topiramate and Epilepsy--Tonic-Clonic

This is an updated version of the original Cochrane Review published in Issue 12, 2016. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line AED for individuals with newly diagnosed seizures is of great importance and should be based on the highest-quality evidence available regarding the potential benefits and harms of various treatments for an individual.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs.. To review the time to treatment failure, remission and first seizure with topiramate compared with carbamazepine when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform (ICTRP) to 22 May 2018. We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators.. Randomised controlled trials (RCTs) comparing monotherapy with either topiramate or carbamazepine in children or adults with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. This was an individual participant data (IPD), review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission, time to 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI.. IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and treatment failure outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results for the primary outcome, time to treatment failure, given as pooled HR adjusted for seizure type were: time to failure for any reason related to treatment 1.16 (95% CI 0.97 to 1.38); time to failure due to adverse events 1.02 (95% CI 0.82 to 1.27); and time to failure due to lack of efficacy 1.46 (95% CI 1.08 to 1.98). Overall results for secondary outcomes were time to first seizure 1.11 (95% CI 0.96 to 1.29); and time to six-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (95% CI 0.71 to 0.99).The results of this review are applicable mainly to individuals with focal onset seizures; 81% of individuals included within the analysis experienced seizures of this type at baseline. For individuals with focal onset seizures, a statistically significant advantage for carbamazepine was shown for time to failure for any reason related to treatment (HR 1.21, 95% CI 1.01 to 1.46), time to treatment failure due to lack of efficacy (HR 1.47, 95% CI 1.07 to 2.02), and time to 12-month remission (HR 0.82, 95% CI 0.69 to 0.99). There was no statistically significant difference between topiramate and carbamazepine for 'time to first seizure' and 'time to six-month remission'.Evidence for individuals with generalised tonic-clonic seizures (9% of participants contributing to the analysis), and unclassified seizure types (10% of participants contributing to the analysis) was very limited; no statistically significant differences were found but CIs were wide; therefore we cannot exclude an advantage to either drug, or a difference between drugs.The most commonly reported adverse events with both drugs were drowsiness or fatigue, "pins and needles" (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression. The rate of adverse events was similar across the two drugs.We judged the methodol. For individuals with focal onset seizures, there is moderate-certainty evidence that carbamazepine is less likely to be withdrawn and high-certainty evidence that 12-month remission will be achieved earlier than with topiramate. We did not find any differences between the drugs in terms of the other outcomes measured in the review and for individuals with generalised tonic-clonic seizures or unclassified epilepsy; however, we encourage caution in the interpretation of results including small numbers of participants with these seizure types.Future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Humans; Induction Chemotherapy; Male; Randomized Controlled Trials as Topic; Recurrence; Time Factors; Topiramate; Treatment Failure

Primary generalized tonic clonic seizures (pGTCS) are still linked to major concerns for the clinic and hazards for patients suffering from idiopathic generalized epilepsy (IGE), so a quick search of the most effective and appropriate therapy is needed to control them. The key criteria for proper treatment are syndromic diagnosis and distinction between newly diagnosed and refractory patients. Other criteria include age, gender and comorbidities. Areas covered: Treatment for pGTCS has expanded in the last two years, with new antiepileptic drugs like perampanel joining valproic acid, lamotrigine, levetiracetam, topiramate, while further evidence-based data are required for zonisamide and lacosamide. Expert opinion: Currently, valproic acid can be considered as a first choice in male or menopausal women, and in the absence of weight issue, both in adults and in children, and in the absence of side effects such as insomnia and headache. Today, valproic acid is not recommended in child-bearing age and in relation to possible cognitive problems, especially in children. Lamotrigine and levetiracetam can be a viable alternative as a first choice. Topiramate is also effective as a first choice, but concerns may arise from its potential cognitive and memory adverse side effects. Additionally, perampanel and lacosamide are promising treatments.

