topiramate and Epilepsies--Myoclonic

The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS) in Germany with routine antiepileptic drugs (AEDs) and emergency medication, and to review the literature of real-world evidence on medicine utilization of patients with DS in Europe.. Patient use of routine AEDs and emergency medications over 3-6 months was analyzed from a 2018 multicenter survey of 93 caregivers of patients with DS throughout Germany. Results were contextualized in a review of real-world evidence on medicine utilization of patients with DS in Europe.. The variety of medications and the most frequent combinations routinely used by patients with DS (AEDs and others) are described. Patients use a large number of pharmaceutical treatments to manage seizures. The five most commonly used AEDs were sodium valproate (66% of the patients; mean daily dose: 660 mg; 24.5 mg per kg bodyweight), bromide (44%; 1462 mg; 51.2 mg per kg), clobazam (41%; 10.4 mg; 0.32 mg per kg), stiripentol (35%; 797 mg; 27.6 mg per kg), and topiramate (24%; 107 mg; 3.5 mg per kg). Ninety percent had reported using emergency medications in the last 3 months;, with the most common medications being Buccolam (40%, an oromucosal form of midazolam) and diazepam (20%, mostly rectal application). No discernable relationships between current medication and age or seizure frequency were observed.. This is the first comprehensive report of routine AEDs and emergency medication use in a large sample of patients with DS in Germany over a period of 3-6 months and shows that despite the most common AED combinations being in line with clinical guidelines/best practice, there is no discernable impact of best treatment on seizure frequency. We find a higher use of bromide in Germany compared with other real-world evidence in Europe.

Topics: Anticonvulsants; Clobazam; Cohort Studies; Drug Prescriptions; Drug Therapy, Combination; Epilepsies, Myoclonic; Female; Germany; Humans; Male; Seizures; Topiramate; Valproic Acid

Dravet syndrome (DS) is one of the most pharmacoresistant epilepsy syndromes. Valproate is used as a first-line agent to prevent the recurrence of febrile seizures and oral/nasal/rectal benzodiazepine is used for any long-lasting seizures, but these agents are most often insufficient. Lamotrigine, carbamazepine, and high doses of intravenous phenobarbital should be avoided because they may worsen seizures. Topiramate, levetiracetam, bromide, and the ketogenic diet may provide substantial efficacy as adjunctive therapy/procedure. Stiripentol is the only compound that proved its efficacy in DS through two independent randomized placebo-controlled trials, when combined with valproate and clobazam. Their dose has to be decreased to minimize the side effects (mostly loss of appetite) resulting from pharmacokinetic interactions of stiripentol powerfully inhibiting cytochromes P450. Stiripentol acts as a γ-aminobutyric acid (GABA)ergic agent, mainly via the α3 subunit of GABA(A) receptors. Stiripentol (Diacomit) was approved as an orphan drug in 2007 in Europe for adjunctive therapy in DS. Up to now, >500 children have been safely treated, and recent experiment in Japan confirmed stiripentol benefit in DS children with comedications other than valproate and clobazam. Because early status epilepticus is likely to negatively impact cognitive outcome, we recommend the introduction of stiripentol as soon as the diagnosis of DS is clinically confirmed. Topiramate and the ketogenic diet are alternatives in pharmacoresistant cases.

Topics: Anticonvulsants; Diet, Ketogenic; Epilepsies, Myoclonic; Fructose; Humans; Syndrome; Topiramate; Treatment Outcome

