Felbamate in refractory partial epilepsy

This open-label study was performed to evaluate efficacy and safety of Felbamate (FBM) add-on therapy in drug-refractory partial epilepsy. We evaluated 36 patients (12 males) aged 11-68 years (mean 29.8) in which FBM was titrated gradually from 300 mg/day to a mean total maintenance daily dose of 1936 mg. Patients were monitored according to clinical practice and performed regularly laboratory tests. Mean follow-up of FBM therapy was 10 months (range 2-27). In this study, 5% of patients resulted to be seizure-free, 11% showed a seizure reduction more than 75%, 23% decreased their seizure frequency between 50% and 75% (P = 0.0001). The adverse events which were reported more frequently were: nausea, vomiting, anorexia and weight loss. Even if the patients sample is small FBM proves its efficacy in partial epilepsy, showing a relatively well tolerated profile.     

Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes.

INTRODUCTION: Although vagus nerve stimulation (VNS) therapy is approved for the treatment of partial onset seizures, its efficacy for generalized seizures has not been fully evaluated. This Investigational Device Exemption assessed the outcome of VNS therapy among patients with generalized epilepsy syndromes. METHODS: Sixteen patients with pharmacoresistant generalized epilepsy syndromes and stable antiepileptic drug (AED) regimens were implanted with the VNS therapy device and were evaluated for changes in seizure frequency and type between baseline and follow-up of 12-21 months. RESULTS: The patients experienced a statistically significant overall median seizure frequency reduction of 43.3% (P = 0.002, Wilcoxon signed rank test) after 12-21 months of VNS therapy. Types of seizures that may involve a fall or collapse decreased with reductions in the frequency of myoclonic (60% reduction, n = 9; P = 0.016, Wilcoxon signed rank test), tonic (75% reduction, n = 8, NS), atonic (98.6%, n = 3, NS), and clonic seizures (86.7%, n = 1, NS). Conclusion: The benefits of reduced seizure frequency and reduced risk of injury merit consideration of VNS therapy for patients with pharmacoresistant generalized seizure syndromes.     

Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of D-α-Tocopherol (Vitamin E) as Add-on Therapy in Uncontrolled Epilepsy

Summary: In a double-blind, cross-over trial, vitamin E, and placebo were compared as add-on therapy in 43 patients with uncontrolled epilepsy. The study consisted of a 3-month baseline period followed by two treatment phases of vitamin E or placebo with cross-over to the second phase after 3 months. No significant side effects were noted during the study. Mean seizure frequency in the baseline period was 15.9 ± 10.5 as compared with 11.8 ± 10.9 during the placebo phase and 13.7 ± 11.1 during the vitamin E phase. No significant change in seizure frequency was observed with vitamin E as compared with placebo (p > 0.1). Similar observation was noted in subgroups with generalized seizures (n = 25), partial with secondarily generalized seizures (n = 11), or complex partial seizures (CPS) (n = 7). This study did not corroborate the earlier claims of therapeutic efficacy of vitamin E as add-on therapy in refractory epilepsy in adults.     

Lamotrigine add-on therapy for childhood-onset refractory epilepsy: comparison of the efficacy between 3 months and 6 months after initiation