Topics: Acetamides; Anticonvulsants; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Isoxazoles; Lacosamide; Lamotrigine; Levetiracetam; Male; Nitriles; Piracetam; Pyridones; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Zonisamide

Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line antiepileptic therapy for individuals with newly diagnosed seizures is of great importance. It is important that the choice of AED for an individual is based on the highest-quality evidence available regarding the potential benefits and harms of various treatments. It is also important to compare the efficacy and tolerability of AEDs appropriate to given seizure types.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs.. To assess the effects of topiramate monotherapy versus carbamazepine monotherapy for epilepsy in people with partial-onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. We searched the Cochrane Epilepsy Group Specialized Register (14 April 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2016) and MEDLINE (Ovid, 1946 to 14 April 2016). We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators.. Randomised controlled trials in children or adults with partial-onset seizures or generalised-onset tonic-clonic seizures with or without other generalised seizure types with a comparison of monotherapy with either topiramate or carbamazepine.. This was an individual participant data (IPD) review. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to first seizure post randomisation', 'time to 6-month remission, 'time to 12-month remission' and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and used the generic inverse variance method to obtain the overall pooled HRs and 95% CIs.. IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and withdrawal outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results, given as pooled HR adjusted for seizure type (95% CI) were: for time to withdrawal of allocated treatment 1.16 (0.98 to 1.38); time to first seizure 1.11 (0.96 to 1.29); and time to 6-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (0.71 to 1.00).The results of this review are applicable mainly to individuals with partial-onset seizures; 85% of included individuals experienced seizures of this type at baseline. For individuals with partial-onset seizures, a statistically significant advantage for carbamazepine was shown for time to withdrawal of allocated treatment (HR 1.20, 95% CI 1.00 to 1.45) and time to 12-month remission (HR 0.84, 95% CI 0.71 to 1.00). No statistically significant differences were apparent between the drugs for other outcomes and for the limited number of individuals with generalised-onset tonic-clonic seizures with or without other generalised seizure types or unclassified seizures.The most commonly reported adverse events with both drugs were drowsiness or fatigue, 'pins and needles' (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression The rate of adverse events was similar across the two drugs.We judged the methodological quality of the included trials generally to be good; however, there was some evidence that the open-label design of the larger of the two trials may have influenced the withdrawal rate from the trial. Hence, we judged the evidence for the primary outcome of treatment withdrawal to be moderate for individuals with partial-onset seizures and low for individuals with generalised-onset seizures. For efficacy outcomes (first seizure, remission), we judged the evidence from this review to be high for individuals with partial-onset seizures and moderate for individuals with generalised-onset or unclassified seizures.. For individuals with partial-onset seizures, there is evidence that carbamazepine is less likely to be withdrawn and that 12-month remission will be achieved earlier than with topiramate. No differences were found between the drugs in terms of the outcomes measured in the review for individuals with generalised tonic-clonic seizures with or without other seizure types or unclassified epilepsy; however, we encourage caution in the interpretation of these results due to the small numbers of participants with these seizure types.We recommend that future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.

Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Humans; Induction Chemotherapy; Topiramate

Occurrence of generalized tonic-clonic seizures (GTCS) is one of the most important risk factors of seizure-related complications and comorbidities in patients with epilepsy. Their prevention is therefore an important aspect of therapeutic management both in idiopathic generalized epilepsies and in focal epilepsies.. It has been shown that the efficacy of antiepileptic drugs (AEDs) varies across epilepsy syndromes, with some AEDs efficacious against focal seizures with secondary GTCS (sGTCS) but aggravating primary GTCS (pGTCS). In patients with pGTCS, evidence-based data support the preferential use of valproic acid, lamotrigine, levetiracetam and topiramate. In patients with sGTCS, all AEDs approved in the treatment of focal epilepsies might be used.. Both in pGTCS and sGTCS, additional data are required, specifically to inform about the relative efficacy of AEDs in relation to each other. Although valproic acid might be the most efficacious drug in idiopathic generalized epilepsies, it should be avoided in women of childbearing age due to its safety profile. In patients with sGTCS, AEDs for which the impact on this seizure type has been formally evaluated and which have demonstrated greater efficacy than placebo might preferentially be used, such as lacosamide, perampanel and topiramate.

Topics: Acetamides; Anticonvulsants; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Humans; Lacosamide; Lamotrigine; Levetiracetam; Piracetam; Risk Factors; Seizures; Topiramate; Treatment Failure; Triazines; Valproic Acid

Anti-epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE.. This was a non-randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument.. Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05).. For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.