Treatment of the catastrophic epilepsies [infantile spasms (IS), Lennox-Gastaut syndrome (LGS), and progressive myoclonic epilepsy (PME)] remains a challenge to clinicians. For IS, adrenocorticotropic hormone has traditionally been the drug of choice in the United States but may be associated with serious side effects in some patients. Vigabatrin has shown promise in treating IS patients, particularly those with tuberous sclerosis. However, the drug is associated with visual field loss and is not commercially available in the United States. Newer antiepilepsy drugs (AEDs), such as zonisamide, topiramate (TPM), and lamotrigine (LTG), may be useful in patients with IS. Although LTG, TPM, and felbamate are approved in the United States for the treatment of LGS, the overall effectiveness of therapy in patients with LGS is poor. For PME, valproate is a first-line treatment. Zonisamide and levetiracetam also show promise. Supplementation with certain cofactors to correct deficiencies and increase mitochondrial function may be useful in some patients with PME, but response to such therapy is not well documented. Advances in our understanding of the etiologies, mechanisms, and genetics underlying the catastrophic epilepsies may facilitate more effective pharmacologic interventions.

Topics: Anticonvulsants; Child, Preschool; Epilepsies, Myoclonic; Epilepsy; Fructose; Humans; Infant; Isoxazoles; Lamotrigine; Spasms, Infantile; Topiramate; Treatment Outcome; Triazines; Vigabatrin; Zonisamide

This study was to evaluate the efficacy and safety of topiramate (TPM) in patients with severe myoclonic epilepsy in infancy (SMEI) and refractory seizures.. We performed a prospective multicentric open label add-on study in 18 patients (age 2-21 years, mean 9 years) with SMEI and refractory seizures of different types. TPM 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/24 h up to a maximum daily dose of 12 mg/kg. After a mean period of 11.9 months (range 2-24 months), three patients (16.7%) had 100% fewer seizures and ten patients (55.5%) had a more than 50% seizure decrease. In no patient there was a seizure worsening. Mild to moderate adverse events were present in four patients (22.2%), represented by weight loss, hypermenorrhoea, renal microlithiasis, nervousness and dysarthric speech.. TPM may be a useful drug in patients with SMEI, being particularly effective against generalized tonic-clonic seizures. Further studies are needed to evaluate the early use of this drug in such a severe syndrome.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Epilepsies, Myoclonic; Female; Fructose; Humans; Italy; Male; Prospective Studies; Topiramate

At a tertial referral epilepsy centre 39 children were consecutively enrolled in an open add-on study with topiramate (TPM). All children had intractable epilepsy; the mean seizure frequency was 36 per month, and 31 children were treated with polypharmacy. All but five children were mentally retarded. The initial dose of TPM was 0.5-1 mg/kg daily, slowly titrated with 1-3 mg/kg daily every second week with an estimated target dose of 10 mg/kg daily. At latest follow-up 19 children continued on TPM, three (8%) were seizure-free, eight (21%) had a seizure reduction of more than 50% and eight (21%) improved their general condition. Mean follow-up was 13 months (range 9-36 months). Seizure reduction was seen in focal as well as generalized epilepsies. Adverse effects were reported in 21 cases (54%), weight loss and sedation being most frequent. The mean steady state dose in the children continuing on TPM was at latest follow-up: 14 mg/kg daily (< 5 years), 10 mg/kg daily (5-7 years), 5.8 mg/kg daily (8-17 years). The corresponding plasma level varied from 3 to 45 mumol/litre, and a significant correlation between the daily dose in mg/kg and the plasma level was found. Two patients with progressive myoclonus epilepsy are described separately; one had a dramatic general improvement. It is concluded that TPM seems to be a promising new broad-spectrum anti-epileptic drug, which is efficacious even in epilepsy syndromes, intractable to other new anti-epileptic drugs such as vigabatrin and lamotrigine.

Topics: Adolescent; Anticonvulsants; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsies, Myoclonic; Epilepsy; Female; Fructose; Humans; Male; Topiramate; Treatment Outcome

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

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

Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its ac

Topics: Adult; Anticonvulsants; Cannabidiol; Child; Clobazam; Drug Therapy, Combination; Epilepsies, Myoclonic; Epileptic Syndromes; Fenfluramine; Humans; Sleepiness; Spasms, Infantile; Topiramate

Dravet syndrome (DS) is an intractable epilepsy syndrome. The three-drug combination therapy of sodium valproate (VPA), clobazam (CLB) and stiripentol (STP) is recommended worldwide.. We present a case of DS, in which treatment with CLB could not be continued because of the appearance of adverse reactions to it. Replacement with topiramate (TPM) proved to be markedly effective.. It is suggested that combination therapy with VPA, TPM and STP is for DS epilepsy.