We investigated the effect of lamotrigine (LTG) add-on therapy in 50 patients with childhood-onset refractory epilepsy (25 males and 25 females): 15 with localization-related epilepsy, 33 with generalized epilepsy, and 2 with undetermined epilepsy. Twenty-four patients had experienced a period of West syndrome during their clinical course. Age at the start of LTG therapy ranged from 2 years 6 months to 41 years 2 months: <16 years in 43 and > or = 16 years in 7. Seizure frequency was > or = 1 per day in 36 patients (72%) and > or = 1 per week in 14 (28%). We increased the LTG dosage every two weeks in accordance with usage recommendations. We evaluated efficacy at two points: 3 and 6 months after the start of LTG. At the 6-month point, seizure freedom was achieved in 2 patients (4%), > or = 50% seizure reduction in 14 (28%), 25 to 50% seizure reduction in 20 (40%), no effect in 6 (12%), and aggravation in 4 (8%). Only 4 patients (8%) stopped LTG therapy within 6 months due to LTG-related mild skin rash in 2 and suspicion of seizure aggravation in the other 2. In terms of seizure types, seizure freedom or > or = 50% seizure reduction was achieved in 29% for epileptic spasms, 32% for tonic seizures, and 29% for partial seizures. A comparison between the 3- and 6-month points revealed that the efficacy level was increased or maintained in 77% of the patients and decreased in 23%. In most cases, the highest level of efficacy appeared within 3 months with doses that were smaller than maintenance doses. Observed CNS-related adverse effects included somnolence in 16 patients, irritability in 14, and sleep disturbance in 11. Positive psychotropic effects in daily activities were seen in 28 patients (56%). These effects appeared regardless of the change in seizure frequency with doses that were smaller than maintenance doses.     

Felbamate for refractory absence seizures

We treated 10 patients (aged 5–37 years) with medically refractory absence seizures with felbamate (FBM). Average duration of absence seizures was 16.2 years. All patients continued to have absence seizures at maximally tolerated doses of valproic acid and/or ethosuximide. At maximal FBM dosage (45 mg/kg/day or 3,600 mg/day), there was at least a 65% reduction in absence seizure frequency in eight patients; in four, there was a > 95% reduction. Mean duration of FBM therapy is 16.2 months (range, 5–31 months). Nine patients remain on FBM. Two patients are on FBM monotherapy; seven others are on FBM and one or two other antiepileptic drugs. FBM was discontinued in one patient who developed severe insomnia followed by a return to baseline absence seizure frequency after an initial good response, and an increase in generalized tonic-clonic seizures (GTCS). Three other patients also had a history of GTCS; in one there has been no significant change, whereas two have not had a GTCS during FBM therapy. Eight patients continue to have a clinically meaningful reduced absence seizure frequency, and eight patients reported fewer adverse effects with their current regimen including FBM. Tachyphylaxis to the antiabsence efficacy was observed in four cases. These preliminary findings suggest that FBM is useful in treating absence seizures.     

Levetiracetam during 1-year follow-up in children, adolescents, and young adults with refractory epilepsy

PURPOSE: To evaluate the efficacy and safety of levetiracetam (LEV) in refractory crypto/symptomatic, partial or generalised epilepsy in children, adolescents and young adults. METHODS: We performed a prospective open label add-on study in 99 patients (age 12 months to 32 years, mean 14 years) with partial or generalised, crypto/symptomatic seizures. Levetiracetam was added to no more than two baseline AEDs and the efficacy was rated according to seizure type and frequency. RESULTS: LEV was initiated at the starting dose of 10mg/kg/day with 5-day increments up to 50 mg/kg/day, unless it was not tolerated. Concomitant therapy was generally not modified throughout the study. After a mean follow-up period of 6.7 months (range 3 weeks to 29 months), 11 patients (11.1%) were free of seizures (cryptogenic partial epilepsy, 5; symptomatic partial epilepsy, 6). A more than 75% seizure decrease was found in 14 patients (14.1%) and >50% in 8 (8.1%). Seizures were unchanged in 38 (38.4%), and worsened in 23 (23.2%). Mild and transient adverse side effects were found in 17 patients (17.2%), mostly represented by irritability and drowsiness. CONCLUSION: LEV appears to be well tolerated in children and adolescents with severe epilepsy and seems to be a broad spectrum AED, though in our experience, it was more effective against partial seizures with or without secondarily generalisation. LEV efficacy in other epilepsy syndrome should be evaluated further in homogeneous, more selected patients.     

Clinical experience of levetiracetam monotherapy for adults with epilepsy: 1-year follow-up study.

