topiramate and Epilepsies--Partial

Epilepsy is one of the most common chronic neurological disorders, affecting more than 50 million people globally. In this review we summarised the evidence from randomised controlled trials of gabapentin used as monotherapy for the treatment of focal epilepsy, both newly diagnosed and drug-resistant, with or without secondary generalisation.. To assess the effects of gabapentin monotherapy for people with epileptic focal seizures with and without secondary generalisation.. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 24 February 2020) on 25 February 2020. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRA), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We also searched several Russian databases, reference lists of relevant studies, ongoing trials registers, conference proceedings, and we contacted trial authors.. We found five randomised controlled trials (3167 participants) comparing gabapentin to other antiepileptic drugs (AEDs) and differing doses of gabapentin as monotherapy for newly diagnosed focal epilepsy and drug- resistant focal epilepsy with or without secondary generalisation. Two review authors independently applied the inclusion criteria, assessed trial quality, risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence and present seven patient-important outcomes in the "Summary of findings" tables. The quality of evidence was very low to moderate due to poor reporting quality, poor trial design, and other risks of bias, such as selective presentation of findings and potential heavy industry input. Better quality research may change our certainty in the effect estimates. None of the included trials reported on the number of people with 50% or greater reduction in seizures and time to withdrawal (retention time) in an extractable way. Gabapentin-treated participants were more likely to withdraw from treatment for any cause (285/539) than those treated with lamotrigine, oxcarbazepine, or topiramate pooled together (695/1317) (RR 1.13, 95% CI 1.02 to 1.25; 3 studies, 1856 participants; moderate-certainty evidence), but not carbamazepine. Fewer people treated with gabapentin withdrew from treatment owing to adverse events (190/525) than those treated with carbamazepine, oxcarbazepine, or topiramate (479/1238), (RR 0.79, 95% CI 0.69 to 0.91; 1763 participants, 3 studies; moderate-certainty evidence), but not lamotrigine.. Gabapentin as monotherapy probably controlled seizures no better and no worse than comparator AEDs (lamotrigine, carbamazepine, oxcarbazepine, and topiramate). Compared to carbamazepine, gabapentin was probably better in retaining people in studies and preventing withdrawals due to adverse events. The most common side effects associated with gabapentin were ataxia (poor co-ordination and unsteady gait), dizziness, fatigue, and drowsiness.

Topics: Anticonvulsants; Carbamazepine; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Gabapentin; Humans; Lamotrigine; Oxcarbazepine; Seizures; Topiramate

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

Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).. We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016.. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events.. IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than both current first-line treatments carbamazepine and lamotrigine; lamotrigine performed better than all other treatments (aside from levetiracetam), and carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure types (moderate. Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.

Topics: Adult; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Network Meta-Analysis; Oxcarbazepine; Phenobarbital; Phenytoin; Piracetam; Remission Induction; Topiramate; Triazines; Valproic Acid; Zonisamide

In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel.

Topics: Adolescent; Adult; Aged; Aggression; Anticonvulsants; Child; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Hostility; Humans; Levetiracetam; Middle Aged; Nitriles; Piracetam; Pyridones; Topiramate; Treatment Outcome; Young Adult

Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).. We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016.. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events.. IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than current first-line treatment carbamazepine and other current first-line treatment lamotrigine performed better than all other treatments (aside from levetiracetam); carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure typ. Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.

Topics: Adult; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Network Meta-Analysis; Oxcarbazepine; Phenobarbital; Phenytoin; Piracetam; Remission Induction; Topiramate; 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

The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies and up to 30% from clinical series (not population-based) develop drug-resistant epilepsy, especially those with partial onset seizures. In this review we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add-on treatment for drug-resistant partial epilepsy. This is an updated version of the original Cochrane review published in Issue 3, 1999.. To evaluate the efficacy and safety of topiramate when used as an add-on treatment for people with drug-resistant partial epilepsy.. We searched the Cochrane Epilepsy Group Specialised Register (June 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 5); MEDLINE (1946 to 2013); SCOPUS (1823 to 2013); ClinicalTrials.gov and ICTRP. We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies.. Randomised, placebo-controlled or active drug controlled add-on trials of topiramate, recruiting people with drug-resistant partial epilepsy.. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (a) 50% or greater reduction in seizure frequency; (b) seizure freedom; (c) treatment withdrawal (any reason); (d) side effects. Primary analyses were intention-to-treat and summary risk ratios (RR) with 95% confidence intervals (95% CI) are presented. We evaluated dose response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall quality of evidence using the GRADE approach, which we presented in a 'Summary of findings' table.. Eleven trials were included, representing 1401 randomised participants. Baseline phases ranged from 4 to 12 weeks and double-blind phases from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency compared to placebo was 2.97 (95% CI 2.38 to 3.72). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 or 400 mg per day. The RR for seizure freedom (95% CI) compared to placebo was 3.41 (95% CI 1.37 to 8.51). The RR for treatment withdrawal compared to placebo was 2.44 (95% CI 1.64 to 3.62). The RRs for the following side effects indicate that they are significantly associated with topiramate: ataxia 2.29 (99% CI 1.10 to 4.77); concentration difficulties 7.81 (2.08 to 29.29); dizziness 1.54 (99% CI 1.07 to 2.22); fatigue 2.19 (99% CI 1.42 to 3.40); paraesthesia 3.91 (1.51 to 10.12); somnolence 2.29 (99% CI 1.49 to 3.51); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38) and weight loss 3.47 (1.55 to 7.79). Evidence of publication bias was found (P-value from the Egger test was P=0.003). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate quality due to the evidence of publication bias.. Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy in that it is three times more effective compared to a placebo in reducing seizures. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of topiramate. In the short term topiramate as an add-on has been shown to be associated with several adverse events. The results of this review cannot be extrapolated to monotherapy or treatment of other epilepsy types and future research should consider examining the effect of dose.

Topics: Anticonvulsants; Drug Resistance; Epilepsies, Partial; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate; Treatment Failure

Secondary generalized tonic-clonic seizures (SGTCS) are among the most severe forms of seizures, and the main risk factor for sudden unexpected death in epilepsy (SUDEP). Whether some antiepileptic drugs (AEDs) might be more efficacious than others on SGTCS in patients with drug-resistant focal epilepsy thus represents an important clinical issue for which no data are currently available.. We performed a meta-analysis of randomized controlled trials of adjunctive AED in which information on efficacy outcomes (i.e., responder rate and/or frequency per 28 days relative to baseline) were available both for all seizure types and for SGTCS. The primary analysis evaluated the efficacy of AEDs on all types of seizure and on SGTCS by comparing the responder rates for AED and for placebo.. Responder rate was available both for all seizure types and for SGTCS in 13 of the 72 eligible trials, evaluating 7 AEDs. Only three AEDs--lacosamide, perampanel and topiramate--showed greater efficacy than placebo. However, confidence intervals of relative risks overlapped for all AEDs but pregabalin, which demonstrated significantly lower efficacy than lacosamide, perampanel, and topiramate. Moreover, there was a nonsignificant trend toward a lower relative risk of responder rate for SGTCS than for all seizure types, which appeared related to a greater response to placebo for this outcome.. Indirect comparison of AEDs using randomized placebo-controlled add-on trials does not support robust differences between AEDs to prevent SGTCS. Alternative designs for evaluation of therapeutic interventions in patients at risk for SGTCS-related complications are required.

Topics: Acetamides; Anticonvulsants; Chronic Disease; Death, Sudden; Early Medical Intervention; Epilepsies, Partial; Fructose; Humans; Lacosamide; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Seizures; Topiramate; Treatment Outcome

Epilepsy is a common neurological condition, affecting almost 0.5 to 1% of the population. Nearly 30% of people with epilepsy are resistant to currently available drugs. Tiagabine is one of the newer antiepileptic drugs and its effects as an adjunct (add-on) to standard drugs are assessed in this review.. To evaluate the effects of add-on treatment with tiagabine upon seizures, adverse effects, cognition and quality of life for people with drug-resistant localisation related seizures.. This is an updated version of the original Cochrane review published in issue 10, 2010. We searched the Cochrane Epilepsy Group's Specialised Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 4, 2011 of The Cochrane Library), and MEDLINE (1948 to November 2011). No language restrictions were imposed. We also contacted the manufacturers of tiagabine and experts in the field to seek any ongoing or unpublished studies.. Randomised placebo controlled add-on trials of people of any age with localisation related seizures, in which an adequate method of concealment of randomisation was used were included. The studies could be double, single or unblinded and be of parallel or crossover design. They had to have a minimum treatment period of eight weeks. Trials using an active drug control group were also included.. Two review authors independently selected trials for inclusion and extracted data. Any disagreements were resolved by discussion. Outcomes investigated included 50% or greater reduction in seizure frequency; treatment withdrawal; adverse effects; effects on cognition and quality of life. The primary analyses were by intention-to-treat. Worst case and best case analyses were also calculated for seizure outcomes. Dose response was evaluated in regression models.. Four parallel group and two crossover group trials were included. The overall relative risk (RR) with 95% confidence intervals (CIs) for a 50% or greater reduction in seizure frequency (tiagabine versus placebo) was 3.16 (95% CI 1.97 to 5.07). Due to differences in response rates among trials, regression models were unable to provide reliable estimates of responses to individual doses. The RR for treatment withdrawal was 1.81 (95% CI 1.25 to 2.62). The 99% CIs for the following adverse effects: dizziness; fatigue; nervousness and tremor did not include unity, indicating that they are significantly associated with tiagabine. For cognitive and quality of life outcomes the limited data available suggested that there were no significant effects on cognition and mood and adjustment.. Tiagabine reduces seizure frequency but is associated with some adverse effects when used as an add-on for people with drug-resistant localisation-related seizures.

Topics: Anticonvulsants; Cognition; Drug Resistance; Epilepsies, Partial; Fructose; Humans; Nipecotic Acids; Quality of Life; Randomized Controlled Trials as Topic; Tiagabine; Topiramate

Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in partial refractory epilepsy.. Systematic review of randomized trials (RCTs) comparing a new AED (add-on treatment) with placebo or another AED.. responder (≥50% seizure reduction) and withdrawal (tolerability) rates. Pooled estimates of odds ratios (ORs) and number needed treat/harm (NNT/NNH) taking into account baseline risk were derived by random-effects meta-analysis. Adjusted frequentist indirect comparisons between AEDs were estimated.. Sixty-two placebo-controlled (12,902 patients) and eight head-to-head RCTs (1,370 patients) were included. Pooled ORs for responder and withdrawal rates (vs. placebo) were 3.00 [95% confidence interval (CI) 2.63-3.41] and 1.48 (1.30-1.68), respectively. Indirect comparisons of responder rate based on relative measurements of treatment effect (ORs) favored topiramate (1.52; 1.06-2.20) in comparison to all other AEDs, whereas gabapentin (0.67; 0.46-0.97) and lacosamide (0.66; 0.48-0.92) were less efficacious, without significant heterogeneity. When analyses were based on absolute estimates (NNTs), topiramate and levetiracetam were more efficacious, whereas gabapentin and tiagabine were less efficacious. Withdrawal rate was higher with oxcarbazepine (OR 1.60; 1.12-2.29) and topiramate (OR 1.68; 1.07-2.63), and lower with gabapentin (OR 0.65; 0.42-1.00) and levetiracetam (OR 0.62; 0.43-0.89).. The differences found are of relatively small magnitude to allow a definitive conclusion about which new AED(s) has superior effectiveness. This uncertainty probably reflects the limitations of conclusions based on indirect evidence. The process of pharmacologic clinical decision making in partial refractory epilepsy probably depends more on other aspects, such as individual patient characteristics and pharmacoeconomics, than on available controlled randomized evidence.

Topics: Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Nipecotic Acids; Piracetam; Randomized Controlled Trials as Topic; Tiagabine; Topiramate; Treatment Outcome

The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies and up to 30% from clinical series (not population-based) develop drug-resistant epilepsy, especially those with partial onset seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug-resistant partial epilepsy.. To evaluate the efficacy and safety of topiramate when used as an add-on treatment for drug-resistant partial epilepsy.. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2007); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007). No language restrictions were imposed. We also contacted the manufacturers of topiramate and researchers in the field to see any ongoing or published studies.. Randomized placebo controlled add-on trials of topiramate recruiting people with drug-resistant partial epilepsy.. Two review authors independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary relative risks (RR) with 95% confidence intervals (95% CI) are presented. Dose response was evaluated in regression models.. Ten trials were included representing 1312 randomized participants. Baseline phases ranged from 4-12 weeks and double-blind phases from 11-19 weeks. The RR for a 50% or greater reduction in seizure frequency compared to placebo was 2.85 (95% CI 2.27 to 3.59). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 or 400 mg per day. The RR for treatment withdrawal compared to placebo was 2.26 (95% CI 1.55 to 3.31). The RR for the following side effects indicate that they are significantly associated with topiramate: ataxia 1.95 (99% CI 1.04 to 3.65); dizziness 1.55 (99% CI 1.08 to 2.22); fatigue 2.19 (99% CI 1.43 to 3.35); nausea 2.35 (99% CI 1.28 to 4.29); somnolence 2.18 (99% CI 1.47 to 3.21) and 'thinking abnormally' 5.77 (99% CI 2.50 to 13.35).. Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long-term efficacy of topiramate. Results cannot be extrapolated to monotherapy or treating other epilepsy types.

Topics: Anticonvulsants; Drug Resistance; Epilepsies, Partial; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate; Treatment Failure

Topics: Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Dioxolanes; Epilepsies, Partial; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Oxcarbazepine; Piracetam; Pregabalin; Topiramate; Triazines; Vigabatrin; Zonisamide

Special issues are related to AED testing in several populations. Pharmacokinetics, pharmacodynamics and underlying neurochemistry and developing systems require specific testing in appropriate infants with refractory seizures. EEG monitoring is an essential part of seizure definition and recognition, making it a necesssity along with clinical semiology to define the seizure types and changes in seizure frequency. (1) Neonates: A trial design for neonatal seizures should be similar to those used for the treatment of status epilepticus. Proposed study end points should be seizure cessation for some period of time, or time to next seizure. The use of placebo is questionable. (2) Partial seizures occurring in young infants: A trial designed for topirimate included a placebo controlled, double blind study with fixed dose trials exploring the range of tolerated doses. Forty-eight hour video EEGs were used for quantification of seizures. (3) Uncommon forms of encephalopathic epilepsy: a proposed design includes randomization to sequential monotherapy with prescribed titration/dose defined by seizure control or tolerance. Outcome variables include seizure reduction, tolerability, and time continued on AED.

Topics: Anticonvulsants; Clinical Trials as Topic; Electroencephalography; Epilepsies, Partial; Epilepsy; Fructose; Humans; Infant; Infant, Newborn; Topiramate; Video Recording

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.. A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003.. Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking.. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Topics: Acetates; Adolescent; Adult; Age Factors; Amines; Antipsychotic Agents; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Approval; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; United States; United States Food and Drug Administration; Zonisamide

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies.. A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003.. All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome.. The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Topics: Acetates; Adolescent; Adult; Age Factors; Amines; Anticonvulsants; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Approval; Epilepsies, Partial; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Practice Patterns, Physicians'; Tiagabine; Topiramate; Triazines; United States; United States Food and Drug Administration; Zonisamide

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies.. A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003.. All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome.. The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Topics: Acetates; Adult; Amines; Anticonvulsants; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Resistance; Epilepsies, Partial; Epilepsy, Generalized; Evidence-Based Medicine; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 30 per cent develop drug-resistant epilepsy, especially those with partial onset seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug resistant partial epilepsy.. To evaluate the effects of topiramate when used as an add-on treatment for drug-resistant partial epilepsy.. We searched the Cochrane Epilepsy Group's specialized register (28 March 2002); the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2002). In addition, we contacted Johnson and Johnson (makers of topiramate) and experts in the field to seek any ongoing or unpublished studies.. Randomized placebo controlled add-on trials of topiramate recruiting people with drug-resistant partial epilepsy.. Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50 per cent or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary relative risks (RR) with 95% confidence intervals (95% CI) are presented. Dose response was evaluated in regression models.. Nine trials were included representing 1049 randomized participants. The RR for a 50 per cent or greater reduction in seizure frequency compared to placebo was 3.32(95% CI 2.52 to 4.39). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 mg per day. The RR for treatment withdrawal compared to placebo was 2.06(95% CI 1.38 to 3.08). The RR for the following side effects indicate that they are significantly associated with topiramate: 1.95(99% CI 1.04 to 3.65), dizziness 1.55(99% CI 1.07 to 2.24); fatigue 2.21(99% CI 1.42 to 3.45); nausea 2.75(99% CI 1.36 to 5.57); somnolence 2.26(99% CI 1.48 to 3.46) and 'thinking abnormally' 5.54(99% CI 2.34 to 13.12).. Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of topiramate. Results cannot be extrapolated to monotherapy or treating other epilepsy types.

Topics: Anticonvulsants; Drug Resistance; Epilepsies, Partial; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate; Treatment Failure

Idiopathic epilepsies comprise a wide variety of partial and generalized syndromes that have in common a known or presumed genetic etiology and the lack of overt abnormalities other than the epilepsy itself. Most of these epilepsies have a benign natural history and/or show a favorable response to antiepileptic drug (AED) therapy, but pharmacoresistance does occur in some patients. In general, therapeutic algorithms in idiopathic partial epilepsies (IPEs) are similar to those used for symptomatic partial epilepsies, but aggressive pharmacologic therapy is rarely indicated in these patients. In self-limited conditions such as benign epilepsy of childhood with centrotemporal spikes or some forms of benign epilepsy with occipital paroxysms, AED treatment may not even be indicated unless seizures interfere significantly with quality of life. Valproate (VPA) is usually regarded as the drug of choice in idiopathic generalized epilepsies (IGEs). Most patients become rapidly seizure free, and poor compliance or prescription of an inappropriate AED because of misdiagnosis are the most common causes of treatment failure in IGEs. In those patients who did not respond well to VPA (or in whom VPA is considered contraindicated), the choice of alternative AEDs is guided by syndromic diagnosis and associated possible coexistence of multiple seizure types. Lamotrigine is establishing itself as a useful agent for many refractory IGEs, and might be considered for first-line use in selected patients. Topiramate (TPM) is another promising new agent in the management of refractory tonic-clonic seizures of nonfocal onset, but its potential efficacy against other primarily generalized seizure types has not been clearly established. Some of the older drugs, particularly ethosuximide (ESM), barbiturates, and benzodiazepines (BZDs), still have an important role in the management of refractory IGEs, especially in combination with VPA. Because carbamazepine (CBZ), phenytoin (PHT), tiagabine (TGB), vigabatrin (VGB), and gabapentin (GBP) may precipitate or aggravate absence and/or myoclonic jerks, their role in IGE syndromes associated with multiple seizure types is limited mostly to adjunctive use in patients unresponsive to first-line therapy.

Topics: Adolescent; Anticonvulsants; Child; Clinical Protocols; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fructose; Humans; Lamotrigine; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Six double-blind, placebo-controlled trials were conducted with topiramate (TPM) initiated as adjunctive therapy in adults with treatment-resistant partial-onset seizures with or without secondary generalization.. Because protocols and study populations were similar, data from the studies were pooled and analyzed for 527 patients treated with TPM and 216 treated with placebo.. Seizures were reduced > or =50% in 43% of TPM-treated patients and in 12% of placebo-treated patients (p < 0.001); 5% of TPM-treated patients, but no placebo-treated patients, were seizure free during 11-19 weeks of double-blind treatment (p < 0.001). The therapeutic effect was consistent regardless of seizure type, age, gender, baseline seizure rate, or concomitant antiepileptic drug (AED). With 100 mg/day TPM as a starting dosage and weekly dosage increments of 100-200 mg/day added to maximally tolerated dosages of AEDs, the most common treatment-emergent adverse events (TEAEs) were dizziness, somnolence, fatigue, psychomotor slowing, nervousness, paresthesia, ataxia, memory difficulty and speech problems. These central nervous system effects were generally mild to moderate in severity, usually occurred early in treatment, often during titration, and resolved with continued treatment. Other notable TEAEs were weight loss and, in a small percentage of patients, renal calculi.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Humans; Middle Aged; Placebos; Randomized Controlled Trials as Topic; Topiramate

The majority of epileptic patients have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug-resistant partial epilepsy.. To evaluate the efficacy and tolerability of topiramate when used as an add-on treatment in patients with drug resistant partial epilepsy.. (a) The Cochrane Library (1999 Issue 1); (b) The controlled trial register of the Cochrane Epilepsy Group; (c) Johnson and Johnson, makers of topiramate; (d) Experts in the field.. Randomized placebo controlled add-on trials of topiramate in patients with drug resistant epilepsy.. Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Summary odds ratios (OR) were estimated for each outcome. Dose response was evaluated in regression models.. Six trials were included representing 743 randomized patients.. Overall OR (95% CIs) for 50% or greater reduction in seizure frequency compared to placebo 4.06 (2.86-5.78). Dose regression analysis shows increasing efficacy with increasing dose, but found no advantage for doses over 400 mg per day. Global effectiveness: treatment withdrawal OR (95% CIs) compared to placebo 2.57 (1.65-4.00). Side effects: OR (99% CIs)compared to placebo, dizziness 1.99 (1.20-3.29); fatigue 2.52 (1. 47-4.32); nausea 2.84 (1.36-5.93); somnolence 2.89 (1.72-4.85) and 'thinking abnormally' 3.71 (2.02-6.80) were significantly associated with topiramate.. Topiramate has efficacy as an add-on treatment in patients with drug resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of topiramate. Results cannot be extrapolated to monotherapy or patients with other epilepsy types.

Topics: Anticonvulsants; Epilepsies, Partial; Fructose; Humans; Topiramate; Treatment Failure

Topiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. Since topiramate hardly affects the threshold of the seizure, topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (gamma-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.

Topics: Animals; Anticonvulsants; Chlorine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epilepsies, Partial; Fructose; gamma-Aminobutyric Acid; Humans; Receptors, AMPA; Sodium Channel Blockers; Topiramate

Topiramate (Topamax) has been registered since July 1998 and has market authorization for the Federal Republic of Germany as an additive drug for the treatment of patients (age 12 or older) suffering from intractable partial and secondarily generalized seizures. The anticonvulsant effect of topiramate is based on three mechanisms: (a) modulating the blocking of the Na channels activated by voltage, depending on status, (b) potentiation of GABAA-mediated inhibiting neurotransmission, and (c) inhibition of excitatory neurotransmission by blocking APMA glutamate receptors. Topiramate exhibits a substantial anticonvulsive effect on partial seizures both with and without secondary generalization. The median reduction in seizure frequency using topiramate as adjunct therapy was 44%. In 44% of patients, seizure frequency was reduced by more than 50%, and seizure reduction was more than 75% in nearly half of these (i.e., in 21% of all patients), while 5% of patients remained completely free of seizures. Adverse events most often caused central nervous disturbances. Weight loss, the development of renal calculi, and impairment of cognitive functions may occur. It is recommended to start therapy with topiramate at a daily dosage of 25 mg, increasing by 25 mg every week up to 200-400 mg/day but not exceeding 1000 mg/day.

Topics: Anticonvulsants; Controlled Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Europe; Fructose; Humans; Topiramate; United States

Since 1993, several new antiepileptic drugs (AEDs) have been introduced for management of partial seizures. Like the established AEDs, the new drugs are believed to exert their anticonvulsant action through enhancement of inhibitory-mediated neurotransmission, or reduction of excitatory-mediated neurotransmission, or by a combination of both. Among the new drugs, vigabatrin (VGB) and tiagabine (TGB) are unique in that they were derived from mechanistic-based drug discovery programs designed to identify effective AEDs that inhibit the metabolism and reuptake of the inhibitory neurotransmitter GABA, respectively. For many of the newer AEDs, several molecular mechanisms of action have been identified. For example, felbamate (FBM), lamotrigine (LTG), zonisamide (ZNS), topiramate (TPM), oxcarbazepine (OCBZ), and possibly gabapentin (GBP) share a similar mechanism with that defined for phenytoin (PHT) and carbamazepine (CBZ), i.e., a voltage- and use-dependent block of voltage-sensitive sodium (Na+) channels. In addition to their effects on Na+ currents, TPM, ZNS, and FBM also appear to act as allosteric modulators of the GABA(A) receptor, whereas GBP appears to increase brain GABA levels. GBP, ZNS, FBM, LTG, and OCBZ attenuate voltage-sensitive calcium (Ca2+) channels, albeit through different mechanisms and with different classes of Ca2+ channels. FBM and TPM differ from both the established and newer AEDs in their ability to modulate NMDA- and AMPA/kainate-mediated excitatory neurotransmission, respectively. The multiple mechanisms of action associated with FBM, TPM, ZNS, GBP, and perhaps LTG, and the unique modulation of GABA levels by VGB and TGB, are likely to account for the anticonvulsant efficacy of these newer AEDs in patients with epilepsy. For each of the new drugs, their proposed mechanisms of action are discussed in relationship to their preclinical and clinical anticonvulsant profiles.

Topics: Animals; Anticonvulsants; Carbamazepine; Disease Models, Animal; Epilepsies, Partial; Felbamate; Fructose; Humans; Isoxazoles; Lamotrigine; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Propylene Glycols; Receptors, GABA; Sodium Channels; Synaptic Transmission; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

Evidence based health care uses systematic literature reviews with statistical strategies like meta-analysis to aid decision-making. This information can help clinicians by organizing data and providing up-to-date quantitative summaries of efficacy and adverse effects of treatments. Limitations of meta-analysis include problems inherent in combining data from trials of somewhat different design, choice of appropriate dosages, and summarizing complex questions as a single odds ratios. I summarize the results of a meta-analysis of the following antiepileptic treatments for partial seizures in adults: gabapentin, lamotrigine, topiramate, tiagabine, valproate and the vagal nerve stimulator. Each treatment was significantly more efficacious than placebo, and there were nonsignificant trends toward differences among the treatments in efficacy and tolerability. Quantitative analysis of adverse effects is presented. Absent the availability of a comprehensive randomized controlled trial for comparison, a rigorously conducted meta-analysis provides some useful information.

Topics: Acetates; Adult; Amines; Anticonvulsants; Confidence Intervals; Cyclohexanecarboxylic Acids; Drug Administration Schedule; Electric Stimulation Therapy; Epilepsies, Partial; Evidence-Based Medicine; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Nipecotic Acids; Odds Ratio; Randomized Controlled Trials as Topic; Tiagabine; Topiramate; Triazines; Vagus Nerve

Six studies are cited to demonstrate that topiramate is effective as adjunctive therapy for refractory partial-onset seizures in adults. Subsequent studies indicate that topiramate is also effective as monotherapy in adults and as adjunctive therapy for partial-onset seizures in children, tonic-clonic seizures of nonfocal origin in children and adults, and drop attacks in Lennox-Gastaut syndrome. Adverse effects for adults and children included dizziness, fatigue, ataxia, confusion, somnolence, nephrolithiasis, paresthesia, and weight loss. More adverse effects were observed at higher doses. Topiramate exhibits rapid absorption, long duration of action, and minimal interaction with other antiepileptic drugs.

Topics: Adult; Anticonvulsants; Ataxia; Child; Clinical Trials as Topic; Dizziness; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Fatigue; Fructose; Humans; Topiramate; Treatment Outcome

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage of topiramate are reviewed. Topiramate is indicated for use in the adjunctive treatment of adult partial-onset epilepsy. A sulfamate-substituted monosaccharide, it is structurally distinct from other antiepileptic agents. Topiramate acts by blocking the spread of seizures. Oral topiramate has high bioavailability and low protein binding, and as monotherapy its half-life permits once- or twice-daily administration. The drug is excreted largely unchanged in the urine. Clinical trials have shown that topiramate is effective as adjunctive therapy in treating adult partial-onset epilepsy with or without secondarily generalized seizures. In adults with refractory partial epilepsy, topiramate has shown efficacy when carbamazepine or phenytoin has failed. Topiramate may also be effective against partial-onset epilepsy and Lennox-Gastaut syndrome in children, but more pediatric studies are needed. CNS adverse effects are the most common; weight loss and nephrolithiasis have also been reported. The drug does not appear to interact significantly with other antiepileptic agents, but enzyme inducers like phenytoin and carbamazepine can decrease serum topiramate levels by 50%. The initial dosage is 50 mg nightly for seven nights, followed by an increase weekly to 400 mg/day in two divided doses. Topiramate is more costly than other anticonvulsants; however, drug therapy accounts for less than 10% of the total direct cost of epilepsy treatment. Topiramate offers an effective, well-tolerated option in patients with adult partial-onset seizures.

Topics: Anticonvulsants; Epilepsies, Partial; Fructose; Humans; Topiramate

In controlled clinical trials, topiramate (Topamax) has demonstrated efficacy in refractory patients with complex partial seizures and secondarily generalized tonic-clonic seizures. Approximately 45 percent of 534 patients had a > or = 50 percent reduction in seizure frequency. Limited open label trials have shown that topiramate has broad spectrum activity and may be effective in patients with primary generalized epilepsies. The efficacy of topiramate compares very favourably with the efficacy of other new antiepileptic drugs recently introduced.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Generalized; Fructose; Humans; Topiramate

Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Drug Interactions; Epilepsies, Partial; Epilepsy; Felbamate; Fructose; gamma-Aminobutyric Acid; Humans; Lamotrigine; Nipecotic Acids; Phenylcarbamates; Propylene Glycols; Teratogens; Tiagabine; Topiramate; Triazines; Vigabatrin

A pooled analysis of data from five similarly designed double-blind, placebo-controlled trials of topiramate (TPM) as add-on therapy in patients with partial epilepsy was performed. The pooled analysis allowed evaluation of efficacy end points and response to treatment for a number of study subgroups not statistically evaluable in the individual study analyses due to limited sample sizes. The five trials included 534 patients, 360 who received TPM at target dosages of 200-1,000 mg daily and 174 who received placebo. In the intent-to-treat pooled analysis, TPM was significantly (p < or = 0.01) superior to placebo in reducing total seizures by > or = 75% or by 100%. When seizure types were evaluated independently, TPM significantly (p < or = 0.001) reduced the frequency of simple partial, complex partial, and secondarily generalized seizures. TPM was significantly (p < 0.001) better than placebo regardless of gender, patient age, baseline seizure rate, and concomitant AEDs. The efficacy of TPM in partial epilepsy is consistent across efficacy end points and across strata defined by study population characteristics.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Multicenter Studies as Topic; Placebos; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

Because initial studies of new antiepileptic drugs (AEDs) are add-on trials in refractory patient populations, their effectiveness as monotherapy is usually not apparent until relatively later in their development programs. The novel AED topiramate (TPM) has been found efficacious as adjunctive therapy in controlled, randomized trials in adults with partial onset seizures. We report a retrospective analysis of TPM as AED monotherapy in 214 patients from five centers who received TPM in investigational trials. Of this total, 136 (64%) were still receiving TPM at the time of the analysis, with a mean treatment duration of 2.5 years. One-third of the patients have been successfully converted to TPM monotherapy, and 62% of those converted have been seizure-free for at least 3 months. The results of this analysis suggest that TPM may prove to be a valuable new AED for both monotherapy and add-on therapy in partial onset epilepsy.

Topics: Adult; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Drugs, Investigational; Epilepsies, Partial; Follow-Up Studies; Fructose; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Topiramate; Treatment Outcome

To review proposed mechanisms of action, clinical pharmacology, efficacy, safety, and tolerability of the antiepileptic drug (AED) topiramate.. All available data from the clinical development program--published and unpublished data (provided by investigators or the RW Johnson Pharmaceutical Research Institute)--were analyzed, with emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term efficacy and tolerability.. Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or without secondary generalization. In the refractory adult patient population enrolled in controlled clinical trials, seizures were reduced by 50% or more in 27-47% of patients compared with 0-18% in placebo-treated patients and by 75% or more in 9-36% of the patients compared with 0-9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Adverse effects include somnolence, fatigue, psychomotor slowing, and concentration problems. The currently recommended dosing is lower and titration slower than schedules used in the clinical trials; this may improve the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in some patients. Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used with enzyme-inducing AEDs. Open-label data and a single double-blind trial suggest that topiramate monotherapy may be effective. Open-label data also indicate that topiramate may be effective in generalized seizures of nonfocal origin, including those associated with Lennox-Gastaut syndrome.. The robust clinical effects of topiramate expand the therapeutic options for patients with epilepsy. Controlled clinical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to directly compare efficacy and tolerability with other new and standard AEDs.

Topics: Adult; Aged; Anticonvulsants; Child; Drug Interactions; Drug Monitoring; Epilepsies, Partial; Epilepsy, Generalized; Fructose; Humans; Male; Topiramate

To date, 1,809 individuals have been exposed to topiramate (TPM), primarily adults with partial-onset seizures. Of this total, 665 patients have been treated for more than 1 year, 177 for more than 3 years, and 67 for more than 5 years. The profile of treatment-emergent adverse reactions (TEAEs) observed with TPM at various dosages is based primarily on data from five double-blind, placebo-controlled trials in which 360 patients received TPM at target doses of 200-1,000 mg/day. Long-term safety is assessed on the basis of 1,001 patients treated with TPM in controlled and open trials for up to 5.3 years. Most of the commonly reported TEAEs were related to the central nervous system and were observed with greater frequency at dosages above the 200-600-mg/day range found to be optimal in dose ranging trials. Nephrolithiasis not requiring surgery was seen in 1.5% of patients, and mild, dose-related weight loss was associated with TPM therapy. No clinically significant treatment-related abnormalities were observed in clinical laboratory parameters or in neurologic, electrocardiographic, ophthalmologic, or audiologic tests.

Topics: Adult; Anticonvulsants; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Fructose; Humans; Incidence; Kidney Calculi; Male; Middle Aged; Multicenter Studies as Topic; Topiramate; Treatment Outcome; Weight Loss

A number of new antiepileptic drugs (AEDs), including topiramate (TPM), felbamate (FBM), and gabapentin (GBP), are approved or believed to be close to approval for marketing in the United States. Key efficacy findings for these AEDs in refractory partial epilepsy were reviewed. Large and significant drug-placebo differences were observed with TPM in two large dose-finding trials conducted in the United States. The minimal effective dose of TPM in the population studied was determined to be approximately 200 mg/day, and doses above 600 mg/day produced good efficacy but little incremental benefit versus the lower dosages for the overall study population. FBM is active in partial epilepsy, although seizure reduction is less marked and drug interactions complicate the findings. GBP is also active in this population, but only the 1,800 mg/day dosage was significantly better than placebo with respect to percent responders. It may be useful to explore higher dosage ranges for both FBM and GBP if they can be well tolerated.