Topics: Adolescent; Adult; Anticonvulsants; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Psychometrics; Taiwan; Topiramate; Young Adult

The aim of this study was to evaluate the efficacy and tolerability of topiramate (TPM) in juvenile myoclonic epilepsy (JME).. We assessed seizure control and adverse effects of TPM in 22 patients (18 females) aged 13 to 53 years. Target TPM dosage was up to 200 mg/day. The patients were subdivided into 3 groups: those treated with seizure control plus side effects (n=4); treated with non-controlled seizures (n=15) and with JME newly diagnosed (n=3).. Sixteen patients completed the first year of the follow-up. Generalized tonic-clonic seizures were completely controlled in 10 (62.5%); more than 50% of reduction in 4 (25.0%) and less than 50% in 2 (12.5%). Myoclonia were controlled in 11 (68.8%) and persisted in 5 (31.2%) patients. Absence seizures were present in 5 (22.7%) of whom 2 (9.0%) showed more than 50% of seizure reduction while 3 (13.6%) presented worsening. Discontinuations were due to inadequate seizure control and adverse events (N=4), low compliance and loss of follow-up (N=2) and subject choice (N=1).. TPM showed to be an effective and well-tolerated drug in the treatment of JME. Although frequently observed, TPM side effects were tolerable and the drug could be maintained in the majority of patients.

Topics: Adolescent; Adult; Anticonvulsants; Diagnostic and Statistical Manual of Mental Disorders; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Myoclonic Epilepsy, Juvenile; Prospective Studies; Topiramate; Treatment Outcome

Topiramate is an effective treatment for several types of seizures. The aim of this study is to assess the efficacy and tolerability of slow topiramate dose titration as add-on therapy in childhood epilepsy. This investigation is a prospective open-label, single-center, add-on study in 22 children with a diagnosis of refractory epilepsy. Topiramate (dose 0.5-2 mg/kg/day) was titrated at 2-week intervals up to the recommended dose of 6-12 mg/kg/day. Seizure frequency rate reduction was significant, declining from 23 +/- 5.1 seizures/week (mean +/- S.E.M.) at baseline phase to 3.5 +/- 1.2 seizures/week at the end of the 16-week stabilization phase (P < 0.001). After 16 weeks of stabilization, 19 patients (86%) had more than 50% seizure reduction. Seven patients (31%) were 100% seizure-free. Two patients (9%) manifested no improvement; only one patient (5%) did not tolerate the added drug and discontinued topiramate. One patient manifested severe side effects, whereas 21 patients experienced mild to moderate side effects mostly represented by somnolence, nervousness, and anorexia with or without weight loss. We conclude that slow dose titration improves efficacy and tolerability of topiramate as add-on therapy in the treatment in refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Epilepsy; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Infant; Male; Prospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

Intensive and quantitative evaluation of the duration, intensity and frequency of tonic and clonic signs of secondarily generalized tonic-clonic seizures (GTCS) in patients with pharmacoresistant partial seizures during topiramate (TPM) treatment.. Thirty patients suffering from refractory partial seizures with secondarily GTCS undergoing presurgical evaluation were randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg daily) group of TPM add-on medication (15 patients for each group). Study phases included a 3 days baseline video-EEG phase, a 10 days TPM titration phase without video-EEG and a 3 days TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured for each recorded secondarily generalized tonic and clonic signs: duration (lasting seconds), intensity (on a 0-3 scale), frequency (numbers per 24 h).. A total of 46 complex partial seizures with secondarily generalized tonic-clonic signs during the baseline phase and 20 during the dose maintenance phase were intensively analyzed. More patients in the medium dosage group than in the low dosage groups were free from secondarily GTCS during the dose maintenance phase (nine vs. two, P<0.05). Intergroup comparison suggested that the duration of all tonic signs decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P<0.05). There were statistically more significant reductions in the duration and intensity of clonic signs in the medium dosage group (P<0.05).. TPM has an early dose-dependant effect on secondarily GTCS in patients with pharmacoresistant partial seizures.. The present study intensively analyzed the duration, intensity, and frequency of secondarily generalized tonic and clonic signs in patients with pharmacoresistant partial seizures. The quantitative data suggested that TPM had a robust early inhibitory effect on secondarily generalized tonic-clonic signs; effects were more prominent in the medium dosage group (200 mg daily) than in the low dosage group (100 mg daily).