We identified 46 patients with a history of partial seizures, with and without secondarily generalization, who received levetiracetam (LEV) (Keppra) monotherapy. Patients began LEV either as first line therapy (n=11) or were converted to LEV monotherapy (n=35) after failing prior antiepileptic medications (AEDs). Patients were followed up to 12 months after LEV started. The majority of these patients were able to continue on LEV and a small number of patients discontinued LEV secondary to lack of efficacy. One third of the non-seizure free group at 6 months of follow-up had worse seizure control at 12 months and two thirds had the same or better seizure control. Our 1-year follow-up data of LEV as monotherapy suggests that LEV can be effective and well tolerated in adults with either new or difficult to control epilepsy. A prospective, large, long-term double-blind study is needed to confirm this finding.     

Long-term treatment with vigabatrin - 10 years of clinical experience.

This report describes the long-term follow-up of 56 patients with refractory partial epilepsy who, within 3 months of vigabatrin add-on therapy (3 g/day), showed a reduction in monthly seizure frequency of more than 50%. The short-term (6 months) and long-term (5 years) effects of vigabatrin on seizure frequency in this patient cohort have been published separately. The reduction in seizure frequency appeared to be long-lasting in the patients followed-up (n = 36) and, importantly, a significant number of the patients (n = 7) became seizure-free, especially during long-term treatment. Thus, the efficacy of vigabatrin appears to be progressive, at least in patients who show an early response to treatment. These results are consistent with experimental findings that suggest that vigabatrin may have anti-epileptogenic and neuroprotective effects.     

Long-Term Follow-Up of Stereotactic Lesionectomy in Partial Epilepsy: Predictive Factors and Electroencephalographic Results

We performed an extended follow-up study assessing the efficacy of stereotactic lesionectomy in 23 patients with foreign-tissue lesions and intractable partial epilepsy. Sixteen lesions involved functional or eloquent cortex as determined by anatomic localization. By definition, the surgical objective in these patients was excision of the lesion, and not the surrounding cerebral cortex. The mean duration of follow-up was 48.5 months (range 26-69 months). Seventeen patients (74%) had a significant reduction in seizures (greater than or equal to 90%) after lesionectomy. Thirteen patients (56%) had a class I operative outcome (seizure-free, single seizure episode, or auras only). Five of these patients were successfully discontinued from antiepileptic drug (AED) therapy. Patients with temporal lobe lesions were statistically less likely to be rendered seizure-free (p less than 0.05). Age at operation, duration of epilepsy, and underlying pathology were not significant predictors of seizure outcome. The anatomic distribution of extracranial EEG recorded epileptiform activity did not appear to be an important determinant of outcome. The absence of interictal epileptiform activity in the 3-month postoperative EEG correlated with a significant reduction in seizures. Long-term follow-up indicates that lesionectomy may be effective in select patients with medically refractory partial seizure disorders.     

Felbamate in the Treatment of Refractory Partial-Onset Seizures

Summary: Felbamate (FBM) is a new antiepileptic drug (AED) that has been tested in open and controlled studies in patients with therapy-refractory partial-onset seizures. Proof of efficacy is based on results of five controlled studies (three with polytherapy and two with monotherapy). In two of the three polytherapy studies, a classic placebo crossover design was used. The third study used a novel design evaluating the efficacy of FBM in a placebo-controlled parallel design in patients completing an evaluation for epilepsy surgery. The primary efficacy variable in this study was the number of patients who experienced a fourth seizure before the end of the study. Forty-six percent of patients randomized to FBM stopped treatment prematurely because of the occurrence of a fourth seizure compared with 88% randomized to placebo. Two studies investigating the efficacy in monotherapy were performed. Both studies used an identical trial design comparing FBM with a low dosage of valproate (VPA). The efficacy of FBM was found to be superior to the low-dosage VPA for both studies. Open long-term follow-up studies have confirmed the long-term efficacy of FBM for up to 12 months. Overall, FBM was well tolerated in both poly- and monotherapy.     

An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.

BACKGROUND: The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population.METHODS: LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg x day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and >or=50% responder rate. RESULTS: LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n=219) to 1.10 seizures per week during the evaluation period (n=191 patients with at least one seizure count during evaluation). The >or=50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year. CONCLUSION: LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.     