Topics: Acetates; Adolescent; Adult; Aged; Amines; Anticonvulsants; Controlled Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Administration Schedule; Epilepsies, Partial; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Middle Aged; Phenylcarbamates; Placebos; Propylene Glycols; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; United States

Results of double-blind, placebo-controlled, add-on trials of topiramate (TPM), lamotrigine (LTG), and vigabatrin (VGB) in refractory partial epilepsy were reviewed. In three European multicenter studies of TPM, the clinical efficacy of 400-, 600-, and 800-mg/day target dosages was demonstrated. In a similarly designed United States trial, LTG was significantly superior to placebo at a 500-mg/day dosage but not at a 300-mg/day dosage. A meta-analysis of a number of smaller trials of VGB suggests that a > or = 50% reduction in seizures is observed in approximately 45% of patients with refractory partial epilepsy. All of these newer antiepileptic drugs have shown efficacy in well-controlled trials and should contribute significantly to our ability to manage partial epilepsy.

Topics: Anticonvulsants; Controlled Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Multicenter Studies as Topic; Placebos; Topiramate; Treatment Outcome; Triazines; Vigabatrin

Topiramate (Topamax-Janssen-Cilag Ltd) is a new drug for the treatment of adults with epilepsy. It is licensed for adjunctive treatment of partial seizures, with or without secondary generalisation, poorly controlled by conventional first-line regimens. Topiramate is the third add-on treatment for epilepsy to be marketed in the last 4 years. Does it have a specific place in the treatment of epilepsy?

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate

The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea.. In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes.. Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM.. In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures.

Topics: Adult; Anticonvulsants; Dizziness; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Headache; Humans; Levetiracetam; Male; Middle Aged; Republic of Korea; Seizures; Sleepiness; Topiramate

Assess cognitive effects of adjunctive perampanel in adolescents.. In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1-3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8-12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT).. One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, -0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (-6.9 vs. -2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. -1.2; p = 0.012), and worsening in Continuity of Attention (-3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%).. Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain.

Topics: Acetamides; Adolescent; Anticonvulsants; Attention; Carbamazepine; Child; Cognition; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Lacosamide; Lamotrigine; Levetiracetam; Male; Memory, Short-Term; Neuropsychological Tests; Nitriles; Oxcarbazepine; Piracetam; Pyridones; Topiramate; Treatment Outcome; Triazines; Valproic Acid

The aim of this study was to evaluate long-term safety, efficacy, and quality of life (QOL) of ≤400-mg/day USL255, Qudexy® XR (topiramate) extended-release capsules, as adjunctive therapy for partial-onset seizures (POS) in adults.. Patients who completed the 11-week double-blind treatment phase of the phase 3 PREVAIL study were eligible to enroll in this 1-year open-label extension (OLE) study (PREVAIL OLE). The primary objective was to evaluate the safety and tolerability of USL255 (including treatment-emergent adverse events [TEAEs]). The secondary objective was to assess seizure frequency in patients (e.g., median percent reduction from baseline in weekly POS frequency, responder rate [proportion of patients with ≥25%, ≥50%, ≥75%, or 100% reduction from baseline in POS frequency], and seizure-free intervals [proportion of patients who were seizure-free for 4, 12, 24, 36, or 48weeks]). Exploratory clinical-status endpoints included the Global Impression of Change (CGI-C) and Quality of Life in Epilepsy-Problems (QOLIE-31-P) questionnaires. Post hoc analyses evaluated neurocognitive TEAE incidences during the first 11 and entire 55weeks of treatment and efficacy by patient age and drug-resistant status.. Of the 217 patients who completed PREVAIL (USL255, n=103; placebo, n=114), 210 (97%) enrolled in PREVAIL OLE and were included in the ITT population. Across the entire 55-week treatment period, USL255 was generally safe and well tolerated, with low individual neurocognitive TEAE incidences. Seizure reduction was sustained across the year-long study and observed in patient subgroups, including those with highly drug-resistant seizures and those ≥50years of age. Improvements in CGI-C and QOLIE-31-P were also observed.. The results of PREVAIL OLE are consistent with those from PREVAIL and demonstrate that adjunctive treatment with up to 400mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.

Topics: Adult; Aging; Anticonvulsants; Cognition Disorders; Delayed-Action Preparations; Double-Blind Method; Drug Resistant Epilepsy; Epilepsies, Partial; Female; Fructose; Humans; Male; Quality of Life; Seizures; Surveys and Questionnaires; Topiramate; Treatment Outcome

To evaluate the efficacy and safety of USL255, Qudexy(™) XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs.. In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥ 50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated.. Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life.. The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Topiramate; Treatment Outcome; Young Adult

Results from a previously conducted global phase III study (PREVAIL; NCT01142193) demonstrate the safety and efficacy of once-daily USL255, Qudexy™ XR (topiramate) extended-release capsules, as adjunctive treatment of drug-resistant partial-onset seizures (POSs). In this study, we report a post hoc analysis of PREVAIL data according to patient level of treatment resistance (based upon the number of concomitant antiepileptic drugs [AEDs] and lifetime AEDs) at baseline, with patients defined as either having "highly" drug-resistant seizures (≥ 2 concurrent AEDs and ≥ 4 lifetime AEDs) or having "less" drug-resistant seizures (1 concurrent AED or <4 lifetime AEDs) at baseline. For each subgroup, median percent reduction in POS frequency (primary endpoint), responder rate, Clinical Global Impression of Change (CGI-C), and Quality of Life in Epilepsy--Problems (QOLIE-31-P) survey were assessed. Of 249 PREVAIL patients, 115 were classified as having highly drug-resistant seizures (USL255: n = 52, placebo: n = 63), and 134 were classified as having less drug-resistant seizures (USL255: n = 72, placebo: n = 62) at baseline. For the primary endpoint, USL255 resulted in significantly better seizure outcomes compared with placebo regardless of drug-resistant status (P = .004 and P = .040 for "highly" and "less", respectively). Responder rate was also significantly improved in patients with highly drug-resistant group (P = .023). The CGI-C scores indicated significant improvement in both subgroups (P = .003 and P = .013 for "highly" and "less", respectively). On the QOLIE-31-P, a significant improvement on the seizure worry subscale for the group with less drug-resistant seizures was noted in USL255-treated patients compared with placebo-treated patients (P = .003); the overall score and all other subscales were not significantly different for both subgroups. We conclude that USL255 led to significant improvements across multiple outcomes compared with placebo, including in those classified as having highly drug-resistant seizures to prior treatment, making it a valuable treatment option for patients with epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Delayed-Action Preparations; Double-Blind Method; Drug Resistance; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Seizures; Topiramate; Treatment Outcome; Young Adult

We conducted a post hoc assessment of the effect of ≥6 months of topiramate monotherapy on height in pediatric patients with newly diagnosed partial-onset seizure. Data on height measured nonsystematically up to 4 years from two randomized, double-blind studies and their open-label extensions were combined and converted to z scores and percentiles by patient's sex and age. Height velocity values (centimeters per year) and the associated z scores were computed for each postbaseline year using normative data. Median height velocity (centimeters per year) values and the associated z scores for patients ages 6-9 years were, year 1: 4.7 (-0.91); year 2: 4.2 (-1.62); year 3: 4.5 (-1.87); and for patients ages 10-15 years were, year 1: 4.0 (-0.76); year 2: 2.8 (-1.34); year 3: 3.1 (-0.74). There was a significant correlation between height velocity z score and change from baseline in height z score (r = 0.94 [n = 117]; P < 0.0001). Patient's bicarbonate status (low was defined as two postbaseline serum bicarbonate values <20 mmol/L) and sex had no effect on height velocity. In both age groups, continued growth was observed; however, the growth rate was slower than expected compared with a matched normal population from years 1 to 2 and showed minimal recovery from years 2 to 3.

Topics: Adolescent; Anticonvulsants; Bicarbonates; Body Height; Child; Double-Blind Method; Epilepsies, Partial; Female; Follow-Up Studies; Fructose; Growth; Humans; Male; Sex Characteristics; Topiramate

Topiramate was used in the treatment of 66 children, aged 2--16 years (mean age 7.0±4.6 years), including 19 patients with idiopathic form of focal epilepsy (IFE), 21 patients with cryptogenic forms (CFE) and 26 patients with symptomatic forms (SFE). The drug was administered in capsules in dose from 3 to 7 mg/kg/day. Thirty-three patients were on monotherapy, 26 patients received the drug in the combination with one antiepileptic (AED) drug and 7 patients received topiramate in the combination with 2 AEDs. The efficacy of topiramate in focal epilepsy was demonstrated in 65% of patients, including high efficacy in 15% and complete reduction of seizures in 12%. No effect was seen in 27% of patients. The results revealed the high efficacy of topiramate in all subgroups of patients. The significantly higher efficacy was noted in patients with IFE and CFE forms compared to those with SFE form. The tolerability was satisfactory in all subgroups. Side-effects observed in 5 patients were eliminated by increasing the duration of dose titration.

Topics: Adolescent; Anticonvulsants; Capsules; Child; Child, Preschool; Drug Combinations; Epilepsies, Partial; Female; Fructose; Humans; Male; Topiramate; Treatment Outcome

To characterize the pharmacokinetics of adjunctive topiramate in infants (1-24 months) with refractory partial-onset seizures (POS); also to evaluate safety and tolerability of topiramate in the dose range of 3-25 mg/kg/day.. In this open-label phase 1 study, infants (N = 55) with refractory POS receiving at least one concurrent antiepileptic drug (AED) were enrolled. Infants were stratified by age and randomly assigned to one of four topiramate target dose groups (3-, 5-, 15-, or 25 mg/kg/day). Treatment was initiated at 3 mg/kg/day with titration to the target dose by weekly dose escalation. Topiramate was administered daily in two divided doses as oral liquid (5 mg/ml for infants <9 kg or those who could not tolerate solid foods) or sprinkle capsule (25 mg) formulations. Following seven consecutive days of topiramate administration at the target dose, four blood samples were collected from each infant for pharmacokinetic assessments (predose, 1-3, 4-6, and 8-10 h postdose).. Fifty-five infants (mean [SD] age in months: 11.4 [5.79]) with POS were enrolled, of whom 33% had seizures with or without secondary generalization. Complete pharmacokinetic profiles were obtained in 35 infants in whom mean plasma topiramate concentration-time profiles demonstrated linear pharmacokinetics (predose topiramate concentrations [C(trough) ] and area under the plasma concentration-time curve from time 0 through 12 h [AUC(12 h)]) of topiramate over the dose range studied). Apparent steady state oral clearance (CL(ss) /F) remained similar across all topiramate target dose groups and was independent of creatinine clearance, age, and weight. Mean values for CL(ss) /F were approximately twofold greater in infants receiving concomitant enzyme-inducing AEDs versus enzyme-inhibiting AEDs. Topiramate was well tolerated and safety findings were consistent with previous reports in children and adults. Most common treatment emergent adverse events (≥10%) were upper respiratory tract infection, fever, vomiting, somnolence, and anorexia.. In infants (1-24 months), topiramate exhibited linear steady state pharmacokinetics over the dose range 3-25 mg/kg/day, and CL(ss) /F of topiramate was independent of dose. Moreover, the concomitant enzyme-inducing AEDs doubled the clearance of topiramate. Topiramate was generally well tolerated as adjunctive therapy at doses up to 25 mg/kg/day.

Topics: Anticonvulsants; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Infant; Infant, Newborn; Male; Topiramate

Epilepsy is a heterogeneous disorder, with outcomes ranging from immediate remission after taking a first antiepileptic drug to frequent unremitting seizures with multiple treatment failures. Few prognostic models enable prediction of outcome; we therefore aimed to use data from the SANAD study to predict outcome overall and for patients receiving specific treatments.. The SANAD study was a randomised controlled trial in which standard antiepileptic drugs were compared with new treatments. Arm A included patients for whom carbamazepine was considered the first-line treatment, most of whom were newly diagnosed with focal epilepsy. Patients were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Outcomes were time to treatment failure overall, because of inadequate seizure control, and because of adverse events, and time to 12 months of remission from seizures. In this post-hoc study we used regression multivariable modelling to investigate how clinical factors affect the probability of treatment failure and the probability of achieving 12 months of remission.. For time to treatment failure, we identified several significant risk factors: sex (male vs female, hazard ratio [HR] 0·86, 95% CI 0·75-0·99), treatment history (taking non-SANAD antiepileptic drugs [other than those listed above] vs treatment naive, 1·27, 1·05-1·53), age (eg, older than 71 years vs 10 years or younger, 0·68, 0·51-0·91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1·08, 1·05-1·11), electroencephalogram results (epileptiform abnormality vs normal, 1·26, 1·07-1·50), seizure type (eg, secondary generalised vs simple or complex partial only, 0·78, 0·66-0·91), site of onset (not localised vs temporal lobe, 1·25, 1·06-1·47), and treatment (lamotrigine vs carbamazepine, 0·76, 0·61-0·95). Significant factors for time to 12 months of remission were sex (male vs female, 1·19, 1·05-1·35), treatment history (taking a non-SANAD antiepileptic drug vs treatment naive, 0·64, 0·52-0·78), age (eg, older than 71 years vs 10 years or younger, 1·60, 1·26-2·03), time from first seizure (60-239 months vs ≥2 months, 1·14, 1·01-1·29; >240 months vs ≤2 months, 1·39, 1·04-1·86), neurological insult (present vs absent, 0·75, 0·61-0·93), total number of seizures before randomisation (eg, four to 11 vs two or fewer, 0·87, 0·85-0·90), and treatment (gabapentin vs carbamazepine, 0·71, 0·59-0·86; topiramate vs carbamazepine, 0·81, 0·68-0·98).. We present a thorough investigation of prognostic factors from a large randomised controlled trial in patients starting antiepileptic monotherapy. If validated, our models could aid in individual patient risk stratification and the design and analysis of epilepsy trials.. National Institute for Health Research (UK).

Topics: Adolescent; Adult; Aged; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Disease-Free Survival; Epilepsies, Partial; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Middle Aged; Oxcarbazepine; Prognosis; Time Factors; Topiramate; Treatment Failure; Triazines; Young Adult

To compare the tolerability and efficacy of two titration methods (rapid and slow titration) for TOPINA Tablets with different dosages and periods of escalation, a double-blind comparative study was conducted in patients with localization-related epilepsy. A total of 183 patients were randomized to either rapid titration (initial dosage 100 mg/day increased by 100-200 mg at weekly intervals) or to slow titration (initial dosage 50 mg/day increased in 50 mg/day increments at weekly intervals). TOPINA Tablets were administered for 12 weeks to the maximum dosage of 400 mg/day. The incident of adverse events leading to treatment interruptions or withdrawals was 18.9% in rapid titration and 14.8% in slow titration, with no statistical significance (p = 0.554). The incident of adverse events and adverse reactions of slow titration was slightly lower than that of rapid titration. The common adverse events and adverse reactions reported in the two titration methods were comparable and were well tolerated. On the other hand, the efficacy of slow titration, percent reduction in seizure rate and responder rate, was comparable with that of rapid titration. In conclusion, there were no significant differences of therapeutic response to TOPINA Tablets between the two titration methods.

Topics: Adolescent; Adult; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Seizures; Tablets; Topiramate; Treatment Outcome; Young Adult

The effects of topiramate (TPM) were evaluated in 51 patients with intractable epilepsy. Callosotomy and hemispherotomy were performed in 16 patients and one patient before the administration of TPM, respectively. The 50% responder rate (50%RR) was recorded in 39% of the total patient population and in 58% of patients with symptomatic location-related epilepsy (SLE). TPM was most effective for frontal lobe epilepsy (FLE), and the 50%RR was recorded in 88% of those patients. TPM (50%RR) was more effective in secondary generalized seizures (in 75%) and complex partial seizures (in 67%) in comparison to that of tonic-clonic seizures (in 44%) and drop attacks (in 29%). Seventy-one percent of the patients with atypical absence seizures increased seizure frequency. The 50%RR was recorded in 22% of the patients who underwent epilepsy surgery, and 29% of those patients also showed seizure aggravation due to TPM. These results suggest the efficacy of TPM for intractable epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Epilepsy, Frontal Lobe; Epilepsy, Generalized; Female; Fructose; Humans; Infant; Male; Topiramate; Treatment Outcome; Young Adult

This double-blind, placebo-controlled study investigated the efficacy and tolerability of adjunctive topiramate in 86 elderly Chinese patients with refractory partial epilepsy. Patients who had at least four seizures per 4 weeks during an 8-week baseline period, despite medication with up to three standard antiepileptic drugs (AEDs), were randomly assigned to receive topiramate (n = 46) or placebo (n = 40). Topiramate dosages were titrated (target dose 200 mg/day orally) for 8 weeks and maintained at stable levels for another 12 weeks; concomitant AEDs continued at original dosages. All patients completed the study: 47.8% in the topiramate group and 7.5% on placebo reached ≥ 50% reduction in complex partial seizures. In the topiramate group, the most common adverse events were dizziness, somnolence, fatigue, headache and difficulty with memory; most events were transient and mild or moderate in severity. It was concluded that 200 mg/day topiramate was effective and well-tolerated in elderly patients with refractory partial epilepsy.