Topics: Adolescent; Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Middle Aged; Topiramate; Treatment Outcome

A total of 131 adults and children (mean age, 27 years; range, 3-59 years) with generalized tonic-clonic seizures (GTCS) of nonfocal origin resistant to other antiepileptic drugs (AEDs) were treated with open-label topiramate (TPM) after completing double-blind placebo-controlled trials.. The mean duration of open-label TPM treatment was 387 days (range, 14-909 days); the mean TPM dose was 7 mg/kg/day (range, 1-16 mg/kg/day). At the last study visit, the frequency of GTCS was reduced > or =50% from baseline in 63% of patients and by > or =75% in 44%. Among patients treated > or =6 months, 16% were GTCS free > or =6 months despite a pretreatment seizure frequency of one GTCS/week (median). Treatment with TPM was being continued in 82% of patients (n = 107) at the last visit. During treatment periods of up to 2.5 years, 11 (8%) patients discontinued TPM because of adverse events and seven (5%) because of inadequate seizure control.. TPM therapy was well tolerated, and seizure control was maintained with long-term, open-label therapy in patients with GTCS, leading to prolonged seizure-free intervals in some patients with seizures previously resistant to AED therapy.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Middle Aged; Patient Dropouts; Placebos; Topiramate; Treatment Outcome

Topiramate is effective as adjunctive treatment of partial-onset seizures in adults. The efficacy and safety of topiramate as adjunctive therapy for the treatment of primary generalized tonic-clonic (PGTC) seizures were investigated in a randomized, double-blind, placebo-controlled study.. Eighty patients, 3 to 59 years old, who experienced three or more PGTC seizures during an 8-week baseline phase were randomly assigned to treatment with either topiramate (n = 39) or placebo (n = 41). Topiramate was titrated to target doses of approximately 6 mg/kg/day over 8 weeks and maintained for another 12 weeks.. The median percentage reduction from baseline in PGTC seizure rate was 56.7% for topiramate patients and 9.0% for placebo patients (p = 0.019). The proportion of patients with 50% or higher reduction in PGTC seizure rate was 22/39 (56%) and 8/40 (20%) for the topiramate and placebo groups, respectively (p = 0.001). The median percentage reduction in the rate of all generalized seizures was 42.1% for topiramate patients and 0.9% for placebo patients (p = 0.003). The proportions of patients with 50% or higher reductions in generalized seizure rate were 18/39 (46%) and 7/41 (17%) for the topiramate and placebo groups, respectively (p = 0.003). The most common adverse events were somnolence, fatigue, weight loss, difficulty with memory, and nervousness. Treatment-limiting adverse events occurred in one patient in the topiramate group (anorexia and weight loss) and one in the placebo group (granulocytopenia and thrombocytopenia).. Topiramate is well-tolerated and effective for the adjunctive treatment of PGTC seizures.

Topics: Adolescent; Adult; Anticonvulsants; Child; Double-Blind Method; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Topiramate

Preliminary data concerning the effectiveness of topiramate (TPM) in the management of resistant primary generalized seizures were obtained from the open-label extension of a double-blind, placebo-controlled trial of TPM. The controlled trial enrolled patients experiencing three or more primary generalized tonic-clonic seizures (PGTCS) during an 8-week baseline period. Twelve of 13 patients who completed double-blind treatment elected to receive extended open therapy with TPM and were followed for periods ranging from 2 to 11 months. Of the 12 patients, 11 (92%) experienced a 50% or greater reduction in tonic-clonic seizures during their last 2 months of open-label TPM therapy compared to their pre-double-blind baseline period, and 7 (58%) were seizure-free during the open extension. Of five patients reporting absence seizures at baseline, four (80%) demonstrated a 50% or greater reduction in seizures. In seven of the 12 patients, a concomitant antiepileptic drug (AED) was discontinued or its dosage was reduced during open TPM treatment. The most common adverse events observed in the open study extension were weight reduction (five patients), weight increase (two patients), and drowsiness (two patients). The results of controlled trials are needed to determine the efficacy of TPM in primary generalized seizures. However, these preliminary findings are encouraging.