Clobazam monotherapy in drug na?ve adult patients with epilepsy.

PURPOSE: Evaluation of the efficacy and side effects profile of Clobazam in a 24-week open-labelled trial involving 26 cases of drug na?ve adult patients with epilepsy. METHODS: The study was an open labelled unicentre trial in which only drug na?ve cases with epilepsy were included. A total of 26 cases were recruited. One case was dropped because he did not complete the desired follow up. Seizure type and frequency were recorded and follow up was done at 4, 8, 12, 18 and 24 weeks after initiation of therapy. The change in seizure severity, the dose of Clobazam required and development of side effects were recorded. RESULTS: The seizure types included GTCS (n=16), complex partial seizures (n=4), focal motor seizures with secondary generalisation (n=3) and juvenile myoclonic epilepsy (n=2). Out of 25 patients, 16 (64%) became seizure free, while five (20%) had >50% reduction in their seizure frequency. Thus, these 21 patients (84%) were considered to be well controlled. The commonest side effect seen was sedation, which was noted in 4 of the 25 patients (16%). However, in none of these four patients sedation was significant enough to warrant stoppage of therapy. Weight gain, gait ataxia, loss of short-term memory and breakthrough seizures were noted in one patient each. CONCLUSIONS: The efficacy of Clobazam coupled with the lack of significant side effects noted in our study makes it merit consideration as monotherapy in adult patients with epilepsy.     

Epilepsy surgery in children with gliomatosis cerebri

PURPOSE: Gliomatosis cerebri (GC) is a rare neoplastic disorder that may present as intractable epilepsy during early life. We report our experience regarding the evaluation and the surgical treatment of epilepsy in this population. METHODS: All children evaluated between 1990 and 2006 for surgery of epilepsy (n = 741) with pathologically proven GC were selected. RESULTS: We identified four male children with age at seizure onset ranging from 4 months to 11 years. Two had hemiparesis and one child with infantile spasms was developmentally delayed. Seizures occurred daily (n = 3) or monthly (n = 1). Ictal semiology was consistent with psychomotor seizures (n = 1), partial motor seizures (n = 2), and asymmetric epileptic spasms (n = 1). Surgery was symptomatic and aimed at debulking and controlling the epilepsy. Procedure was individually tailored based on the presurgical evaluation. Brain MRI revealed widespread hemispheric involvement (n = 3) or infiltration of the temporal lobe and basal ganglia (n = 1). Two patients were initially misdiagnosed as hemispheric cortical dysplasia and hemimegalencephaly. Scalp EEG was nonlocalizing in two cases, showed a right temporal focus in one case, and was not performed in one case. Interictal SPECT in one patient revealed widespread hemispheric hypoperfusion. Three cases were resected under ECoG guidance after a mean delay of 11 months after seizure onset. Following functional hemispherectomy (n = 1) or focal cortical resection (n = 2), all children were alive and seizure free with a mean follow-up of 48 months (2-5 years). No unexpected complication was reported. One nonoperated case was alive but still seizing after 15 months follow-up. Chemotherapy was associated in three cases. CONCLUSIONS: GC is a rare cause of medically resistant epilepsy that may present in early life. The lack of a discrete lesion may lead to diagnostic uncertainty, especially in infancy. Epilepsy surgery is an effective therapy that can improve quality of life.     

Felbamate: A Clinical Trial for Complex Partial Seizures

We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM.     

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.     

