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

Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on seizure stage, afterdischarge (AD), and seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on amygdala-kindled seizures. The implications of these results for clinical therapeutics remain to be evaluated.
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PMID:Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam. 1073 34

Lamotrigine (Lamictal, Glaxo Wellcome) is a drug which is used as add-on therapy in patients with refractory epilepsy. Several previous studies have demonstrated the efficacy of lamotrigine monotherapy, but only few have been done in pediatric patients. The aim of our study was the assessment of efficacy and tolerability of lamotrigine monotherapy in children with newly diagnosed partial epilepsy. Lamictal was used in 19 children (11 boys and 8 girls), aged 3-16 years. 17 patients demonstrated complex partial seizures (with or without secondarily generalisation), 2 children had simplex partial seizures. Symptomatic epilepsy was diagnosed in 10 patients and cryptogenic epilepsy in 9 cases. The drug was administered at the dose of 3.87 +/- 1.02 mg/kg/day during 24 weeks. Three children withdrew from the study because of adverse events: one patient developed rash, two ones seizure exacerbation. Lamictal produced of at least 50% reduction in seizure frequency in 12 (63.15%) children, included 10 seizure-free patients. One third patients experienced EEG improvement. The most common adverse effects were gastrointestinal and sleep disturbances, infections, dizziness, all of them were mild and transient and observed more often in children under 12 years of age. Lamotrigine monotherapy is effective and safe for treatment of newly diagnosed cryptogenic and symptomatic epilepsy with partial seizures but further studies are necessary specially in young children.
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PMID:[The use of lamotrigine monotherapy in children with newly diagnosed partial epilepsy]. 1076 53

Lamotrigine (LTG) and Vigabatrin (VGB) has been licensed widely as adjunctive therapy for partial and secondary generalized seizures. We compared the efficiency of Lamotrigine and Vigabatrin as adjuvant therapy for 33 patients (16 male and 17 female) with drug-resistant partial epileptic seizures (simple and complex) with secondary generalization receiving combination therapy (carbamazepine--CBZ and valproic acid--VPA). Patients were enrolled if they had experienced two partial seizures (simple or complex) and one secondary generalization/month, despite combination therapy. Neurologic evaluation including CT, MRI and EEG was performed every 3 months during observation. Blood specimens for CBZ and VPA plasma concentration were obtained prior to the first LTG or VGB dose and twice a year during the treatment. The assessment of LTG and VGB effectiveness was performed in 2-month intervals during 2-3 years for vigabatrin (mean daily dose 2.0 g) and 1-2 years for Lamotrigine (mean daily dose 0.3 g). The treatment (CBZ, VPA or both) with Vigabatrin or Lamotrigine as adjunctive therapy was effective in about a half of patients with refractory epilepsy. Findings suggest that the reduction in partial seizures (simple or complex) frequency with Vigabatrin is greater than that with Lamotrigine. On the other hand, Lamotrigine seems to be more effective in patients with partial epileptic seizures with secondary generalization.
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PMID:[Lamotrigine versus vigabatrin as an add-on therapy in refractory epilepsy: prospective study]. 1076 56

Lamotrigine is a novel anticonvulsant, which has proven to be effective both as add-on and monotherapy. 13 studies have demonstrated efficacy in 1096 children with a variety of seizure types. Tolerability information in these studies was collected in a standard fashion, where investigators reported all adverse events regardless of the perceived relationship to the test therapies. Generally, lamotrigine treatment in these clinical trials was generally given at higher initial doses and faster dose escalations than are currently recommended. Most adverse events associated with lamotrigine were mild to moderate in severity and did not result in discontinuation of treatment. Results from placebo-controlled, add-on trials showed that 85% of lamotrigine recipients experienced an adverse event compared with 83% of placebo recipients. Lamotrigine was associated with an increased risk of adverse events in the nervous system (dizziness, tremor, ataxia, and diplopia), gastrointestinal tract (nausea), and urinary tract (infection). The incidence of most adverse events was lower among lamotrigine recipients in monotherapy trials than in add-on trials, suggesting that concurrent anticonvulsant treatment or drug interactions can be confounding risk factors above that of lamotrigine treatment alone. Skin rash associated with hospitalisation and the discontinuation of study drug was reported more frequently by lamotrigine recipients than by placebo recipients and more frequently by children than by adults. The simultaneous use of valproic acid (sodium valproate) was associated with an increased incidence of rash. Lamotrigine, an effective broad spectrum anticonvulsant, is well tolerated in children. The qualitative features of adverse events that occur with lamotrigine treatment are similar for children and adults. The incidence of rash may be reduced with proper initial dosing and dose escalation.
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PMID:The tolerability of lamotrigine in children. 1123 19