Topics: Adult; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Myoclonic; Epilepsy, Absence; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Middle Aged; Placebos; Topiramate; Treatment Outcome

Topics: Acetamides; Animals; Anticonvulsants; Benzazepines; Brain; Cardiovascular Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Electroshock; Epilepsy, Tonic-Clonic; Fructose; Ivabradine; Lacosamide; Lamotrigine; Male; Mice; Pregabalin; Topiramate; Triazines

Topics: Agenesis of Corpus Callosum; Anticonvulsants; Brain Neoplasms; Carbamazepine; Corpus Callosum; Epilepsy, Tonic-Clonic; Fructose; Humans; Lipoma; Magnetic Resonance Imaging; Male; Oxcarbazepine; Topiramate; Young Adult

We report a patient with a history of rare generalised tonic-clonic seizures and recurrent absence status who was diagnosed with a rare variant of idiopathic generalised epilepsy and absence status epilepsy. No other pathology was identified and MRI was normal. During a follow-up of 17 years, we recorded a single unilateral continuous, strictly subclinical, paroxysmal activity which lasted for at least several hours. No control was observed under treatment with phenobarbital, lamotrigine and topiramate. Absence status was aggravated with carbamazepine and generalised tonic-clonic seizures were not controlled with ethosuximide. Total seizure control was only possible with sodium valproate, which caused weight gain, and the patient has remained seizure-free for the past 10 years under 1,000 mg/d valproate and 200 mg/d topiramate. The recorded unilateral, long-lasting, subclinical spike-and-wave discharge is quite unusual for idiopathic generalised epilepsy and, in our opinion, occupies a transitional position between generalised and focal activity.

Topics: Adult; Anticonvulsants; Brain; Carbamazepine; Diagnosis, Differential; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Follow-Up Studies; Fructose; Humans; Lamotrigine; Phenobarbital; Secondary Prevention; Status Epilepticus; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Weight Gain

To study the impact of pregnancy on the serum concentration/dose ratio (C/D-ratio) of topiramate (TPM).. Twelve women with epilepsy using TPM during pregnancy, and 15 pregnancies were studied. The main target variable was the C/D-ratio at baseline and during pregnancy. Additional variables were changes in TPM dose, concomitant use of other antiepileptic drugs, seizure frequency, and pregnancy outcome. Clinical and pharmacological data were obtained from the women's medical records.. The average C/D-ratios in the second and third trimester were 30% (p = 0.002, n = 11) and 34% (p = 0.001, n = 8) lower than the baseline values, respectively. The interindividual variability was pronounced. Increased seizure frequency was common in pregnant women using TPM, but a correlation to the decline in TPM C/D-ratio could not be established from our data.. Dose-corrected serum concentrations of TPM appear to decline gradually throughout pregnancy. The underlying mechanisms are not known. Increased glomerular filtration may play a major role. During pregnancy, therapeutic drug monitoring of TPM may be useful.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Myoclonic; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Infant, Newborn; Metabolic Clearance Rate; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Topiramate; Treatment Outcome

The clinical manifestations of acute topiramate toxicity are described.. Seven cases of acute and acute-on-chronic topiramate toxicity observed in two clinical units of Polish Poison Control Centers in 2004-2005 were analyzed.. The patients were 4 women and 2 men aged between 16 and 38 (mean 21.0 +/- 8.4) years. The doses of topiramate ranged from 10.7 to 218 mg/kg. The most frequent symptom was somnolence (66.7%) and, vertigo, agitation, and mydriasis were less common (33.4%). One patient who was not previously treated with topiramate experienced three secondarily generalized tonic-clonic seizures. Metabolic acidosis, lasting for 3-7 days, was observed in four cases, and did not influence the outcome.. The clinical manifestations of acute poisonings with topiramate ranged from asymptomatic to severe, but no distant sequelae or fatalities were observed. The course of acute poisoning seems to be more severe in patients who were not previously treated with topiramate.

Topics: Acidosis; Adolescent; Adult; Anticonvulsants; Drug Overdose; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Poison Control Centers; Poland; Severity of Illness Index; Sleep Stages; Suicide, Attempted; Topiramate; Young Adult

Wicket spikes (WS) are a normal variant EEG pattern that sometimes can be mistaken for epileptiform activity. We present a patient with WS and idiopathic generalized epilepsy who had been wrongly diagnosed with focal epilepsy, which leads to the prescription of carbamazepine with severe aggravation of generalized tonic-clonic seizures. She was referred for presurgical assessment of refractory focal epilepsy but long-term video-EEG showed sharp theta waves over the temporal regions during awakening, with a typical aspect of WS during drowsiness, nREM sleep stages I-II, and rapid eye movements (REM) sleep. There were a few generalized spike-waves during sleep but interictal changes were increased in frequency at awakening with bursts of fast-generalized spike-waves. Carbamazepine was progressively withdrawn and the patient was progressively switched to zonisamide. The patient no longer complained of generalized tonic-clonic seizures. At one year follow-up, this patient receives zonisamide with valproate. She has remained seizure-free.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Clobazam; Clonazepam; Diagnostic Errors; Drug Therapy, Combination; Electroencephalography; Epilepsy, Temporal Lobe; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Isoxazoles; Middle Aged; Remission Induction; Sleep Stages; Temporal Lobe; Theta Rhythm; Topiramate; Valproic Acid; Zonisamide

The purpose of this study was to assess the effectiveness and tolerability of topiramate (TPM) as add-on therapy in children with Dravet syndrome and considered unsatisfactorily controlled using stiripentol. All the 36 patients having been treated with TPM in our centre in 2001 were retrospectively evaluated. Seventy percent of them still received stiripentol when TPM was introduced. The association of both drugs did not need any particular adaptation of dosages. The mean TPM follow-up was 13.3 months (4-25 months) and the mean optimal TPM dose was 3.2 mg/kg/d (0.6-9.2 mg/kg/d). Twenty eight children (78 %) showed more than 50 % reduction in the frequency of generalized tonic-clonic seizures and status epilepticus (SE), whereas 8 % had more than 50 % increase. Six patients (17 %) remained seizure-free for at least 4 months. The most frequently reported side-effects were gastrointestinal and behavioural disturbances. TPM had to be stopped in 17 % of patients, because of poor tolerability and/or lack of efficacy. Topiramate seems therefore to be helpful in Dravet syndrome, even in patients not satisfactorily controlled by stiripentol. Both drugs can be easily and safely associated.

Topics: Anticonvulsants; Dioxolanes; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Tonic-Clonic; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Retrospective Studies; Seizures, Febrile; Status Epilepticus; Topiramate; Treatment Outcome

Topics: Anticonvulsants; Carbamazepine; Child; Drug Therapy, Combination; Electroencephalography; Epilepsy; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Humans; Magnetic Resonance Imaging; Phenobarbital; Phenytoin; Topiramate; Valproic Acid

Profound language regression developed in three children with epilepsy 4 to 28 weeks after beginning topiramate (TPM). TPM was administered as an adjunctive antiepileptic drug at doses of 2.5 to 6.0 mg/kg/day. Language functions recovered while TPM was being reduced in dose or stopped.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy, Complex Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Language Disorders; Speech Disorders; Topiramate

The antiepileptic effects of topiramate (TPM) were assessed in two models of genetically determined generalized epilepsy. The model of nonconvulsive epilepsy used was a model of absence seizures, the GAERS (Genetic Absence Epilepsy Rat from Strasbourg); and the model of convulsive seizures was an audiogenic rat model, the Wistar Audiogenic Sensitive (AS) rat.. GAERS were equipped with four cortical electrodes over the frontoparietal cortex, and the duration of spike-and-wave discharges (SWDs) on the EEG was recorded for periods of 20 to 120 or 300 min. In Wistar AS, the occurrence of, latency to, and duration of one or two wild running episodes and tonic seizures were recorded.. In the 16 GAERS studied, TPM (10, 30, and 60 mg/kg) dose-dependently reduced the expression of SWD that almost totally disappeared at the two highest doses between 40 and 120 min. SWD duration returned to control levels by 180 and 280 min after the injection of 30 and 60 mg/kg TPM, respectively. In Wistar AS, 10 mg/kg TPM induced the occurrence of a second running episode not present in control rats, indicative of a decrease in sensitivity of the rats to the stimulus and increased by 330% the latency to the tonic seizure that still occurred in the eight rats studied. At 30 and 60 mg/kg, the latency to wild running increased by 140%; the second running episode was suppressed in six and seven rats, respectively, whereas the tonic seizure occurred only in one of the eight rats studied at these two doses.. These results support the broad spectrum of antiepileptic activity of TPM, confirming its efficacy in primary generalized seizures of both tonic-clonic and of the absence type.