Felbamate in the Treatment of Lennox-Gastaut Syndrome: Results of a 12-Month Open-Label Study Following a Randomized Clinical Trial

Summary: Felbamate (FBM) is a new antiepileptic drug (AED) that has been evaluated in partial seizures and in the Lennox-Gastaut syndrome (LGS). When tested against placebo in an add-on, randomized, double-blind trial in 73 children with LGS, FBM significantly reduced the frequencies of astatic (atonic) seizures and generalized tonic-clonic seizures plus total seizure counts. In addition, FBM-treated subjects improved significantly on a parent-rated global evaluation and had fewer injuries. Overall, ˜50% of subjects experienced a 50% or greater reduction in total seizure frequency and a dose-response relationship was apparent. The improvement that occurred in the double-blind study has been sustained for at least 12 months in subsequent open-label follow-up studies. In the first month of FBM treatment, 62% of the subjects who had previously received placebo had a reduction in total seizure frequency of >50%. By the 12-month follow-up point, approximately half of the patients had a 50% reduction in total seizure count. Astatic seizures responded even better, with two-thirds of patients having a reduction of >50% in astatic seizure frequency after 12 months of treatment. Based on adverse experience reports thus far, FBM appears to be well tolerated. FBM is the first drug to be shown effective in the LGS in randomized controlled trials. Although few subjects with LGS became seizure free, the frequency of the most severe seizure types decreased and the patients' global functioning improved.     

The influence of seizure type on the efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine

Plasma concentrations of phenytoin, phenobarbital, or carbamazepine were monitored prospectively during successful single-drug therapy in 78 patients who had various types of epileptic seizures. Mean plasma concentrations necessary for complete control of tonic-clonic seizures alone were as follows: phenytoin, 14 micrograms/mL (n = 28); phenobarbital, 18 micrograms/mL (n = 10); and carbamazepine, 5.5 micrograms/mL (n = 2). Epilepsy with simple or complex partial seizures alone or together with tonic-clonic seizures was completely controlled at the following plasma concentrations: phenytoin, 23 micrograms/mL (n = 25); phenobarbital, 37 micrograms/mL (n = 5); and carbamazepine, 7 micrograms/mL (n = 7). Higher plasma concentrations of phenytoin, phenobarbital, and carbamazepine are necessary for control in epilepsy with simple or complex partial seizures compared with epilepsy with tonic-clonic seizures alone. The efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine varies with the type of seizure.     

Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents

A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (< or = 3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.     

Efficacy and Tolerability of Vigabatrin in Children with Refractory Partial Seizures: A Single-Blind Dose-Increasing Study

Summary: The efficacy and tolerability of vigabatrin (VGB) in children with refractory partial epilepsy were assessed in a single-blind, add-on, fixed-sequence, placebo-controlled trial. After 1-month observation, the patients entered a 7-month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/kg/day, to be increased to 60 and 80 mg/kg/day at 2-month intervals if seizures persisted. Of the 46 children enrolled in the study, 7 dropped out prematurely due to lack of efficacy of the drug (n = 6) or increased seizure frequency (n = 1). In 11 patients who either became seizure-free (n = 3) or improved markedly (n = 8), treatment was completed at a dose <80 mg/kg/day. The average number of seizures per month in the 39 patients who completed the study decreased from 97 during placebo to 21,12, and 9 after 2, 4, and 6 months of VGB treatments respectively (p < 0.0001 at each time). Response to VGB remained statistically significant when dropouts were included in the evaluation. The number of patients who had <50% reduction in seizure frequency after 2, 4, and 6 months was 28, 33, and 35, respectively. Eight patients became seizure-free during the last 2 months of VGB treatment (3 at 40, 3 at 60, and 2 at 80 mg/kg/day, as compared with none during placebo treatment). Serum levels of associated antiepileptic drugs (AEDs) showed no signscant changes, except for serum phenytoin (PHT) concentration, which significantly (p < 0.01) decreased after VGB treatment. Increased appetite and sedation were observed in 17 and 11% of cases, respectively. VGB is effective in the management of refractory partial epilepsy in children, and in some patients a positive dose-response relationship appears to occur over the assessed dosing range.     

Felbamate monotherapy: controlled trial in patients with partial onset seizures.

Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single-center, randomized, double-blind, parallel-group trial. During the 56-day baseline period, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one-third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria. Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in highest 2-day seizure frequency, single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria (p less than 0.001, chi-square test). When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile.