a low, slow dosage titration schedule on initiating therapy. As monotherapy, lamotrigine produces less drowsiness than carbamazepine or phenytoin, and less asthenia and ataxia than phenytoin. Clinical experience would therefore suggest that lamotrigine is a particularly effective and generally well tolerated broad-spectrum agent for adjunctive treatment of both partial epilepsy and idiopathic generalised epilepsy in adults and children. Initial indications point to the drug filling an increasingly important future role in the monotherapy of newly diagnosed epilepsy.
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PMID:Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy. 853 54


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