Topics: Anticonvulsants; Child, Preschool; Dioxolanes; Drug Therapy, Combination; Epilepsies, Myoclonic; Epilepsy; Female; Fructose; Humans; Topiramate; Valproic Acid

Stiripentol (STP), valproate (VPA) and topiramate (TPM) are reported to have efficacy for Dravet syndrome. In this study, we sought to elucidate the mechanisms underlying the increased serum VPA concentrations following STP adjunctive therapy in patients with Dravet syndrome.. Twenty-eight patients with Dravet syndrome (age range, 1-35 years) undergoing combination therapy with VPA and STP were included in this study. We evaluated VPA and clobazam (CLB) serum concentrations before and after add-on STP. We also investigated potential factors impacting VPA metabolism during add-on STP therapy, including add-on TPM and CYP2C9 and CYP2C19 gene polymorphisms. The effect of STP on the metabolism of concomitantly administered CLB was also investigated.. Add-on STP was significantly associated with the serum concentration-to-dose (CD) ratio of VPA. Two patients, who were concomitantly treated with TPM, developed severe anorexia and thrombocytopenia because of marked increases in serum VPA concentrations. Further analysis revealed that the rate of increase in the VPA CD ratio was positively correlated with TPM dose. In patients not receiving TPM, STP enhanced the rate of increase in the VPA CD ratio to a significantly greater extent in CYP2C19 extensive metabolizers than in CYP2C19 poor metabolizers. Add-on STP was also associated with significant increases in CLB and N-desmethyl-CLB serum concentrations.. Our findings suggest that serum VPA concentrations should be carefully monitored during STP adjunctive therapy, particularly in patients receiving concomitant TPM therapy.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Clobazam; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Dioxolanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Myoclonic; Female; Fructose; Humans; Infant; Male; Polymorphism, Genetic; Retrospective Studies; Topiramate; Valproic Acid

There is strong evidence for the use of the ketogenic diet (KD) in Dravet syndrome (DS). The purpose of this study was to evaluate both effectiveness and tolerability in comparison with various antiepileptic drugs (AEDs).. 32 children (19 males) with genetically confirmed DS treated at our center since 1999 were analyzed retrospectively. Data collected from patients' files included type of mutation, age at treatment initiation and treatment lag, overall seizure frequency and frequency of different seizure types, especially prolonged seizures and status epilepticus (SE). Efficacy and safety of the KD were evaluated. In addition, the effect on seizure count was compared with that of various AED regimen and the vagus nerve stimulation (VNS).. Overall response to the KD was 70% at 3 months and 60% at 12 months. No SE occurred while patients were on the diet, and the frequencies of prolonged generalized and myoclonic seizures were reduced. No severe side effects requiring withdrawal of the KD were observed. Although the effect of the KD was independent of age at initiation, it had to be withdrawn due to noncompliance more frequently in solid fed older children compared with infants treated with the liquid ketogenic formula. The KD was not significantly inferior to the current gold standard AED triple combination of Stiripentol+Valproate+Clobazam (89%), Bromides (78%), Valproate alone (48%), Topiramate (35%) and VNS (37%) and significantly more effective than Levetiracetam (30%; p=0.037, Pearson's Chi-square).. These data suggest that the KD ranks among currently used AEDs as an effective treatment for seizures in DS. According to our results (good effect on SE and prolonged seizures, good tolerability, less compliance problems due to formula treatment) the KD should be considered as an early treatment option in infants with DS.