Topics: Administration, Oral; Aged; Anticonvulsants; Asian People; China; Epilepsies, Partial; Female; Fructose; Humans; Male; Seizures; Topiramate

An aim was to study the efficacy of different groups of antiepileptic drugs in the treatment of focal symptomatic (or probably symptomatic) epilepsy in children. The study included 96 patients, aged from 1 month to 17 years, 55 boys and 41 girls. They were stratified into three groups by drug type: group 1 (34 patients) was treated with phenobarbital, group 2 (31 patients) received topiramate and group 3 (31 patients) received lamotrigine. It has been shown that antiepileptic drugs of the new generation have higher efficacy with regard to focal forms of epilepsy in children compared to phenobarbital. However therapeutic effect, especially regarding seizure frequency, was specific for each drug.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Infant; Infant, Newborn; Lamotrigine; Male; Phenobarbital; Topiramate; Treatment Outcome; Triazines

A clinical trial included 30 children, aged from 24 to 46 months, stratified into two groups on the basis of clinical-instrumental data: 22 (73%) patients with symptomatic focal epilepsy and 8 (27%) patients with cryptogenic (possibly symptomatic) focal epilepsy. Topamax (topiramate) was used as mono- (8 children) and combined (22 children) therapy. Mean treatment dose was 5,9 mg/kg per day. Efficacy of treatment was evaluated by the changes in frequency of seizures. After 6 months, the positive result (completed stopping of seizures or their reduction by 50% and more) was seen in 19 (63,75%) patients. The effect was absent or was minimal in 9 (29,5%). In 2 (6,75%) cases the frequency of seizures increased. Adverse events were recorded in 11 (36%) patients, side-effects that led to the treatment discontinuation (vomiting, increasing of seizure frequency, enuresis) were found in 5 (16%) patients.

Topics: Anticonvulsants; Child, Preschool; Epilepsies, Partial; Female; Fructose; Humans; Infant; Male; Topiramate; Treatment Outcome

The aim of the present work was to perform a comparative assessment of the efficacy and safety of traditional and contemporary antiepileptic agents in women of reproductive age. The experimental group consisted of 65 patients, of whom 48 had partial epilepsy and 17 had idiopathic generalized epilepsy. A number of issues were addressed in studies of a larger group of patients (110), including both women (65) and men (45). The following agents were studied: Topamax, valproates, carbamazepine, and barbiturates, all used as monotherapy. Patients' status was evaluated using clinical (neurological, psychiatric), psychometric, neuropsychological, and hormonal parameters. The data led to the general conclusion that Topamax had advantages over the other study agents in the treatment of women with epilepsy.

Topics: Adult; Anticonvulsants; Barbiturates; Carbamazepine; Epilepsies, Partial; Epilepsy, Generalized; Estradiol; Female; Fructose; Humans; Male; Mental Disorders; Neuropsychological Tests; Psychiatric Status Rating Scales; Severity of Illness Index; Sex Characteristics; Testosterone; Topiramate; Treatment Outcome; Valproic Acid

To evaluate the efficacy and safety of adjunctive topiramate (sprinkle capsules or oral liquid) in reducing daily rates of partial-onset seizures (POS) in infants with refractory POS.. In this double-blind, placebo-controlled, parallel-group, international study, infants (n = 149) with clinical or EEG evidence of refractory POS were randomly allocated (1:1:1:1) to receive adjunctive topiramate 5, 15, or 25 mg/kg/d or placebo for 20 days. The primary variable was the median percentage reductions in daily POS rate from baseline to final assessment as recorded on a 48-hour video-EEG.. Of the 149 infants (mean age 12 months) included in the intent-to-treat analysis set, 130 completed the study. Median percentage reduction from baseline in daily POS rate was not significantly different (p = 0.97) between topiramate 25 mg/kg (20.4%) and placebo (13.1%). Lower doses were not formally tested, but nominal p values for comparisons with placebo were not significant (15-mg/kg/d dose: p = 0.97; 5-mg/kg/d dose: p = 0.91). Treatment-emergent fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infection occurred more frequently (> or = 10% difference) with topiramate than with placebo.. In infants aged 1-24 months, topiramate 5, 15, or 25 mg/kg/d was not effective as adjunctive treatment for refractory partial-onset seizures. No new safety concerns associated with topiramate use were noted.. This interventional study provides Class I evidence that topiramate 5, 15, or 25 mg/kg/d compared with placebo does not significantly reduce seizure rates in infants aged 1 month to 2 years with refractory partial-onset seizures.

Topics: Anticonvulsants; Brain; Chemotherapy, Adjuvant; Double-Blind Method; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Infant; Male; Seizures; Topiramate; Treatment Outcome; Video Recording

For a retrospective observational investigation based on real clinical practice of relative efficacy of valpoic acid (VPA), carbamazepine (CBZ) and topiramate (TPM) we have selected 106 patients with age of seizure onset before 17 years with a undoubted diagnosis of symptomatic or cryptogenic occipital lobe epilepsy (OLE), who had received treatment according to ILAE recommendations, and observation time since the last treatment change was from 2 to 10 years. Patients suspicious for idiopathic epilepsies were excluded. The groups of patient receiving CBZ, VPA and TPM did not differ significantly in presenting unfavorable prognostic factors and dose regimes that allowed to conduct direct comparison of efficacy of the investigated drugs. Efficacy of VPA in children with OLE was higher compared with CBZ (69% vs 36%, p < 0.01) and TPM (69% vs 8%, p < 0.001). CBZ and TPM caused seizure aggravation more frequently than VPA (12% and 13% respectively vs 1%, p < 0.001). In case of presence of clinico-electroencephalografic and MRI signs of significant organic brain damage and in patients with seizure onset under 11 years TPM was not effective. In case of focal cortical dysphasia the efficacy of CBZ was lower than VPA (20% vs 63%, p < 0.05). In MRI-negative cases VPA was most effective (79% vs 44% for CBZ, p < 0.001 and 29% for TPM, p < 0.01). Efficacy of CBZ and TPM reduces proportionally the number of previously used antiepileptic drugs (AEDs), this tendency is noted also for VPA but as a second AED it was more effective than CBZ and TPM (56% vs 15%, p < 0.01 and 14%, p < 0.05, respectively); as a first AED VPA was also most effective (82% vs 37%, p < 0.001 for CBZ and 82% vs 33%, p < 0.01 for TPM). Adverse effects were more frequent during treatment with CBZ and TPM, than VPA (21% vs 6%, p < 0.001 and 17% vs 6%, p < 0.05).

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Brain Injuries; Carbamazepine; Child; Epilepsies, Partial; Epilepsy; Fructose; Humans; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Valproic Acid

Clinicians monitor cognitive effects of drugs primarily by asking patients to describe their side effects. We examined the relationship of subjective perception of cognition to mood and objective cognitive performance in healthy volunteers and neurological patients.. Three separate experiments used healthy adults treated with lamotrigine (LTG) and topiramate (TPM), adults with epilepsy on LTG or TPM, and patients with idiopathic Parkinson's disease. Correlations were calculated for change scores on and off drugs in the first two experiments and for the single assessment in Experiment 3.. Across all three experiments, significant correlations were more frequent (chi(2)=259, P < or = 0.000) for mood versus subjective cognitive perception (59%) compared with subjective versus objective cognition (2%) and mood versus objective cognitive performance (2%).. Subjective perception of cognitive effects is related more to mood than objective performance. Clinicians should be aware of this relationship when assessing patients' cognitive complaints.

Topics: Adult; Affect; Anticonvulsants; Cognition; Cross-Over Studies; Depression; Double-Blind Method; Epilepsies, Partial; Female; Fructose; Humans; Lamotrigine; Male; Neuropsychological Tests; Parkinson Disease; Psychomotor Performance; Quality of Life; Self Concept; Topiramate; Triazines

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 objective of this observational study was to compare the efficacy of levetiracetam and topiramate during the first 15 days of add-on treatment in adults with refractory partial epilepsy. Two cohorts of patients with > or =3 simple or complex partial seizures with or without secondary generalisation per month over an 8-week baseline period received levetiracetam or topiramate in two distinct phases, in addition to standard antiepileptic treatment. During the first 15 days of the therapy, levetiracetam was added at the dosage of 250 mg b.i.d. or topiramate at 25mg o.i.d. Efficacy parameters included number of seizure-free days (SFDs), mean and percent reduction in seizure frequency (in general and by type), and number of seizure-free patients in the first 15 days of treatment compared to last 15 days of the baseline period. Sixty-one patients received levetiracetam and 61 topiramate. The general characteristics of the two treatment groups were similar. The total number of SFDs during 15 days before treatment was 637 with levetiracetam and 621 with topiramate; in the 15-day evaluation period the SFDs increased to 748 (17.4%) and 668 (7.6%), respectively (ANOVA, p<0.05). Twenty-six patients (42.6%) taking levetiracetam were seizure free compared to 10 (16.4%) receiving topiramate (chi-square, p=0.003). This open-label non-controlled study suggests an early efficacy of levetiracetam as add-on therapy in patients with refractory partial epilepsy: these results appear to confirm previous indications of a rapid onset of action and seem to suggest first evaluation of the patient at the dose of 500 mg/day before increasing to the considered minimum standard dose of 1000 mg/day, as some patients could respond to the starting dose.

Topics: Adolescent; Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Topiramate; Treatment Outcome

An open, prospective, observational study was performed to assess efficacy and adverse-event profile of topiramate as add-on therapy in epilepsy. Outpatient neurology clinics from 11 general hospitals in Greece participated in the study. In total, 211 patients with treatment resistant partial-onset seizures who met the inclusion criteria, were studied. After baseline evaluation, topiramate was given at a target dose of 200mg/day over a 1-month titration period. In the subsequent maintenance period, the topiramate dose could be varied according to the clinical results. Patients were followed for in total 6 months, with monthly visits and regular physical, neurological and laboratory examinations. Seizure frequencies decreased to 35--40% of baseline values following 3 months of treatment and remained relatively constant thereafter. The average monthly seizure frequency over the 6-month study period was 4.61, compared to 9.21 at baseline. The number of responders (patients with at least 50% reduction in seizure frequency) followed a similar pattern, i.e., increase during the first 3 months levelling off at a final 80--85% response rate. Of those completing the study, 30% had been seizure-free for at least 3 months and 12% for 5 months. Topiramate was well tolerated, no deviations in laboratory values were found. Adverse events appeared to occur less frequently, and antiepileptic effects were more pronounced in this prospective open-label study than in earlier reports from randomised controlled trials. The nature of the patient population and the application of individualised dose optimisation are proposed as contributing factors to explain the favourable results of this study.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Hospitals, General; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Prospective Studies; Topiramate

To evaluate the effects of topiramate (TPM) on interictal epileptiform abnormalities (IEA) and background activity by means of a computerized EEG analysis, in adult patients affected by focal epilepsy, with or without secondarily generalization, treated with TPM as adjunctive therapy or monotherapy.. Twenty-four patients affected by symptomatic or cryptogenic focal epilepsy underwent long-term video-EEG recording before and after TPM addition (mean dose 175+/-25 mg per day).. TPM addition induced a significant reduction of both partial and secondarily generalized tonic-clonic (SGTC) seizures; treatment responder patients (seizure reduction > or = 50%) were 19 out of 24 patients (79.1%), of whom 5 were seizure-free. Quantitative analysis of IEA showed a significant decrease in the mean number of spikes/10 min during TPM therapy ( 4.2+/-4.2 versus 2.2+/-4.4; P<0.003 ). The analysis of spatial distribution of interictal spikes showed that such reduction was more evident at the level of the epileptogenic area rather than on the spreading component. Statistical analysis revealed only a significant decrease of mean relative power of alpha band in the EEG spectral content, recorded at rest in a group of 18 out of 24 epileptic patients during TPM therapy. In addition, during TPM treatment we observed a significant reduction in alpha reactivity without any important changes of alpha indexes (peak frequency and median frequency).. These findings suggest that TPM has a strong inhibitory effect on IEA, probably acting on the generating processes, and, if used at low dosage and gradually titrated, seems to have only mild interferences with EEG background activity.

Topics: Adolescent; Adult; Analysis of Variance; Anticonvulsants; Brain Mapping; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; 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

To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study.. Adults and children (>/=3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Epilepsies, Partial; Fatigue; Female; Fructose; Headache; Humans; Male; Middle Aged; Paresthesia; Proportional Hazards Models; Topiramate; Treatment Outcome

Cognitive effects have been reported during topiramate (TPM) treatment, but effects relative to standard antiepileptic drugs are unclear.. The authors compared TPM and valproate (VPA) added to carbamazepine (CBZ) in adults with partial seizures. A comprehensive neuropsychological test battery including cognitive, mood, and quality of life measures was used in this multicenter, randomized, double-blind study. After a 4-week baseline, study drug was titrated over 8 weeks to target dosages of 400 mg/d TPM, 2,250 mg/d VPA, or placebo and then maintained for an additional 12 weeks. The neuropsychological test battery was administered at baseline and at the end of titration and maintenance periods.. Slightly more patients on TPM dropped out. Neuropsychological data at all three test periods were available for 62 patients. At the end of maintenance, effects of TPM and VPA were comparable, except for two variables (Symbol Digit Modalities Test and Controlled Oral Word Association Test), in which TPM had greater negative effects relative to VPA. The statistical differences appeared to be due in large part to a small subset of patients who were more negatively affected by TPM. Cognitive effects of TPM relative to VPA were greater at the end of titration than at the end of maintenance.. With adjunctive therapy at moderate dose escalation rate, the cognitive effects of TPM are slightly worse overall than VPA in patients who tolerate therapy over several months.

Topics: Adolescent; Adult; Affect; Anticonvulsants; Attention; Behavior; Carbamazepine; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Memory; Middle Aged; Neuropsychological Tests; Psychomotor Performance; Quality of Life; Topiramate; Valproic Acid

Twenty-five epileptic patients, mean age 25.7 years, have been studied. Twenty-two of them were diagnosed with symptomatic partial epilepsy, 1--with criptogenic partial epilepsy and 2--with idiopathic partial epilepsy. Illness duration was estimated as follows: above 5 years--5 patients, above 10 years--10, above 20 years--4 and less than 5 years--6. Polymorphic seizures were detected in 56% of the cases and monomorphic ones, resistant to the previous traditional anticonvulsant therapy,--in 44%. Topamax was used as an add-on therapy to the previously prescribed anticonvulsants in initial dose of 25 mg daily, with a following continuous dose increase. The mean therapeutic dosage was 100 mg daily. Therapeutic efficacy was assessed during 3 months. Since 1 month of topamax adjunction to a treatment schedule, a mean frequency of all types of seizures was reduced. The best effect was found in the case of combination of simple partial and secondary generalized seizures. The medication was effective in 60-80% of the patients with strong resistance to traditional anticonvulsants. Topamax is concluded to be a highly effective antiepileptic medication, which gives new possibilities for a treatment of patients with partial epilepsy resistant to traditional drugs.

Topics: Adolescent; Adult; Anticonvulsants; Child; Drug Resistance; Epilepsies, Partial; Female; Fructose; Humans; Male; Topiramate

To establish the concentration response of topiramate in patients with refractory focal epilepsy.. Sixty-five patients with more than eight seizures during an 8-week baseline were randomized to three prespecified plasma levels (low, 6 micromol/L [2 mg/L]; medium, 31 micromol/L [10.5 mg/L]; and high, 56 micromol/L [19 mg/L]). Topiramate treatment was titrated to one of the prespecified plasma levels during an 8-week titration period, followed by a 12-week observation period.. The overall median (25th to 75th percentile) reduction in seizures during the observation compared with baseline was 50% (9.5 to 90%). In the individual groups, the median reduction was as follows: low, 39% (13 to 70%); medium, 85% (41 to 96%); and high, 39% (2.0 to 81%). The primary outcome of the trial was the comparison of seizure reduction (Mann-Whitney U test) between the low and the medium group (p = 0.03). Comparisons between the other groups were as follows: medium vs high (p = 0.05) and low vs high (p = 0.81). Psychiatric adverse events and adverse events related to the CNS were the most frequently encountered. Most adverse events showed concentration response, particularly between low and medium levels.. Patients assigned to the medium plasma level (31 micromol/L [10.5 mg/L]) had the best seizure outcome. Patients in the medium and high groups experienced more adverse events than patients in the low group. Optimal treatment response is thus most likely found at plasma concentrations higher than 6 micromol/L (2 mg/L), but no further increase in efficacy seems to occur at concentrations above 31 micromol/L (10.5 mg/L).