Topics: Animals; Anticonvulsants; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Absence; Epilepsy, Generalized; Epilepsy, Reflex; Epilepsy, Tonic-Clonic; Evoked Potentials; Fructose; Rats; Rats, Wistar; Topiramate

In this study for the first time in alcohol withdrawal syndrome, the response to topiramate was assessed. 12 patients with median age of 49.5 years and median body weight of 76.3 kg were treated with topiramate twice daily for up 30 days, starting with a dose of 50 mg in the morning and 50 mg in the evening. The preliminary findings of this study suggest that topiramate is very effective against tonic-clonic seizures in alcohol withdrawal syndrome. No side effects were observed. Only two patients had loss of body weight (3-3.5 kg/4 weeks).

Topics: Alcohol Withdrawal Seizures; Anticonvulsants; Epilepsy, Tonic-Clonic; Fructose; Humans; Middle Aged; Pilot Projects; Topiramate

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Schizophrenia, Paranoid; Seizures; Topiramate; Treatment Outcome

To study the anticonvulsant action of topiramate (TPM) in developing rats.. Motor seizures were elicited by administering pentylenetetrazol (100 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 to 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-old rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated.. TPM did not influence minimal seizures (clonus of forelimb and head muscles with preserved righting ability). Generalized tonic-clonic seizures, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited generalized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80-mg/kg doses in the 7-day-old rat pups. The specific suppression of the tonic phase of generalized seizures was observed up to 12 hours in the 12-day-old rat pups. The same result was obtained over 6 hours after TPM administration in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group.. TPM exhibits stable anticonvulsant action against the tonic phase of generalized tonic-clonic seizures throughout development. In addition, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action.

Topics: Age Factors; Animals; Anticonvulsants; Behavior, Animal; Brain; Disease Models, Animal; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Injections, Intraperitoneal; Male; Motor Activity; Pentylenetetrazole; Rats; Rats, Wistar; Topiramate

The incidence of psychosis during clinical trials of topiramate was 0.8%, not significantly different from the rate for placebo or reported rates of psychosis in patients with refractory epilepsy. We observed psychotic symptoms in five patients soon after initiation of topiramate therapy. We performed a retrospective chart review of the first 80 patients who began on topiramate after approval for clinical use, between January and April 1997. Symptoms suggestive of psychosis, including hallucinations and delusions, were sought for analysis. Cognitive effects such as psychomotor slowing, confusion, and somnolence were not included. Five patients developed definite psychotic symptoms 2 to 46 days after beginning topiramate. Dosages at symptom onset were 50-400 mg/day. Symptoms included paranoid delusions in four patients and auditory hallucinations in three. Symptoms of psychosis and other psychiatric symptoms resolved quickly with discontinuation of topiramate in three patients, dose reduction from 300 to 200 mg/day in one and with inpatient treatment and neuroleptics in another. One patient had a history of auditory hallucinations, one of aggressive and suicidal thoughts, but three had no significant psychiatric history. Physicians should be aware of the possibility of psychotic symptoms, even in patients without a previous psychiatric history, when prescribing topiramate. Symptoms resolve quickly with discontinuation.

Topics: Adult; Anticonvulsants; Delusions; Dose-Response Relationship, Drug; Epilepsy, Complex Partial; Epilepsy, Post-Traumatic; Epilepsy, Tonic-Clonic; Female; Fructose; Hallucinations; Humans; Male; Middle Aged; Patient Care Team; Prognosis; Psychoses, Substance-Induced; Retrospective Studies; Topiramate

Topics: Anticonvulsants; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Fructose; Humans; Topiramate

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Fructose; Humans; Topiramate

The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Female; Fructose; Haloperidol; Male; Mice; Mice, Inbred DBA; Rats; Seizures; Topiramate