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Bromides; Child; Child, Preschool; Clobazam; Diet, Ketogenic; Dioxolanes; Epilepsies, Myoclonic; Female; Fructose; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Vagus Nerve Stimulation; Valproic Acid; Young Adult

Till now truncation mutations of voltage-gated sodium channel alpha subunit type I (SCN1A) gene were mostly found in severe myoclonic epilepsy of infancy (SMEI) patients. In this research we first identified two novel de novo truncation mutations (S662X and M145fx148) in two patients whose phenotypes were quite milder compared with SMEI patients. One patient was diagnosed as generalized epilepsy with febrile seizures plus (GEFS+); the other had focal seizures. Both patients had good response to anti-epileptic therapy (valproate or the combination of valproate and topiramate). Our findings extended the utility of the SCN1A gene testing and further confirmed the complex relationship between genotype and phenotype of SCN1A mutations. Further work is needed to optimize the protocol for specific genetic testing in children with epilepsy.

Topics: Adolescent; Anticonvulsants; Base Sequence; Child, Preschool; Chromatography, High Pressure Liquid; Epilepsies, Myoclonic; Female; Fructose; Humans; Infant; Male; Molecular Sequence Data; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Nerve Tissue Proteins; Pedigree; Phenotype; Sodium Channels; Topiramate; Valproic Acid

Dravet syndrome is a rare, but highly refractory epilepsy syndrome. As conventional drugs are not effective, introduction of new effective drugs in clinical use will benefit patients with this disease. We assessed the effectiveness of topiramate (TPM) as adjunctive therapy in 11 patients with Dravet syndrome. TPM was started at doses ranging from 10 to 50 mg/day (0.57 to 2.0 mg/kg/day), and the dosage was increased gradually up to the maximum dose (9 mg/kg/day) depending on efficacy and tolerability. The frequencies of convulsive seizures (generalized tonic-clonic seizures, unilateral seizures, partial onset generalized tonic-clonic seizures) during two months before starting TPM, two months after starting TPM, and the fifth and sixth months after starting TPM were determined. The mean dose (mean +/- SD) of TPM at the second month was 2.7 +/- 1.5 mg/kg/day (1.0-5.7 mg/kg/day, n= 11), and that at the sixth month was 4.5 +/- 2.2 mg/kg/day (1.0-7.3 mg/kg/day, n=10). Evaluation at the second month revealed that one of 11 patients (9%) became seizure-free, six patients (54%) showed greater than 50% seizure reduction, three patients (27%) showed less than 50% seizure reduction, and one patient (9%) had aggravation of convulsive seizures resulting in discontinuation of TPM at the first month. Evaluation at the sixth month revealed that one of 10 patients (10%) was seizure-free, seven patients (70%) had greater than 50% seizure reduction, two patients (20%) had less than 50% seizure reduction, and no patient (0%) had aggravation. Adverse effects were observed in five patients; dizziness in three patients, sleepiness in three patients, and oligohidrosis in one patient. In the present study, TPM was useful as an adjunctive therapy to reduce the frequency of convulsive seizures in patients with Dravet syndrome. A large-scale efficacy study of TPM for Dravet syndrome is warranted.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsies, Myoclonic; Female; Fructose; Humans; Infant; Male; Topiramate; Young Adult