Topics: Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Safety; Seizures; Topiramate; Treatment Outcome; Vertigo

Based on dose predictions from animal and human volunteer studies, most patients enrolled in initial randomized controlled trials of topiramate as adjunctive therapy in adults with partial-onset seizures were randomized to >or= 600 mg/day topiramate. Subsequent experience suggests that dosage needs were overestimated. This double-blind, placebo-controlled study evaluated 200 mg/day topiramate in adults with treatment-resistant partial-onset seizures receiving a concurrent enzyme-inducing antiepileptic agent (carbamazepine).. After a 4-week baseline, 263 adults receiving carbamazepine who had at least three partial-onset seizures during the baseline period were randomized to placebo or one of two topiramate 200 mg/day treatment arms: topiramate escalated weekly 25 mg/day(8-week escalation) or 50 mg/day(4-week escalation). Therapy was then maintained for the remainder of the 12-week double-blind study.. Median percent reduction in seizure frequency from baseline to study end was 44% with topiramate and 20% with placebo (P or=10% incidence in topiramate-treated patients) were somnolence, fatigue, paresthesia, nervousness and anorexia; 8% of topiramate-treated patients and 2% of placebo-treated patients discontinued because of adverse events. As a result of the low incidence of adverse events, differences between titration rates in terms of tolerability were not detected.. Topiramate 200 mg/day is an appropriate target dose as adjunctive therapy in adults with treatment-resistant partial-onset seizures, even when receiving an enzyme-inducing agent; 100 mg/day also appears to be effective. A significant therapeutic effect may be seen in the second week of treatment with a dose of 100 mg/day.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Topiramate; Treatment Outcome

This study was to evaluate the efficacy and safety of topiramate (TPM) in refractory partial epilepsy in children, adolescents and young adults.. We performed a prospective open label add-on study in 55 patients (age 2-30 years, mean 15 years) with refractory partial seizures. Topiramate was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency.. TPM was initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24h, up to a maximum daily dose of 12 mg/kg. After 9 months of treatment, 11 patients (20%) had 100% fewer seizures and 25 patients (45%) had a more than 50% seizure reduction. TPM appeared to be effective both in cryptogenic (76.2%) and symptomatic (58.8%) partial epilepsies. Mild to moderate adverse events were present in 25 patients (45.4%), mostly represented by drowsiness, nervousness and hyporexia with or without weight loss.. TPM was an overall effective and safe add-on drug both in cryptogenic and symptomatic childhood refractory partial seizures, the adverse reactions being generally mild or moderate.

Topics: Adolescent; Adult; Child; Child, Preschool; Epilepsies, Partial; Female; Fructose; Humans; Male; Neuroprotective Agents; Prospective Studies; Psychoses, Substance-Induced; Topiramate; Weight Loss

Intensive and quantitative evaluation of the severity and frequency of seizures and ictal signs during topiramate (TPM) treatment.. Twenty patients with refractory partial seizures 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. Study phases included a 3-day baseline video-EEG phase, a 10-day TPM titration phase without video-EEG and a 3-day 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: duration (lasting seconds of each seizure and ictal sign), intensity (on a 0-3 scale), N/24 h (numbers of attacks per 24 h), D/24 h (duration per 24 h) of both seizures and defined ictal signs.. A total of 399 seizures during the baseline phase and the dose maintenance phase were intensively analyzed. Intergroup comparison suggested that duration, N/24 h and D/24 h of all seizures 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, intensity and N/24 h of ictal signs like hypermotoric movements, fumbling and vocalization in the medium dosage group (P<0.05).. Topiramate has an early dose-dependent effect on ictal seizures.. The present study intensively analyzed the duration, intensity, N/24 h and D/24 h of ictal seizure manifestations. The quantitative data suggested that topiramate had an early effect on ictal phenomena like ictal hypermotoric movements, fumbling and vocalization (P<0.05); effects were more prominent in the medium dosage group (200 mg daily) than the low dosage group (100 mg daily).

Topics: Adolescent; Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Statistics, Nonparametric; Topiramate

Twenty patients of either sex, with refractory partial epilepsy with or without secondary generalisation were entered in an open label study to evaluate the efficacy and safety of topiramate in them. Topiramate was used as an adjunctive therapy with an initial starting dose of 50 mg/day. The dose was then titrated upwards with increments of 50 mg per week, till a time the most effective and the best tolerated dose was reached. This most effective/tolerated dose was then continued for 6 months. Of the 17 patients entering the maintenance phase, 4 patients (24%) became seizure free, while a total of 14 patients (83%) out of 17 cases responded with a reduction in monthly seizures rate by 50% or more. Mean reduction of 68.9% was observed in monthly seizure rate during the maintenance phase. The median effective dose of topiramate was 600 mg per day. Five patients dropped out of the study due to adverse events such as anxiety, aggressiveness, rash, lethargy, etc. The central nervous system (CNS) related side effects such as dizziness, headache, and tremor were reported, which are commonly seen with other presently available antiepileptics like carbamazepine, phenytoin sodium, sodium valproate, etc, as well. Most adverse events, however, were mild and transient and did not interfere with the day to day activity of the patients. Topiramate was not associated with any abnormality in laboratory or neurological examination findings. The excellent response with topiramate therapy in Indian patients, uncontrolled with the available antiepileptics, as well as its good safety profile endorse the international efficacious and safe image of topiramate.

Topics: Adolescent; Adult; Anticonvulsants; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsies, Partial; Female; Follow-Up Studies; Fructose; Humans; India; Male; Topiramate; Treatment Outcome

A total of 292 adult patients (mean age, 33 years) with partial and/or generalized seizures previously resistant to antiepileptic drug (AED) therapy (median baseline seizure rate, 12 seizures/month) were treated with open-label topiramate (TPM) in dosages of 100-1,600 mg/day.. The mean duration of TPM treatment was 413 days (range, 84-804 days), and the mean TPM dosage was 503 mg/day (range, 100-1,600 mg/day; median TPM dosage, 300 mg/day). Seizure reduction was calculated from seizure counts during the last 3 months and last 6 months of TPM therapy compared with baseline.. Overall, >50% of patients achieved > or =50% seizure reduction. More important, 11% of patients were seizure-free for > or =3 months at the last visit; 10% of patients were seizure free for > or =6 months at the last visit. This robust therapeutic response was consistent for patients receiving TPM dosages >400 and <400 mg/day. The most commonly reported adverse events were related to the central nervous system. Over the 2.2-year treatment period, 19% of patients discontinued TPM therapy because of inadequate seizure control; 32% discontinued because of adverse events. Findings from this study show that TPM is a useful agent for long-term seizure control, with some patients becoming seizure free for extended periods despite failing previous AED therapy.

Topics: Adolescent; Adult; Aged; Anorexia; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fatigue; Female; Fructose; Headache; Humans; Incidence; Male; Middle Aged; Placebos; Sleep Wake Disorders; Topiramate; Treatment Outcome; Weight Loss

Children with partial-onset seizures, with or without secondary generalization, participating in a double-blind, placebo-controlled trial of topiramate (TPM) as adjunctive therapy were eligible to participate in an open-label, long-term extension study.. A total of 83 children (mean age, 9 years) continued long-term open-label TPM therapy in which the dosages of TPM and concomitant antiepileptic drugs (AEDs) were adjusted according to clinical response (mean TPM dosage, 9 mg/kg/day).. Seizure frequency over the last 3 months of therapy was reduced > or =50% in 57% of children; 14% of children were seizure-free > or =6 months at the last visit. During treatment periods up to 2 1/2 years (mean, 15 months), 6% of children discontinued because of treatment-emergent adverse events; 13% discontinued because of inadequate seizure control.. From these findings, TPM is well tolerated and provides long-term seizure control in children with partial-onset seizures.

Topics: Adolescent; Age Factors; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Fructose; Humans; Placebos; Severity of Illness Index; Topiramate; Treatment Outcome

The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study.. A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial.. In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group.. TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dizziness; Double-Blind Method; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Placebos; Topiramate; Treatment Outcome; Weight Loss

This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerability and prevents cognitive impairment.. The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach.. For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration.. Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Cognition; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Placebos; Psychomotor Performance; Topiramate; Treatment Outcome; Valproic Acid

To evaluate the efficacy and safety of topiramate 6 mg/kg/day in children (age 2 to 16 years) as adjunctive therapy for uncontrolled partial-onset seizures with or without secondarily generalized seizures in a multicenter, randomized, double-blind, placebo-controlled trial.. Patients with at least six partial-onset seizures during the 8-week baseline phase were treated with either topiramate (n = 41) or placebo (n = 45) for 16 weeks.. Topiramate-treated patients had a greater median percent reduction from baseline in average monthly partial-onset seizure rate than placebo-treated patients (33.1% versus 10.5%, p = 0.034), a greater proportion of treatment responders (i.e., patients with a > or = 50% seizure rate reduction; 16 of 41 [39%] versus 9 of 45 [20%], p = 0.080), and patients with a > or = 75% seizure rate reduction (7 of 41 [17%] versus 1 of 45 [2%], p = 0.019), and better parental global evaluations of improvement in seizure severity (p = 0.019). Emotional lability (12% versus 4%), fatigue (15% versus 7%), difficulty with concentration or attention (12% versus 2%), and forgetfulness/impaired memory (7% versus 0%) were more frequent among topiramate-treated than placebo-treated patients. Most treatment-emergent adverse events were mild or moderate in severity. No topiramate-treated patients discontinued the study due to adverse events.. Topiramate was safe and effective in the treatment of partial-onset seizures in children.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Epilepsies, Partial; Female; Fructose; Humans; Infant; Male; Topiramate

To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies.. We used a multicenter double-blind placebo-controlled randomized parallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of stabilization phase. The primary efficacy variable was the median seizure frequency reduction rate (MSFRR), and the other efficacy variables included responder rate, seizure-free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 50 mg/day and gradually increased to the target dose over a 10-week period.. A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who were randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were available for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001). Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation greatly favored TPM (p = 0.001). The incidence of adverse events (AEs) was higher in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) patients taking TPM and three (3.5%) patients taking PLC. No serious systemic AEs were observed.. TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM might be responsible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites.

Topics: Abdominal Pain; Anorexia; Anticonvulsants; Central Nervous System Diseases; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Humans; Incidence; Korea; Placebos; Topiramate; Treatment Outcome

Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.. A total of 48 patients were evaluated in a double-blind, parallel-group trial. During a 56-day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs). After 1-2 weeks of open-label treatment with TPM 100 mg/day, patients were randomly assigned, in equal proportions, to receive double-blind therapy with TPM 100 or 1,000 mg/day in a 5-week conversion and an 11-week monotherapy period. The study endpoint was completion of 112 study days (success) or fulfillment of one or more exit criteria: doubling of average 28-day or highest 2-day baseline seizure rate, a generalized tonic-clonic seizure (GTCS) if none had occurred at baseline, or significant prolongation of generalized seizure duration.. Time until exit was longer (p = 0.002) and success frequency was higher (p = 0.005) with TPM 1,000 as compared with 100 mg/day. Seizure-rate reductions of > or = 50, > or = 75, or 100% were achieved by 46, 25, and 13% of the 1,000-mg/day group, respectively, as compared with 13, 8, and 0% of the 100-mg/day group, respectively. Most adverse events (AE) were mild or moderate in severity.. Monotherapy with TPM 1,000 mg/day for partial onset seizures with or without secondarily generalized seizures was effective, with a favorable safety profile.

Topics: Adult; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Female; Fructose; Humans; Male; Paresthesia; Placebos; Topiramate; Treatment Outcome

In companion double-blind, placebo-controlled, dose-ranging trials performed in the United States, topiramate (TPM) daily target dosages of 200-1,000 mg/day were evaluated as add-on therapy in adults with refractory partial seizures with or without becoming secondarily generalized. Net reductions in median monthly seizure frequency (active drug minus placebo) with the most efficacious dosages of TPM were 35% in the low-dose trial and 40% in the high-dose trial. Substantial reductions in secondarily generalized seizures were also observed with TPM. TPM appears to be an efficacious new antiepileptic drug in the management of partial epilepsy.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Placebos; Topiramate; Treatment Outcome; United States

In three randomized, double-blind, placebo-controlled add-on European trials, target daily topiramate (TPM) dosages of 400, 600, and 800 mg/day (200, 300, and 400 mg bid) were evaluated in adults with refractory partial seizures with or without becoming secondarily generalized. Median reductions from baseline in monthly seizure rate were 41% with TPM 400 mg/day vs. 1% with placebo (n = 0.065), 46% with TPM 600 mg/day compared to -12% (a 12% increase) with placebo (p < or = 0.005), and 36% with TPM 800 mg/day versus -18% (an 18% increase) with placebo (p < 0.001). Differences between TPM and placebo with respect to percent responders (percent of patients demonstrating a 50% or greater reduction in seizures) significantly favored TPM (p < 0.05) at all three target dosages. Significant reductions in secondarily generalized tonic-clonic seizures compared to placebo were also observed with 400 mg/day (p = 0.002) and 800 mg/day (p < 0.05) of TPM. TPM appears to be a promising new antiepileptic drug for use as adjunctive therapy in adults with refractory partial epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Epilepsies, Partial; Europe; Fructose; Humans; Middle Aged; Placebos; Topiramate; Treatment Outcome

A pooled analysis of data from five similarly designed double-blind, placebo-controlled trials of topiramate (TPM) as add-on therapy in patients with partial epilepsy was performed. The pooled analysis allowed evaluation of efficacy end points and response to treatment for a number of study subgroups not statistically evaluable in the individual study analyses due to limited sample sizes. The five trials included 534 patients, 360 who received TPM at target dosages of 200-1,000 mg daily and 174 who received placebo. In the intent-to-treat pooled analysis, TPM was significantly (p < or = 0.01) superior to placebo in reducing total seizures by > or = 75% or by 100%. When seizure types were evaluated independently, TPM significantly (p < or = 0.001) reduced the frequency of simple partial, complex partial, and secondarily generalized seizures. TPM was significantly (p < 0.001) better than placebo regardless of gender, patient age, baseline seizure rate, and concomitant AEDs. The efficacy of TPM in partial epilepsy is consistent across efficacy end points and across strata defined by study population characteristics.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Multicenter Studies as Topic; Placebos; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Attention; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fatigue; Female; Fructose; Headache; Humans; Male; Medical Records; Middle Aged; Paresthesia; Placebos; Topiramate; Treatment Outcome; Weight Loss

We conducted a multicenter, double-blind, randomized, parallel, placebo-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunctive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41% for topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. There was a 50% or greater reduction from baseline in seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day, 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 100% in seizure frequency, whereas 20% of the topiramate patients were improved to this degree. All intent-to-treat drug-placebo comparisons including seizure reduction, percent responders, and investigator and patient global evaluations significantly (p < or = 0.02) favored topiramate. Treatment-emergent adverse events consisted mainly of neurologic symptoms commonly observed during antiepileptic drug (AED) therapy. Sixteen percent of patients on topiramate discontinued therapy due to adverse events. Results of this study indicate that topiramate is a highly efficacious and generally well tolerated new AED. When large groups of patients are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher doses may prove beneficial to individual patients who tolerate them.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carboplatin; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Headache; Humans; Male; Middle Aged; Nervous System Diseases; Phenytoin; Safety; Topiramate; Treatment Outcome

We conducted a randomized double-blind comparison of three doses of the novel antiepileptic drug (AED) topiramate (200, 400, and 600 mg/day) and placebo as adjunctive therapy in patients with refractory partial onset epilepsy receiving one or two other AEDs at therapeutic concentrations. A total of 181 patients completed the 12-week baseline phase and were randomized to double-blind therapy. Median percent reductions from baseline in average monthly seizure rate, the principal efficacy evaluation, were 13% for placebo, 30% for topiramate 200 mg/day, 48% for topiramate 400 mg/day, and 45% for topiramate 600 mg/day. For the seizure rate comparison of active drug to placebo p values were: topiramate 200 mg/day, p = 0.051; topiramate 400 mg/day, p = 0.007; topiramate 600 mg/day, p < 0.001. Percent responders ( > or = 50% reduction in seizure rates) were 18% for placebo, 27% for topiramate 200 mg/day, 47% for topiramate 400 mg/day (p = 0.013), and 46% for topiramate 600 mg/day (p = 0.027). A significant (p = 0.003) reduction in secondarily generalized seizures compared with placebo treatment was also documented with topiramate. Topiramate plasma concentrations were closely related to dosage, and there were no significant interactions between topiramate and other AEDs. The minimal effective dose of topiramate in this study population was approximately 200 mg/day. Mild or moderate CNS symptoms were the primary treatment-emergent adverse events, but treatment-limiting adverse events occurred in only 9% of patients given topiramate compared with 7% given placebo. Results of this initial well-controlled study in patients indicate that topiramate is a very promising new AED.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsies, Partial; Female; Fructose; Headache; Humans; Male; Middle Aged; Nervous System Diseases; Safety; Topiramate; Treatment Outcome

We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study.. Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks.. TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with > or = 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity.. The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Anticonvulsants; Dizziness; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Fatigue; Female; Fructose; Headache; Humans; Male; Middle Aged; Placebos; Topiramate; Treatment Outcome

We studied the steady-state pharmacokinetic profile of topiramate (TPM) as a function of dose and the effects of comedication with carbamazepine (CBZ).. We enrolled 12 patients with partial epilepsy receiving chronic stable doses of CBZ 300-800 mg every 8 h. In a 6-week period, TPM was added and doses were increased at approximately 2-week intervals from 100 to 200 to 400 mg every 12 h and stabilized at the highest tolerated dose to as high as 400 mg every 12 h. CBZ was tapered in the next 4 weeks when possible, and TPM was maintained as monotherapy at the highest stabilized dose for 2 more weeks. Plasma and urine samples were collected before TPM dosing, after each TPM dose increase, and during TPM monotherapy.. Dose-normalized results (n = 10) for TPM area under the curve from 0 to 12 h (AUC(0-12)), Cmin(0), and Cavg indicated that TPM exhibits linear plasma pharmacokinetics over the dose range of 100- to 400-mg every 12 h when administered with CBZ. Mean TPM AUC(0-12), Cmax, Cmin(0), and Cavg values were approximately 40% lower during CBZ treatment as compared with those during TPM monotherapy (n = 3). TPM oral and nonrenal clearance rates were approximately two- to threefold higher, whereas TPM renal clearance was unchanged during concomitant CBZ treatment (n = 3). There were no significant changes in total and unbound CBZ and CBZ-epoxide (CBZ-E) pharmacokinetics during TPM administration (n = 10). TPM pharmacokinetics during concomitant CBZ treatment were significantly different from those during TPM monotherapy, suggesting that metabolic clearance of TPM increases when CBZ is coadministered.. When CBZ is reduced or discontinued, TPM doses may need to be lowered to maintain equivalent plasma concentrations. Adjusting the CBZ dose for pharmacokinetic reasons when TPM is administered as adjunctive treatment does not appear to be necessary.