We investigated the rate of penetration into and the intra-relationship between the serum, cerebrospinal fluid (CSF) and regional brain extracellular fluid (bECF) compartments following systemic administration of lamotrigine in rat. The serum pharmacokinetics were biphasic with an initial distribution phase, (half-life approximately 3 h), and then a prolonged elimination phase of over 30 h. The serum pharmacokinetics were linear over the range 10 - 40 mg kg(-1). Using direct sampling of CSF with concomitant serum sampling, the calculated penetration half-time into CSF was 0.42+/-0.15 h. At equilibrium, the CSF to total serum concentration ratio (0.61+/-0.02) was greater than the free to total serum concentration (0.39+/-0.01). Using in vivo recovery corrected microdialysis sampling in frontal cortex and hippocampus with concomitant serum sampling, the calculated penetration half-time of lamotrigine into bECF, 0.51+/-0.11 h, was similar to that for CSF and was not area or dose dependent. At equilibrium, the bECF to total serum concentration ratio (0.40+/-0.04) was similar to the free to total serum concentration (0.39+/-0.01), and did not differ between hippocampus and frontal cortex. The species specific serum kinetics can explain the prolonged action of lamotrigine in rat seizure models. Lamotrigine has a relatively slow penetration into both CSF and bECF compartments compared with antiepileptic drugs used in acute seizures. Furthermore, the free serum drug concentration is not the sole contributor to the CSF compartment, and the CSF concentration is an overestimate of the bECF concentration of lamotrigine.
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PMID:Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigine. 1080 60

After a short historical review of the development of the pharmaceutical treatment of the epilepsies the author reviews some of the possible strategies to manage patients with the different types of epilepsies and epileptic syndromes using the classical drugs. A strategy used by most of the physicians uses Sodium Valproate as the first line drug for almost all patients. This may be replaced by other drugs according to their efficacy against the different types of seizures to be treated whenever VPA has not enough efficacy or isn t well tolerated. On the other hand epileptologists use the different drugs according to the different epilepsies and epileptic syndromes depending on the relative efficacy of each drug available and the possible side effects. He then describes succinctly the better-known new drugs and makes some comments on the coming drugs now in development. Finally he proceeds to include them in the strategies above described. Lamotrigine and possibly Topiramate are good candidates to replace VPA in the one drug strategy. Lamotrigine, Oxcarbamazepine and possibly Gabapentin may be used in the future as 1st line drugs in selected patients. Vigabatrin is already used as one of the better alternatives for West syndrome and Oxcarbamazepine has replaced Carbamazepine in countries where it s available to the public. Some drawbacks have been apparent with these drugs like the hepatic and haematological toxic effect of Felbamate or the apparently irreversible fields constriction provoked by Vigabatrin, which did limit their use.
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PMID:The new drugs and the strategies to manage epilepsy. 1082 13

During the past few years, a number of drugs have been added to the anti-epileptic arsenal. This review focusses on five of these drugs which have undergone extensive trials: Vigabatrin, Lamotrigine, Gabapentin, Felbamate and Oxcarbazepine. Some of these antiepileptic drugs appear to be helpful for treatment of catastrophic childhood epilepsies. Vigabatrin appears promising in children with infantile spasms who do not respond to ACTH or Prednisolone. Children with Lennox-Gastaut syndrome may respond to treatment with Lamotrigine or Vigabatrin. Gabapentin and vigabatrin have proved to be effective in refractory partial seizures. Oxcarbazepine, a ketoderivative of carbamazepine, is as effective as Carbamazepine but has a better safety profile. Lesser neurotoxicity and fewer drug interactions is another advantage with these drugs. However monitoring is required to determine the long term safety with their usage. These drugs have a definite role in childhood epilepsies refractory to conventional antiepileptic drugs.
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PMID:Newer anti-epileptic drugs. 1082 95