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

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

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

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

The objective of this study was to evaluate the interaction of the novel antiepileptic drug (AED), topiramate (TPM), with conventional AEDs against amygdala-kindled seizures in rats and pentylenetetrazol-induced convulsions in mice.. Experiments were performed on mice and fully kindled rats. In pentylenetetrazol test, the chemoconvulsant was used at its CD97 dose of 105 mg/kg, producing clonic seizures in 97% of mice. Adverse effects were evaluated with the chimney test and passive avoidance task. Plasma levels of AEDs were measured with immunofluorescence.. TPM at 20 mg/kg exerted a significant anticonvulsant effect as regards seizure and afterdischarge durations in amygdala-kindled seizures in rats, being ineffective at lower doses. Coadministration of TPM (10 mg/kg) with valproate (VPA; at a subtherapeutic dose of 50 mg/kg) resulted in essential reductions of seizure and afterdischarge durations. TPM (10 mg/kg) combined with carbamazepine (CBZ; at a subtherapeutic dose of 15 mg/kg) significantly increased afterdischarge threshold, simultaneously decreasing the remaining seizure parameters (duration or severity of seizures and afterdischarge duration). TPM (10 mg/kg) given with phenobarbital (PB; 15 mg/kg) markedly shortened seizure severity and seizure and afterdischarge durations. Combinations of TPM with diphenylhydantoin (PHT) were ineffective against kindled seizures in rats. TPM combined with VPA and PB did not alter their plasma levels, but its combination with CBZ resulted in an increased free plasma CBZ concentration. TPM (10 and 20 mg/kg) alone and its combinations with conventional AEDs affected neither motor coordination nor long-term memory, evaluated in the chimney and passive avoidance tests, respectively, in rats. In pentylenetetrazol-evoked convulsions in mice, TPM (175 and 200 mg/kg) showed anticonvulsant effects per se. Moreover, TPM (at its subtherapeutic dose of 150 mg/kg), significantly potentiated the anticonvulsant action of ethosuximide (ESM), but not that of VPA, PB, or clonazepam (CZP) against pentylenetetrazol-induced seizures. Either TPM alone (150 mg/kg) or its combination with ESM did not result in significant undesired effects.. The experimental data indicate that except for PHT, the combinations of TPM with conventional AEDs are beneficial against amygdala-kindled seizures in rats. In the pentylenetetrazol test, this novel AED potentiated only the protection offered by ESM.

Topics: Amygdala; Animals; Anticonvulsants; Convulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Complex Partial; Fructose; Kindling, Neurologic; Male; Mice; Pentylenetetrazole; Rats; Seizures; Topiramate

The aim of this study was to assess the effectiveness of topiramate (TPM) as an add-on regimen in reducing seizure rate in a population sample of patients diagnosed with severe myoclonic epilepsy in infancy (SME). Eighteen patients were evaluated. The mean observation time was 10.5 months (range, 6-18 months). Seizure frequency and type were recorded. Topiramate was administered as an add-on regimen at a starting dose of 1 mg kg(-1)and titrated to a maximum of 6-8 mg per kg per day. Different escalation rates were used, mainly weekly or fortnightly increments of dose. Three patients (16.6%) became seizure free, and 10 (55.6%) had a >50% reduction in seizure frequency: six of them (22.2%) achieved a reduction greater than 75%. Side-effects were observed in nine patients, eight with a weekly titration schedule and one with a fortnightly schedule. TPM is effective as adjunctive therapy for SME. Side-effects were mild and transient, generally related to rapid dosage titration.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Topiramate; Treatment Outcome

To study the effectiveness and safety of topiramate in clinical practice, for a group of patients with childhood onset epilepsy.. All patients treated with topiramate at the three study centers between November 1995 and December 31, 1997 were analyzed retrospectively, using a standardized study protocol. Data were gathered on demographic features, seizures response and medication related adverse events.. Eighty-seven patients were treated with topiramate. Over 90% seizure reduction was achieved in 8 (9%) patients, 50%-90% in 21 (24%), < 50% in 54 (62%) patients. Four patients (5%) had a deterioration in seizure control. Adverse events required topiramate discontinuation in 36 (41%). Of these 27 (31%) complained of unacceptable cognitive dulling. The rate of dose escalation and final dose in mg/kg were similar in those who remained on topiramate and those who were intolerant because of cognitive side effects.. Although topiramate resulted in > 50% seizure reduction in 29 (33%) of this group of patients with difficult epilepsy, its usefulness was limited by a high incidence of adverse effects. Adverse events prevented ongoing therapy for 36 (41%) and cognitive dulling resulted in topiramate discontinuation by 27 (31%) of the group.

Topics: Adolescent; Age of Onset; Anticonvulsants; Child; Child, Preschool; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Absence; Epilepsy, Complex Partial; Epilepsy, Generalized; Fructose; Humans; Infant; Retrospective Studies; Topiramate