Topics: Adult; Anticonvulsants; Biological Availability; Carbamazepine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Metabolic Clearance Rate; Topiramate; Treatment Outcome

The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs. 1%; P = 0.065). Nevertheless, other efficacy variables evidenced statistically significant differences in favor of topiramate: a greater number of treatment responders (> or = 50% reduction in seizures; 35% vs. 8%; P = 0.033); better investigator (P = 0.002) and patient (P = 0.021) global assessments; and greater reductions in secondarily generalized seizures compared to placebo (P = 0.002). The most commonly reported topiramate treatment-emergent adverse events were somnolence, fatigue, abnormal vision, weight decrease, and anxiety. Most adverse events were mild or moderate in severity. Among 7 withdrawals due to limiting adverse events, 6 were CNS-related (in 5 topiramate-treated patients). Results of this trial strongly suggest that topiramate 400 mg/day is effective and well tolerated in the treatment of refractory partial epilepsy.

Topics: Adolescent; Adult; Analysis of Variance; Anticonvulsants; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Europe; Female; Fructose; Humans; Male; Middle Aged; Placebos; Topiramate

The effects of topiramate in 15 patients with drug refractory epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14-21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400-800 mg/day), and nine have discontinued treatment because of adverse events (n = 6), inefficacy (n = 2) or poor compliance (n = 1). Nine patients (69%) continued to have > or = 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for long-term management of refractory epilepsy.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Prospective Studies; Topiramate

Topics: Administration, Intravenous; Anticonvulsants; Child, Preschool; Contrast Media; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Gadolinium; Hamartoma; Humans; Hypothalamic Diseases; Laughter; Levetiracetam; Magnetic Resonance Imaging; Male; Topiramate; Treatment Outcome

Outcome reporting bias occurs when outcomes in research studies are selectively reported, the selection being influenced by the study results. For benefit outcomes, we have shown how risk assessments using the Outcome Reporting Bias in Trials risk classification scale can be used to calculate bias-adjusted treatment effect estimates. This paper presents a new and simpler version of the benefits method, and shows how it can be extended to cover the partial reporting and non-reporting of harm outcomes. Our motivating example is a Cochrane systematic review of 12 studies of Topiramate add-on therapy for drug-resistant partial epilepsy. Bias adjustments for partially reported or unreported outcomes suggest that the review has overestimated the benefits and underestimated the harms of the test treatment.

Topics: Algorithms; Anticonvulsants; Bias; Drug Resistant Epilepsy; Epilepsies, Partial; Humans; Meta-Analysis as Topic; Models, Statistical; Outcome Assessment, Health Care; Research Design; Systematic Reviews as Topic; Topiramate

Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.. To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.. A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.. Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.. Antiepileptic drug treatment pattern according to seizure type and comorbidities.. Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).. Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety Disorders; Comorbidity; Dissociative Disorders; Epilepsies, Partial; Epilepsy, Generalized; Female; Headache Disorders; Humans; Lamotrigine; Levetiracetam; Mental Disorders; Migraine Disorders; Mood Disorders; Oxcarbazepine; Phenytoin; Retrospective Studies; Risk; Teratogens; Topiramate; Valproic Acid; Young Adult

Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP.. The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures.. Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP.. Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Lamotrigine; Male; Middle Aged; Psychoses, Substance-Induced; Retrospective Studies; Risk Factors; Topiramate

To investigate the effects of topiramate (TPM), zonisamide (ZNS), and levetiracetam (LEV) on cognitive network activations in patients with focal epilepsy using an fMRI language task.. In a retrospective, cross-sectional study, we identified patients from our clinical database of verbal fluency fMRI studies who were treated with either TPM (n = 32) or ZNS (n = 51). We matched 62 patients for clinical measures who took LEV but not TPM or ZNS. We entered antiepileptic comedications as nuisance variables and compared out-of-scanner psychometric measures for verbal fluency and working memory between groups.. Out-of-scanner psychometric data showed overall poorer performance for TPM compared to ZNS and LEV and poorer working memory performance in ZNS-treated patients compared to LEV-treated patients. We found common fMRI effects in patients taking ZNS and TPM, with decreased activations in cognitive frontal and parietal lobe networks compared to those taking LEV. Impaired deactivation was seen only with TPM.. Our findings suggest that TPM and ZNS are associated with similar dysfunctions of frontal and parietal cognitive networks, which are associated with impaired performance. TPM is also associated with impaired attenuation of language-associated deactivation. These studies imply medication-specific effects on the functional neuroanatomy of language and working memory networks.. This study provides Class III evidence that in patients with focal epilepsy, TPM and ZNS compared to LEV lead to disruption of language and working memory networks.

Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Sectional Studies; Epilepsies, Partial; Female; Fructose; Functional Laterality; Humans; Image Processing, Computer-Assisted; Isoxazoles; Language; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Oxygen; Retrospective Studies; Topiramate; Zonisamide

Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated.. We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, >6weeks after, and >6months after. An untreated control group (n=14) underwent similar measurement. We combined these data with those of our previous investigation (n=34 patients and 16 controls) of a very similar design.. There were no differences in outcome measures between the two inducing AEDs nor among the three noninducing AEDs. Total cholesterol (TC), atherogenic lipids, and CRP were higher under inducer treatment than in controls. All measures were elevated under inducer treatment relative to noninducer treatment, including TC (24mg/dL higher, 95% CI: 17.5-29.9, p<0.001) and CRP (72% higher, 95% CI: 41%-111%, p<0.001). The difference between drug treatments was clinically meaningful for atherogenic lipids (16%, 95% CI: 11%-20%, p<0.001) but small for high-density lipoprotein cholesterol (5%, 95% CI: 1%-9%, p<0.05). All measures were stable between 6weeks and 6months after drug switch.. We demonstrate that switching from inducing to noninducing AEDs produces an enduring reduction in serum lipids and CRP. These results provide further evidence that inducing AEDs may be associated with elevated vascular disease risk. These are the first vascular risk marker data in patients taking zonisamide, which shows a profile similar to that of other noninducing AEDs.

Topics: Anticonvulsants; Biomarkers; C-Reactive Protein; Carbamazepine; Drug Substitution; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Lipids; Male; Middle Aged; Phenytoin; Piracetam; Time Factors; Topiramate; Treatment Outcome; Triazines; Zonisamide

This work aimed to evaluate the metabolic and atherogenic effects of long-term antiepileptic drugs in a group of Egyptian epileptic patients. Sixty-nine epileptic patients on antiepileptic drug monotherapy for at least 2 years and 34 control subjects were recruited in this study. Patients were divided into 5 subgroups according to antiepileptic drugs used (valproate, carbamazepine, lamotrigine, topiramate, and levetiracetam). Fasting lipid profile (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), lipoprotein(a), homocysteine, free thyroxine, thyroid-stimulating hormone, and common carotid artery intima-media thickness were measured for all subjects. Significant higher mean values of low-density lipoprotein cholesterol, low-density lipoprotein / high-density lipoprotein ratio, lipoprotein(a), homocysteine, significantly lower mean value of high-density lipoprotein cholesterol, and significantly larger diameter of common carotid artery intima-media thickness were observed in each drug-treated group versus control group. Our study supports that long-term monotherapy treatment with valproate, carbamazepine, lamotrigine, and topiramate had altered markers of vascular risk that might enhance atherosclerosis, whereas levetiracetam exerted minimal effect.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Carotid Arteries; Carotid Intima-Media Thickness; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Intracranial Arteriosclerosis; Lamotrigine; Levetiracetam; Male; Piracetam; Topiramate; Triazines; Valproic Acid

To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice.. Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.. This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).. LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Epilepsies, Partial; Female; Fructose; Humans; Lamotrigine; Male; Middle Aged; Oxcarbazepine; Prospective Studies; Seizures; Topiramate; Treatment Failure; Triazines; Valproic Acid; Young Adult

It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.. This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.. A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%).. This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; China; Epilepsies, Partial; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

To investigate the relationships between demographic data, seizure-related factors, anti-epileptic drugs (AEDs) taking, and depressive symptoms in patients with epilepsy (PWE), determining the major clinical risk factors of depression.. Patients with epilepsy who visited our epilepsy clinic from 2010 to 2012 were included. The clinical data were collected, and Hamilton Depression Rating Scale (HAMD), National Hospital Seizure Severity Scale (NHS3) and Pittsburgh Sleep Quality Index (PSQI) were evaluated.. A total of 116 PWE were recruited. They were divided into three groups. Age, duration of epilepsy, percentages of patients with partial seizures, history of status epilepticus (SE), using topiramate (TPM) or clonazepam (CZP), and using greater than or equal to 2 types of AEDs were all significantly higher in patients with moderate depressive symptoms than patients without depression. HAMD scores were positively correlated with age, duration of epilepsy, and the number of AEDs taking, respectively. PSQI scores were positively correlated with HAMD scores in patients with depressive symptoms. Age greater than 35 years, females, having partial seizures, history of SE, and using TPM were independent predictors of depressive symptoms in PWE by regression analysis.. Age greater than 35 years, females, having partial seizures, history of SE, and using TPM might become risk factors for depressive symptoms in PWE.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Depression; Epilepsies, Partial; Epilepsy; Female; Fructose; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sex Factors; Status Epilepticus; Time Factors; Topiramate; Young Adult

Antiepileptic drugs have been reported to reduce the levels of serum immunoglobulins and affect the production and levels of certain cytokines. We investigated the effects of valproic acid (VPA) and topiramate (TPM) on the blood levels of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and TNF-α in children with idiopathic generalized and partial epilepsy.. Forty prepubertal children aged 6-12 (mean 8.3±1.7) years, 19/40 (47.5%) female and 21/40 (52.5%) male, with idiopathic generalized or partial epilepsy diagnosed in the child neurology outpatient clinic were included. The patients were divided into two treatment groups: 20 were treated with VPA and 20 with TPM. The plasma levels of IL-1α, IL-1β, IL-6, IL-10, TNF-α were measured using ELISA method before the initiation of treatment and at the 6th and 12th months of the treatment. The Chi-square test was used to compare qualitative data. To compare the periods, recurrence measurements were done using variance analysis and Freidman 2-sided variance analysis. p<0.05 was considered as statistically significant.. In the VPA group, the levels of IL-1α significantly increased at 12 months while the levels of IL-10 decreased at 6 months of treatment compared to values before treatment (p<0.05). There was no significant difference in levels of IL-1β, IL-6, TNF-α (p>0.05). In the TPM group, lower levels of IL-10 were observed at 6th and 12th months compared to the onset of treatment (p<0.05).. The results of this study demonstrated that VPA and TPM might lead to changes in the levels of cytokines in epileptic patients. The next step would be to investigate the relation of these findings to the outcome of epilepsy and response to treatment.

Topics: Anticonvulsants; Chi-Square Distribution; Child; Cytokines; Disease Progression; Electroencephalography; Enzyme-Linked Immunosorbent Assay; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Magnetic Resonance Imaging; Male; Topiramate; Valproic Acid

The aim of this observational study was to obtain information regarding efficacy and safety of add-on levetiracetam (LEV; n=32) in Japanese patients with refractory partial seizures in an everyday clinical setting, relative to control AEDs (n=30). This is the first study of LEV add-on therapy conducted in Japan since approval was made. The medical charts of patients were retrospectively reviewed. The efficacy variables were seizure freedom and ≥50% reduction in seizure frequency. A significantly higher response to LEV was demonstrated in patients with all seizure types at baseline, relative to control AEDs. In patients with a duration of epilepsy of at least 10 years, significant effects in response to LEV were demonstrated with regards to efficacy variables, relative to control AEDs, thus providing meaningful results. Only two patients (6.2%) discontinued LEV treatment due to worsening of seizures, but no discontinuation was reported due to adverse events. LEV as add-on therapy to other AEDs is a promising useful treatment option for patients with refractory partial seizures without notable effects on safety, indicating that this treatment regimen might be recommended for such patients.

Topics: Adult; Anticonvulsants; Benzodiazepines; Clobazam; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Female; Fructose; Humans; Japan; Lamotrigine; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy.. This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis.. Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a treatment retention rate of 100%. The effectiveness of AED in terms of reduction of seizure frequency was highest for PHT (100%) and PHB (98%) followed by CBZ (96%) and VPA (95%). PHB and PHT were the cheapest of all AEDs (42 I$ and 56 I$/ year respectively). The costs of VPA and CBZ were two times and LTG and TOP were six to eight times higher. Adverse drug reaction (ADR) were observed among 140 (24.5%) of those with monotherapy. PHT (64%) was the most common drug to cause ADR, CBZ was at the bottom of the list to cause adverse effect (11.6%). VPA and PHB caused weight gain commonly. Adjustment of drug dose or withdrawal due to ADRs was necessary in 39% with PHT and 26% with PHB.. Though PHT and PHB are cheapest and efficacious among all, CBZ and VPA are less costly, effective and well tolerated drug for seizure control in context of Bangladesh.

Topics: Adolescent; Adult; Anticonvulsants; Bangladesh; Carbamazepine; Child; Drug Combinations; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Fructose; Hospitals, Teaching; Humans; Male; Middle Aged; Phenobarbital; Phenytoin; Prohibitins; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Valproic Acid

Topiramate (TPM) is known to cause language impairment in healthy volunteers and patients with epilepsy. We assessed the effects of TPM on functional language networks in both patients with focal epilepsies and healthy controls using functional magnetic resonance imaging (fMRI).. We obtained fMRI data in 24 controls and 35 patients with frontal lobe epilepsy using a simple verbal fluency (VF) paradigm. Eight of the 35 patients were treated with TPM in polytherapy. We compared cognitive task related activations and de-activations in patients taking TPM with patients taking other AEDs and healthy controls. In a longitudinal pilot study with VF-fMRI paradigm, we studied two patients with focal epilepsies twice, prior to starting and on stable doses of TPM, two patients twice, before and after tapering TPM completely and two healthy controls twice, before and after single doses of 200mg TPM.. Cross sectional analyses of VF-fMRI showed a reduction in the task-related deactivation of the default mode network (DMN) in patients taking TPM. The longitudinal study corroborated these findings as both chronic administration and a single dose of TPM were associated with impaired categorical verbal fluency and disruption of task-related deactivations.. Similar neuropsychological and fMRI findings in patients and healthy controls indicate a specific effect of TPM in default mode network areas that may be essential components of the language network. Our preliminary data suggest a mechanism by which TPM impairs cognitive processing during language function and highlights the sensitivity of fMRI to detect the effects of AEDs on cognitive brain networks.

Topics: Adult; Anticonvulsants; Cognition; Cross-Sectional Studies; Epilepsies, Partial; Female; Fructose; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Topiramate; Treatment Outcome; Young Adult

Topics: Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Oxcarbazepine; Topiramate; Triazines

Carbamazepine (CBZ) and topiramate (TPM) are among commonly used antiepileptic drugs. The acute actions of these drugs are well known but the effects of long-term use on partially induced epileptiform characteristics are yet to be clarified. The rats were received CBZ (154 mg/kg/day), TPM (10 mg/kg/day) or tap water by gavage. We investigated penicillin-induced cortical epileptiform activity and electroencephalogram spectral power of rats by using electrocorticogram recordings. Animals were anesthetized with i.p. urethane (1·25 g/kg). Analysis of electroencephalogram recordings prior to epileptiform activity revealed that 3-week treatment of CBZ significantly increased relative power of delta (P<0·01) while reduced alpha (P<0·017) and beta (P<0·017) relative power compared to both control group and TPM group. TPM had no effect on absolute power and relative power of any frequency band. TPM treatment of 21 days significantly reduced the spike frequency (P<0·01). This preventive effect was missing in CBZ-treated rats. Upon the application of the last dose of drugs during ongoing epileptiform activity, the drugs suppressed the epileptiform activity. However, TPM was more rapid and effective than CBZ. In conclusion, our in vivo electrophysiological data suggest that TPM is more effective in animal model of partial epilepsy at the applied doses in this study.