The paper evaluates the efficacy of the newer anticonvulsant lamotrigine in a developmentally disabled patient population. A retrospective evaluation was done at two institutional centres to assess adjunctive lamotrigine (Lamictal) efficacy in a developmentally disabled population. Mean seizure frequency was compared between a 2-month pre-lamotrigine baseline period and a 2-month treatment period. A 3-month lamotrigine titration phase occurred between baseline and treatment periods. Seizure frequency data was obtained from standardized, daily seizure records. Adverse effect data was obtained from medical and nursing notes. An intent to treat analysis was performed. Data were analysed using Student's t-test for paired data. We evaluated 44 centre residents (25 male, 19 female, average age 33 +/- 11 years). Mean lamotrigine dose was 272 +/- 133 mg per day. A significant reduction in seizure frequency was noted. Seizure frequency (all seizures) was 10.1 +/- 11.2 during the baseline period vs. 5.8 +/- 7.9 seizures per month during the treatment period (P = 0.002). Thirty-two percent of patients (n = 14) had greater than a 75% reduction in seizure frequency. Twenty-three percent of patients (n = 10) had a 50-74% seizure reduction. Twenty-five percent of patients (n = 11) had less than a 50% reduction in seizures, while 20% (n = 9) had an increase in seizures. A significant reduction of 48% in generalized seizures (9.5 +/- 11.6 vs. 4.9 +/- 6.5 seizures per month, P = 0.013) was noted. Reductions in partial seizure frequency of 48% (7.9 +/- 10 vs. 4 +/- 6.6 seizures per month, P = 0.16) as well as in mixed-type seizures (19.9 +/- 9.3 was vs. 15 +/- 12.1 seizures per month, P = 0.11) were also seen; however, these changes did not reach significance. Overall, lamotrigine was well tolerated by the subject population. Adjunctive treatment with lamotrigine appears to be an efficacious and well-tolerated treatment for seizures in a significant percentage of developmentally disabled patients with epilepsy.
Seizure 2000 Mar
PMID:Efficacy of lamotrigine in institutionalized, developmentally disabled patients with epilepsy: a retrospective evaluation. 1084 38

The authors presented the results of treatment with lamotrigine (LTG, Lamictal) in 13 patients with drug resistant epilepsy (add-on therapy). There were 8f, 5m. aged 16-60 years, mean age 28.8 years. Generalized seizures occurred in 8 patients (62%). In this group there was 1 patient (aged 16 years) with the Lennox-Gastaut syndrome and 1 patient (aged 20 years) with valproate resistant juvenile myoclonic epilepsy. Complex partial seizures and complex partial with secondary generalization occurred in 5 patients (38%). Before LTG addition mean seizure frequency was from 3/month to several times/day. The mean duration of epilepsy was 16.6 years. The 8 patients were treated with CBZ and VPA, one with PHT and VPA, one CBZ and VGB. Monotherapy with VPA was introduced in 3 patients. After 6 months of treatment with LTG the efficacy was evaluated. 12 patients took LTG with VPA, 1 LTG with CBZ. Complete reduction of seizures was achieved in 3 cases (23%), at least 50% reduction in 3 patients (23%), reduction below 50% in 4 patients (31%). In 3 cases (23%) the results of treatment were negative (increase or no change in seizure frequency). Beneficial psychotropic effect was observed in 9 patients (69%). Adverse effects occurred in 2 patients (15%). Headache, vertigo, sleepness were observed in one case. Rash occurred in 1 patient (treated with LTG and VPA). After 6 months 3 patients were excluded from the study because of negative effects of treatment. LTG is helpful and well tolerated in drug-resistant epilepsy.
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PMID:[Lamotrigine in add-on therapy: assessment of efficacy in drug resistant epilepsy]. 1084 3

A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to vigabatrin, such as encephalopathy, aphasia and motor disturbances. Vigabatrin-induced visual field constriction is the latest and most worrying ADR. Many questions regarding the nature of this potentially serious ADR remain unanswered, as no prospective controlled study examining the phenomenon has been published. Rare cases of behavioural ADRs and IgA and IgG2 deficiency associated with the use of zonisamide have been reported. However, relatively few patients so far have been exposed to this drug, and therefore more postmarketing information is required. The relatively late establishment of aplastic anaemia and hepatic failure as potentially fatal ADRs of felbamate, and of visual field constriction with vigabatrin, should serve as ample reminders that ADRs can appear at any time.
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PMID:Adverse reactions to new anticonvulsant drugs. 1091 31


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