Topics: Animals; Anticonvulsants; Brain; Carbamazepine; Disease Models, Animal; Electroencephalography; Epilepsies, Partial; Female; Fructose; Rats; Rats, Sprague-Dawley; Topiramate

Recently, new anti-epileptic drugs (AEDs) have been more frequently selected to treat epilepsy. In the present study, we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.. Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine (OXC), lamotrigine (LTG) or topiramate (TPM) therapy. Each group included monotherapy and add-on therapy subgroups. We followed all patients for one year and recorded the indexes of efficacy and safety in detail.. A total of 909 patients finished the follow-up observation. No significant difference was found in proportion of patients with > or = 50% reduction, > or = 75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months. In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with > or = 50% reduction (P = 0.002), > or = 75% reduction (P < 0.0001) and 100% seizure reduction (P = 0.009) in the monotherapy subgroup, and about > or = 75% reduction and 100% seizure reduction in the add-on therapy subgroup (P < 0.0001). The efficacy between the add-on and monotherapy subgroups showed a statistical difference. The safety of the three newer AEDs was good.. The three newer AEDs all showed good efficacy and tolerability for partial epilepsy. And the efficacy can be maintained for at least one year.

Topics: Anticonvulsants; Carbamazepine; China; Epilepsies, Partial; Follow-Up Studies; Fructose; Humans; Lamotrigine; Oxcarbazepine; Topiramate; Treatment Outcome; Triazines

Topics: Acidosis; Acidosis, Renal Tubular; Aged; Anticonvulsants; Cerebral Hemorrhage, Traumatic; Comorbidity; Drug Substitution; Epilepsies, Partial; Fructose; Humans; Male; Phenytoin; Polypharmacy; Schizophrenia, Paranoid; Topiramate

Seventy-two elderly patients with a possible diagnosis of epilepsy were studied. A study included the evaluation of anamnesis, clinical and neurological examination, EEG and/or video-EEG-monitoring, MRI of the brain. The follow-up period was 1-5 years (on average 3 years). Epilepsy was confirmed in 58 cases. Symptomatic partial epilepsy was diagnosed in 43,1% patients, cryptogenic - in 55,2%. Cerebrovascular accidents were the most frequent cause of symptomatic epilepsy. The distinct feature of the cohort studied was the non-compliance recorded in a half of all patients. In the end of the study, 46,6% patients received carbamazepine, 34,5% - valproate, 24,1% - phenobarbital, 13,8% - topiramate, 3,4% - phenytoin, 1,7% - lamotrigine and 12,1% of patients did not use antiepileptic drugs. Clinical features, efficacy of diagnosis and treatment as well as reasons of non-compliance in elderly epileptic patients were described and analyzed.

Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Carbamazepine; Electroencephalography; Epilepsies, Partial; Epilepsy; Female; Fructose; Humans; Lamotrigine; Magnetic Resonance Imaging; Male; Middle Aged; Patient Compliance; Phenobarbital; Phenytoin; Topiramate; Triazines; Valproic Acid

Topiramate is one of the most commonly prescribed newer antiepileptic drugs. However, we have encountered quite a few cases of pediatric epileptic patients on topiramate complaining about the symptoms related to hypohidrosis. The aim of this study was to determine the incidence and define the clinical characteristics of hypohidrosis-related symptoms with topiramate in pediatric patients.. Data was collected prospectively on 264 patients diagnosed as having epilepsy and treated with topiramate at the Department of Pediatrics, Chonbuk National University Hospital between July 2004 and July 2006. The data were collected by direct interview after at least 3 months had elapsed from the initiation of the medication.. The study group was composed of 70 boys and 81 girls, with a mean age of 33.1 +/- 43.2 months. The mean duration of topiramate treatment was 13.4 +/- 15.0 months; 52 patients (34.4%) were treated with topiramate only and 99 patients (65.6%) were on polytherapy including topiramate; 59 out of 151 patients (39.1%) experienced hypohidrosis-related symptoms: such as facial flushing, lethargy, itching sensation, irritability with hyperthermia, heat sensation or heat intolerance. However, there were no patients complaining of hypohidrosis-related symptoms among those who were taking antiepileptic drugs other than topiramate.. Our results suggest that topiramate induces hypohidrosis-related symptoms more often than we expected, especially in pediatric patients. We recommend that pediatric epileptic patients taking topiramate should be warned to avoid hot and humid environments, especially during the hot summer season.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cross-Sectional Studies; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Hypohidrosis; Infant; Male; Prospective Studies; Topiramate

For a retrospective observational investigation based on real clinical practice of relative efficacy of valpoic acid (VPA), carbamazepine (CBZ) and topiramate (TPM) we have selected 106 patients with age of seizure onset before 17 years with a undoubted diagnosis of symptomatic or cryptogenic occipital lobe epilepsy (OLE), who had received treatment according to ILAE recommendations, and observation time since the last treatment change was from 2 to 10 years. Patients suspicious for idiopathic epilepsies were excluded. The groups of patient receiving CBZ, VPA and TPM did not differ significantly in presenting unfavorable prognostic factors and dose regimes that allowed to conduct direct comparison of efficacy of the investigated drugs. Efficacy of VPA in children with OLE was higher compared with CBZ (69% vs 36%, p < 0.01) and TPM (69% vs 8%, p < 0.001). CBZ and TPM caused seizure aggravation more frequently than VPA (12% and 13% respectively vs 1%, p < 0.001). In case of presence of clinico-electroencephalografic and MRI signs of significant organic brain damage and in patients with seizure onset under 11 years TPM was not effective. In case of focal cortical dysphasia the efficacy of CBZ was lower than VPA (20% vs 63%, p < 0.05). In MRI-negative cases VPA was most effective (79% vs 44% for CBZ, p < 0.001 and 29% for TPM, p < 0.01). Efficacy of CBZ and TPM reduces proportionally the number of previously used antiepileptic drugs (AEDs), this tendency is noted also for VPA but as a second AED it was more effective than CBZ and TPM (56% vs 15%, p < 0.01 and 14%, p < 0.05, respectively); as a first AED VPA was also most effective (82% vs 37%, p < 0.001 for CBZ and 82% vs 33%, p < 0.01 for TPM). Adverse effects were more frequent during treatment with CBZ and TPM, than VPA (21% vs 6%, p < 0.001 and 17% vs 6%, p < 0.05).

Topics: Anticonvulsants; Carbamazepine; Child; Epilepsies, Partial; Female; Fructose; Humans; Male; Retrospective Studies; Topiramate; Treatment Outcome; Valproic Acid

Acute encephalitis with refractory repetitive partial seizure (AERRPS) is a peculiar type of post-encephalitic/encephalopathic epilepsy. Here we report an analysis of AERRPS in a series of children and propose an effective treatment option for seizure control in these children.. We retrospectively reviewed cases of AERRPS treated in a pediatric intensive care unit, between February 2002 and June 2006. Clinical characteristics were systemically assessed. Burst suppression coma was induced by high-dose suppressive therapy; 24-h electroencephalogram (EEG) monitoring was performed on each patient. The goal of treatment was to achieve complete clinical seizure control or burst-suppression pattern on EEG, aiming for an interburst interval of >5s. Brain imaging was done for each patient.. There were nine patients (seven boys), aged 5-15 years. Clinical symptoms included fever (100%), upper respiratory symptoms (66.7%) and altered consciousness (66.7%). All patients received multiple high-dose suppressive drugs and were intubated with/without inotropic agents. Seizures in three patients were stopped after high-dose lidocaine infusion (6-8 mg/kg/h) in the acute stage and three patients were stopped after high dose phenobarbital (serum level 60-80 ug/mL) combined with high-dose oral topiramate (15-20 mg/kg/day). Follow-up for this study was 16-61 months. Two subjects died while seven developed epilepsy and/or neurologic deficits; none returned to baseline. All survivors were discharged and continued multiple antiepileptic medications.. Our data indicates that children with AERRPS have high mortality and morbidity rates. High-dose topiramate combined with high-dose lidocaine infusion or high-dose phenobarbital in the acute stage might be an effective treatment option for children with AERRPS.

Topics: Acute Disease; Adolescent; Anticonvulsants; Child; Drug Therapy, Combination; Electroencephalography; Encephalitis; Epilepsies, Partial; Female; Fructose; Humans; Lidocaine; Magnetic Resonance Imaging; Male; Phenobarbital; Radiography; Severity of Illness Index; Syndrome; Topiramate; Treatment Outcome

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

To evaluate the long-term efficacy and tolerability of topiramate (TPM) as add-on therapy in patients with refractory partial epilepsy.. This is a retrospective, single-center, long-term observational study. Patients fulfilling the criteria of medical intractability proposed by Berg et al. were entered into the study if they were newly prescribed TPM as add-on therapy between January 2000 and June 2002. The usual starting dosage of TPM was 50 mg/day and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed every year during 5-year follow-up in the "intention-to-treat (ITT) population." Retention rate was estimated by Kaplan-Meyer analysis.. A total of 125 patients were included in the study and 107 patients (85.6%) were followed for 5 years. Retention rate was 87.2% at 1 year and 64% at 5 years. At the end of 5 years, the median seizure frequency reduction rate was 69.0% and responder rate was 43.2% in the ITT population. Cumulative seizure-free rate (SFR) was 30.4% and the terminal 1-year SFR was 12.8% in the ITT population (20.0% in completers) at 5-year follow-up. Adverse events (AEs) occurred in 39.2% of patients, including significant AEs leading to antiepileptic drug (AED) withdrawal in 14.4%. The most common AEs were anorexia (16.0%), weight loss (10.4%), and gastrointestinal symptoms (8.8%). Concomitant AEDs were reduced in 25.0% of the completers.. Low-dose and slow-dose escalation of TPM in add-on therapy for patients with refractory partial epilepsy is effective and well tolerated in long-term, individualized clinical practice.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Maximum Tolerated Dose; Middle Aged; Observation; Outcome Assessment, Health Care; Retrospective Studies; Secondary Prevention; Topiramate; Young Adult

We report the case of a patient with complex partial seizures who developed a nonfluent aphasia when topiramate was added to his therapy. This emergent adverse effect appeared to be reversible, as language performance improved after discontinuation of topiramate. Interictal SPECT performed when the patient was aphasic revealed a focal perfusion reduction in the left lateral and mesial frontal cortex, which was no longer evident at a follow-up study after language recovery.

Topics: Anticonvulsants; Aphasia, Broca; Brain Mapping; Cerebrovascular Circulation; Epilepsies, Partial; Frontal Lobe; Fructose; Functional Laterality; Humans; Tomography, Emission-Computed, Single-Photon; Topiramate

Topics: Anticonvulsants; Child; Epilepsies, Partial; Fructose; Humans; Hypohidrosis; Male; Topiramate

The substantia nigra pars reticulata (SNR) is known to play a role in gating and control of seizures. Prompted by the observation that intrahippocampal topiramate (TPM) administration does not suppress limbic seizures in the focal pilocarpine model, we investigated the role of the SNR in the anticonvulsant mechanism of action of TPM.. Limbic seizures were evoked in freely moving rats by intrahippocampal administration of pilocarpine via a microdialysis probe. Changes in hippocampal extracellular (EC) glutamate and GABA concentrations were monitored. Effects of intraperitoneal (10-200 mg/kg), intrahippocampal (1-5 mM), and bilateral intranigral (100-300 nmol) TPM administration on pilocarpine-induced seizures and neurochemical changes were evaluated. Effects of TPM administration alone on hippocampal and nigral EC amino acid concentrations were also studied.. Systemic and intranigral, but not intrahippocampal TPM administration suppressed pilocarpine-induced seizures and neurochemical changes. Nigral GABA(A) receptor blockade by picrotoxin abolished the anticonvulsant effect of TPM in SNR. Systemic TPM administration increased hippocampal glutamate and decreased GABA. Intranigral TPM administration increased hippocampal glutamate, but not GABA. Intrahippocampal TPM increased hippocampal glutamate and GABA, but only at high concentrations.. In the focal pilocarpine model, TPM does not exert its anticonvulsant effect at the site of seizure initiation. We identified the SNR as a site of action of TPM, and showed that the nigral GABA-ergic system is central to TPM's anticonvulsant effect in SNR. Anticonvulsant effects and neurochemical changes in hippocampus following intranigral TPM administration suggest the existence of a nigro-hippocampal circuit, which may be involved in the control of limbic seizures.

Topics: Animals; Anticonvulsants; Area Under Curve; Behavior, Animal; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsies, Partial; Fructose; Functional Laterality; gamma-Aminobutyric Acid; Glutamates; Hippocampus; Male; Microdialysis; Microinjections; Pilocarpine; Rats; Rats, Wistar; Seizures; Substantia Nigra; Synaptic Transmission; Topiramate

Congenital bilateral perisylvian syndrome (CBPS) is a rare neurological disorder characterised by pseudobulbar palsy, cognitive deficits and epilepsy associated with bilateral perisylvian cortical dysplasia on neuroimaging studies. We report a long-term follow-up of a 18-years girl diagnosed with CBPS according to the typical clinical and magnetic resonance imaging (MRI) features. The patient showed faciopharyngoglossomasticatory diplegia, severe dysarthria, ataxia, spastic quadriparesis and severe mental retardation. Brain MRI evidenced bilateral perisylvian cortical dysplasia. Since early life she suffered from complex febrile seizures and epilepsy consisting of complex partial attacks with affective manifestations associated with centro-temporal EEG abnormalities. During 18 years of follow-up she was treated with phenobarbital, carbamazepine, lamotrigine, gabapentin but did not show any significant clinical improvement. Subsequently, monotherapy with phenytoin (PHT) was followed by a significant clinical improvement. At age 17, because of adverse effects, PHT was gradually substituted by topiramate (TPM). Full control of seizures was obtained at the age of 17 years with TPM. EEG abnormalities throughout the years have been reduced according to the clinical course. These findings emphasised the importance of long-term follow-up, suggesting that the prognosis for epilepsy may not be predicted based on the early response to treatment or on the presence of structural encephalic abnormalities, as reported in the literature.

Topics: Adolescent; Cerebral Cortex; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Fructose; Globus Pallidus; Humans; Intellectual Disability; Magnetic Resonance Imaging; Nervous System Malformations; Phenytoin; Pseudobulbar Palsy; Quadriplegia; Syndrome; Topiramate; Treatment Outcome

Topics: Adult; Anticonvulsants; Antidepressive Agents, Second-Generation; Carbamazepine; Citalopram; Dose-Response Relationship, Drug; Epilepsies, Partial; Fructose; Humans; Lamotrigine; Male; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Topiramate; Triazines

To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy.. Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (> or =5% incidence) AEs were calculated for patients completing the 12-week study.. The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits.. This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Anxiety; Carbamazepine; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Feeding and Eating Disorders; Female; Fructose; Headache; Humans; Incidence; Male; Meta-Analysis as Topic; Middle Aged; Paresthesia; Placebos; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Time Factors; Topiramate; Weight Loss

The objective of our study was to investigate the effect of topiramate (TPM) on the Lyapunov exponent of EEG by means of quantitative pharmacoelectroencephalography (QPEEG) and nonlinear analysis methods. One dose of TPM was administrated to epileptics and healthy adults. EEG samples were obtained prior to and at regular intervals (at 0.5, 1, 2, 4, 6, 8, 12, 24 hours) within the 24 hours following the administration of TPM. EEG activity was processed with nonlinear analysis methods. The Lyapunov exponent of the scalp areas was calculated through 60 s epochs without artifacts after each recording. The statistical difference between baseline predrug assessment and each postdrug control was calculated by computing the paired t test. Results showed that the Lyapunov exponent increased first, then decreased, then increased finally. We conclude that TPM can change the complexity of EEG.

Topics: Adult; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Male; Topiramate

Childhood epilepsy remains a challenge to treat. Despite the availability of antiepileptic drugs (AEDs), >25% of children with childhood epilepsy continue to have seizures. Conventional AEDs have been the mainstay of therapy for many years but are often poorly tolerated and have a tendency to interact with other drugs. Current American Academy of Neurology guidelines support the use of four of the newer AEDs (gabapentin, lamotrigine, topiramate, and oxcarbazepine) as adjunctive treatment of refractory partial seizures in children, based on class I evidence. This paper includes a summary of the results from a recent randomized, double-blind, placebo-controlled study, which shows that levetiracetam is also effective and well tolerated in this pediatric population, and provides evidence supporting its use in refractory partial seizures in children.

Topics: Amines; Anticonvulsants; Carbamazepine; Child; Cross-Sectional Studies; Cyclohexanecarboxylic Acids; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Oxcarbazepine; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Triazines; United States

The incidence of renal stone disease in patients receiving topiramate (Topamax) is 2-4 times that expected in the background population. This has been attributed to a weak carbonic anhydrase inhibitor effect, but published data are scant. Following three cases of renal stones in patients receiving topiramate, we evaluated biochemical risk for nephrolithiasis in eight further unselected patients. Most patients demonstrated inadequate urinary acidification and hypocitraturia; in some cases citrate was undetectable. Several patients also had other risk factors for nephrolithiasis, including increased urinary sodium, calcium and oxalate excretion. The biochemical changes induced by topiramate appear highly penetrant. Experience with this drug is relatively short-lived and it is being prescribed for long-term use in (often) relatively young patients. This report highlights the significantly increased metabolic risk of stone formation in patients receiving topiramate.

Topics: Adult; Calcium; Citric Acid; Epilepsies, Partial; Female; Fructose; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Male; Middle Aged; Neuroprotective Agents; Oxalates; Risk Factors; Sodium; Topiramate

Many studies showed that Topiramate (TPM) may be a useful drug in a wide spectrum of childhood epilepsies. We report a 3-month-old female with stormy onset of secondarily generalized partial seizures. She showed a high seizure frequency and a progressive worsening electroencephalogram (EEG), despite standard antiepileptic drugs administration. TPM succeeded in controlling seizures, even after the other drugs were discontinued. This case suggests that TPM may represent a good choice for the treatment of partial seizures refractory to conventional drugs in infants.

Topics: Anticonvulsants; Drug Administration Schedule; Drug Resistance; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Infant; Topiramate

Thirty patients diagnosed with partial epilepsy (PE): 17 cases with cryptogenic PE, 11--with symptomatic PE and 2--with symptomatic generalized PE, have been switched to topamax monotherapy, in dosage 50-200 mg daily, for 3 months. A type of seizures--simple partial, complex partial and secondary generalized, was taken into account, when considering topamax efficacy. A complete elimination of seizures was achieved after 3 months treatment in 80% of the cases, the mostly pronounced effect being demonstrated for secondary generalized seizures. A decrease of seizures frequency was shown for all types, but in simple partial and secondary generalized seizures the effect emerged earlier (after 1 month of the treatment) comparing to complex partial seizures. Good tolerability of topamax was observed.

Topics: Adolescent; Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Male; Middle Aged; Topiramate; Treatment Outcome

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Infant; Male; Time Factors; Topiramate; Treatment Outcome

To evaluate the impact of different dosages of topiramate (TPM) add-on to stable antiepileptic therapy for refractory partial epilepsy in adults.. Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 patients treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving placebo.. Seizures were reduced by >/=50% from baseline in 41% of TPM-treated patients and 15% of placebo-treated patients (P < 0.001); 5 and 0.8%, respectively, were seizure-free (P < 0.003). TPM was significantly better than placebo regardless of gender, age, baseline seizure rate as well as number and type of concomitant antiepileptic drugs. Efficacy was statistically significant in favour of TPM at all dose levels: at least 50% seizure reduction was achieved in 40% of patients with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800 mg TPM when compared with 15% with placebo (P

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Retrospective Studies; Topiramate

Hypohidrosis during topiramate (TPM) treatment was recently reported in children. We describe an adult epilepsy patient who developed inability to sweat as well as heat intolerance while undergoing treatment with TPM.. To detect the site of the sweat block, patient underwent examination of sweat gland function, cardiovascular autonomic test, and body temperature rhythm determination.. During TPM treatment, cardiovascular autonomic function and circadian rhythm of body core temperature were normal, whereas thermoregulatory sweat test (TST) showed anhydrosis. This adverse drug effect was quickly resolved after drug discontinuation.. Because of normal cardiovascular autonomic function and central and peripheral thermoregulatory mechanisms, we hypothesize that hypohidrosis during TPM treatment could be due to a carbonic anhydrases (CA) block at the level of sweat gland.

Topics: Adult; Anticonvulsants; Body Temperature Regulation; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsies, Partial; Epilepsy, Complex Partial; Fructose; Heat Exhaustion; Humans; Hypohidrosis; Male; Sweating; Topiramate

Efficacy of topiramate usage in combined therapy of 35 patients (25 adults and 10 children) with therapy resistant epilepsy was analyzed. In 11.4% of the cases, medication remission for a period of up to 3 months has been achieved. Therapeutic efficacy, with reducing the number of fits by half was achieved in 40% of the cases. In children topiramate therapy was less beneficial. The authors emphasize a good tolerability of topiramate, along with a first ever described side-effect, emerging as a spot pigmentation. The results obtained reveal effectiveness of topiramate using in epileptology, in particular, in drug-resistant epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Drug Tolerance; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Pigmentation Disorders; Topiramate; Treatment Outcome

Topics: Acetazolamide; Acute Disease; Adult; Anticonvulsants; Epilepsies, Partial; Female; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Latanoprost; Myopia; Prostaglandins F, Synthetic; Topiramate; Treatment Outcome

The authors report a 51-year-old women with pharmacoresistant partial epilepsy who tolerated well valproate monotherapy and in combination with several other antiepileptic drugs, but developed symptoms and signs of reversible hepatic failure under a combination of valproate and topiramate. Symptoms resolved after discontinuation of VPA. This case provides further anecdotal evidence that topiramate may increase the risk of liver failure when given in combination with other potentially hepatotoxic antiepileptic drugs.

Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Intracranial Aneurysm; Liver Function Tests; Middle Aged; Postoperative Complications; Topiramate; Valproic Acid

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

To assess clinical trials for evidence that antiepileptic drugs (AED) aggravate partial seizures. To determine if the methodology used to examine drug efficacy can also be used to examine seizure aggravation.. It is widely accepted that AED aggravate epilepsy in some patients. However, there is little published objective or quantitative evidence. Most reports concern generalized epilepsies.. Pharmaceutical companies responsible for the development of five of the new AED were asked to provide data concerning seizure increases during randomized placebo-controlled, add-on clinical trials in patients with uncontrolled partial seizures. Seizure frequency in individual patients taking drug or placebo was compared with the baseline pretreatment seizure frequency. The counterpart of the 50% reduction used in efficacy analyses is a 100% increase, because both represent a twofold change. A dose-response relationship was also explored.. More than 40% of subjects in clinical trials of tiagabine (TGB), topiramate (TPM), and levetiracetam (LEV) experienced an increase in seizures while taking a placebo. Seizure increases were no more likely to occur when taking any of the three drugs than taking placebo. A doubling or more of seizure frequency was less likely to occur with TPM or LEV than with placebo but more likely with TGB. However, for TGB, this did not reach significance. There was some evidence for a dose-response effect with TGB but a negative effect with TPM (aggravation less likely with increasing dose). Data on gabapentin and lamotrigine were not provided.. Many patients with partial seizures experience an increase in seizures when a new AED is added to their therapy. However, it occurs no more frequently when taking drug than placebo. It probably represents the spontaneous fluctuation of seizure frequency. When a patient who has started a new AED deteriorates, this is not necessarily a drug effect.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Generalized; Fructose; Humans; Levetiracetam; Nipecotic Acids; Piracetam; Randomized Controlled Trials as Topic; Retrospective Studies; Tiagabine; Topiramate

Localization-related epilepsy, the most common type of seizure disorder, often provides major management problems. Five new antiepileptic drugs (AEDs) with different mechanisms of action have been licensed in the United Kingdom in the 1990s for adjunctive use in the management of poorly controlled partial seizures. These were, in chronologic order, vigabatrin, lamotrigine, gabapentin, topiramate, and tiagabine. Their practical deployment is explored here. Mention also is made of clobazam and acetazolamide. Combination therapy with two or even three AEDs having complementary pharmacologic effects can provide an essential contribution to the management of partial seizures. This article discusses some of the pharmacologic strategies used in treating patients with refractory localization-related epilepsy.

Topics: Acetates; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Nipecotic Acids; Practice Patterns, Physicians'; Tiagabine; Topiramate; Treatment Outcome; Triazines; Vigabatrin

Topiramate (TPM) is a new drug currently used in Brazil. We verified the clinical responses to TPM in children under 15 years-old. We started with 12.5 mg/day (1-7 mg/kg/day) and the doses increased 12,5 mg each week. Eleven children were studied, 9 females and 2 males, from 3 to 14 years-old with partial epilepsy associated to different etiological factors. Only one patient had an intense abdominal pain. The patients had weekly or daily seizures and after began TPM 1 patient stayed free from seizures, 5 improved more than 75% in frequency, 1 patient improved more than 50% and 3 had no control. A good control of seizures was achieved with a low dose of TPM as monotherapy and add-on therapy with carbamazepine even in severe cases.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Magnetic Resonance Imaging; Male; Topiramate; Treatment Outcome

Topiramate (TPM) is an antiepileptic agent, first licensed in the United Kingdom in 1994, that is used in the treatment of patients with refractory seizure disorders. TPM is a monosaccharide d-fructose derivate, with sulfamate function, and so far, few adverse side effects have been reported.. We describe three patients with epilepsy who were treated with TPM and developed hypohidrosis, heat and exercise intolerance, as well as fever. The sudomotor function was assessed after peripheral stimulation with pilocarpine iontophoresis.. Sweat response was reduced in all three patients. Signs and symptoms ceased after drug suppression.. This side effect associated with TPM, which has not been described previously, can be clinically significant during heat stress and exercise challenge.

Topics: Adolescent; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Fever; Fructose; Humans; Hypohidrosis; Infant; Male; Spasms, Infantile; Sweating; Topiramate

The present investigation reports cognitive improvement following withdrawal of topiramate (TPM) maintenance therapy in two patients with intractable seizures. The first patient received a neuropsychological evaluation after 10 months of adjunctive TPM treatment and was reassessed after complete withdrawal. The second patient received a first evaluation without TPM therapy. A reassessment was conducted after 13 weeks of stable TPM add-on therapy, and a third evaluation was performed after TPM withdrawal. During TPM treatment, the first patient demonstrated dysfunction on both verbal and non-verbal measures, suggesting bilateral impairment. Reassessment yielded cognitive improvement, and was consistent with a lateralized lesion as supported by seizure semiology, magnetic resonance imaging (MRI), and electroencephalogram (EEG) data. The second patient showed cognitive and emotional declines during TPM therapy. Reassessment, without TPM, demonstrated recovery on a majority of variables. These results illustrate the risk for considerable cognitive side effects after TPM habituation and support good recovery after withdrawal. Attempting to withdraw TPM and conducting a re-evaluation may be especially justified in the presence of a deflated neuropsychological profile that is inconsistent with a patient's estimated level of cognitive functioning. Reducing the influence of medical effects that could mimic bilateral dysfunction is particularly important in presurgical evaluations.

Topics: Adult; Anticonvulsants; Cognition; Drug Therapy, Combination; Emotions; Epilepsies, Partial; Female; Fructose; Humans; Male; Neuropsychological Tests; Remission Induction; Topiramate

Topiramate is a new anti-epileptic drug with proven efficacy against partial seizures in adults. A retrospective assessment of the use of topiramate in drug-resistant childhood epilepsy was undertaken. Thirty-four children (median age of 10 years; range 2-18 years) were treated for a median of 9 months (range 6-18 months). The starting dose was 0.25-2.0 mg/kg/day increasing to a maximum of 13 mg/kg/day. Generalized seizures occurred in 27 patients, partial seizures in 15 and infantile spasms in two. Epilepsies were localization-related in 15 patients and generalized in 18. One patient had severe myoclonic epilepsy in infancy. Two patients had Lennox-Gastaut syndrome, five (two currently and three previously) had West syndrome and one had epilepsy with myoclonic absences. Twenty patients had a substantial (> 50%) reduction in seizure frequency; two of whom became seizure-free. Two-patients had an increase in seizures. Efficacy was seen against simple and complex partial seizures, generalized tonic-clonic seizures (primarily generalized), atonic and tonic seizures, myoclonic seizures and infantile spasms. There was no response in the one patient with myoclonic absence seizures. Adverse effects were reported in nine patients; appetite suppression occurred in five patients, behaviour disturbances in three, somnolence in two and poor concentration in one patient. Topiramate is efficacious in a wide spectrum of childhood epilepsies and is well tolerated.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple; Epilepsies, Partial; Female; Fructose; Humans; Male; Spasms, Infantile; Topiramate; Treatment Outcome

Randomized, controlled studies of new antiepileptic drugs do not always highlight their best utilization in clinical practice. The authors gathered 361 cases of focal epilepsies treated with topiramate (TPM) as an add-on to other anti epileptic drugs prior to marketing. Among these, only 237 were treated for at least 3 months and analyzed here. These patients were treated by neurologists in a clinical setting, with free choice of associated drugs, titration and final daily doses. Compared with controlled studies, TPM was titrated slowly (mean rate: 43 mg/week, vs 100 to 200), and was given at a lower final dose (346 mg/d, vs 200 to 1000). This analysis confirmed the efficacy of TPM as add-on therapy in focal epilepsies (9.3p.100 totally controlled, 19 p.100 with reduction of seizures=90 p. 100, 52.7 p.100 responders at=50 p.100). It showed that there was a striking response in epilepsies originating from the central areas, which are often drug-resistant (19 p.100 totally controlled, 33.33 p. 100 with reduction of seizures=90 p.100). There were responders in all topographic groups. There was however no specific response according to etiology.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Drug Administration Schedule; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Multicenter Studies as Topic; Retrospective Studies; Statistics as Topic; Topiramate; Treatment Outcome

Randomized, controlled studies of new antiepileptic drugs are carried out following strict rules and do not always predict the drug's tolerability in clinical practice. The authors gathered 361 cases of focal epilepsies treated with topiramate (TPM) as an add-on to other antiepileptic drugs prior to marketing, in order to retrospectively analyze the incidence of adverse effects (AE). These patients had been treated by neurologists in a clinical setting, with free choice of associated drugs, titration and final daily dose. Compared with controlled studies, TPM was titrated slowly (mean rate: 43 mg/week, vs 100-200), and was given at a lower final dose (296 mg/d, vs 200 to 1000). This analysis shows that AE were less frequent and that TPM had an original tolerability profile, with CNS-related AE, often combined in the same patient (somnolence: 16. 1p.100, fatigue: 11.9p.100, mental slowing: 9.1p.100, slurred speech: 2,2p.100), and weight loss (14.7p.100 of patients, mean 4.5 kg or 6.6p.100 of body weight). Severe AE were uncommon (psychosis, 1; skin rash, 2; urinary lithiasis, 2). Withdrawal of TPM was caused by AE (13.6p.100), lack of efficacy (8.3p.100), aggravation of epilepsy (6.1p.100) or by a combination of these (5p.100). It is useful to use slow titration, in order to allow the greatest possible number of patients to benefit from its efficacy as an add-on drug in the treatment of resistant focal epilepsies.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Patient Dropouts; Retrospective Studies; Topiramate

Topiramate has been shown to be safe and effective in refractory partial epilepsy in children. Pharmacokinetic studies show that the clearance of topiramate is greater in children than in adults; therefore, higher doses may be needed in children than adults. It is generally well tolerated, except for cognitive dysfunction. Weight loss and the risk of renal stones can be significant in some cases. However, when compared with other anticonvulsant medications, topiramate has few serious idiosyncratic reactions such as rash, hematologic reactions, and hepatotoxicity.

Topics: Adult; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments.. In this single case study of a patient with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma.. The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD+/-0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD+/-0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD+/-0.06), and the correlation coefficient was 0.97.. Assuming a protein binding of TPM of approximately 13%. it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Extracellular Space; Female; Fructose; Humans; Microdialysis; Plasma; Skin; Subdural Space; Topiramate

Topiramate is a sulfamate-substituted monosaccharide that has demonstrated efficacy as an antiepileptic drug in adults with partial onset seizures. Experience in children has been limited, but early reports have supported its safety and effectiveness in children as young as 2 years of age. In two infants ages 12 and 9 months, respectively, with partial seizures, the authors report excellent efficacy with good tolerability at doses up to 7.7 mg/kg. Although long-term safety and possible adverse sequelae have not been fully established in children, topiramate may represent an option for infants with high seizure frequency unresponsive to standard antiepileptic drugs.

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Epilepsies, Partial; Fructose; Humans; Infant; Male; Retreatment; Topiramate; Treatment Outcome

The novel anticonvulsant topiramate has been shown to have efficacy across a range of seizure types including both generalized and partial seizures in several well-designed randomized controlled trials. It has also been shown to be effective in atonic seizures associated with Lennox-Gastaut syndrome. Tolerability data show a tendency to neuropsychiatric side-effects, such as confusion and word finding difficulties, when topiramate is used in polytherapy; these side-effects are reduced in monotherapy usage. The efficacy and spectrum of seizures treated by topiramate suggests that it has an important role in managing epilepsy in people with intellectual disability. The predictable side-effects can be monitored in clinical practice and possibly reduced by slow dose increments. The data set of patients with intellectual disability is still too small to rule out idiosyncratic drug reaction.

Topics: Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsies, Partial; Fructose; Humans; Intellectual Disability; Topiramate; Treatment Outcome

Topics: Acetates; Amines; Anticonvulsants; Child, Preschool; Cyclohexanecarboxylic Acids; Drug Resistance; Electroencephalography; Epilepsies, Partial; Epilepsy; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Infant; Lamotrigine; Male; Topiramate; Triazines

Topiramate is a new antiepileptic drug, which is not yet marketed in Germany. The anticonvulsive activity is probably mediated by sodium-channel blockade combined with gabaergic and weak antiglutamatergic properties. We investigated 23 patients with partial seizures in this open prospective study. The efficacy was analysed under stable concurrent antiepileptic drugs. Two of the patients became seizure free. Ten patients had a reduction of seizure frequency of at least 50%. The responder rate was 57%. The maximum daily dosages were 400 to 850 mg. Side-effects without relationship to dose were nervousness and aggression. In two patients an psychotic episode occurred. Dose-related side-effects were ataxia, dizziness, somnolence and dysarthria. This study is underlining that topiramate is efficacious in the treatment of partial onset seizures but also associated with a narrow therapeutic width.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Fructose; Humans; Male; Neurologic Examination; Prospective Studies; Topiramate; Treatment Outcome