Discontinuation of Phenytoin, Carbamazepine, and Valproate in Patients with Active Epilepsy

The effects of discontinuing individual antiepileptic drugs (AEDs) in patients with active epilepsy who are receiving combination therapy have not been studied systematically. We report a double-blind, prospective study of discontinuation of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) in 70 patients with chronic active epilepsy. Each drug discontinuation was randomized to one of two relatively fast rates of reduction, and a control group of 25 patients continued with stable therapy. Patients who had CBZ removed had a significant increase in seizures that was maintained for 4 weeks after the end of drug reduction, and 10 of these 23 patients had to restart therapy with CBZ. There was no significant change in seizure numbers in the other groups. Two patients discontinued from VPA had to restart the drug; none had to restart PHT. The optimal rates of reduction of CBZ remain uncertain. There was no evidence for a clinically or temporally distinct burst of "discontinuation seizures" in any group. Any marked increase in seizures always resolved on reintroduction of the discontinued drug.     

Antiepileptic Drugs and the Electroencephalogram

The usefulness of electroencephalography (EEG) as an aid to diagnosis of seizure disorders is established, but its role as a guide to monitoring treatment is much less certain. For those patients with classical absences and 3-s spike wave activity there is a very close correlation between control of clinically detected seizures and EEG events. In some, but not all, patients with other seizure disorders there is a positive correlation between numbers of seizures and amount of interictal epileptiform activity (IEA). Intravenous benzodiazepines and phenytoin result in both acute seizure control and suppression of IEA. For seizures other than absences, and antiepileptic drugs (AEDs) given in the medium and long term, there is generally not a clear relationship between control of seizures and IEA. In studies of children whose epilepsy is in remission, persistent IEA has been associated with a higher risk of seizure relapse should AEDs be discontinued, but in adults the relevance of persistent IEA appears to be much less certain. Benzodiazepines and barbiturates result in increased fast activity. All AEDs may result in slowing of the dominant rhythm and increased slow activity. Carbamazepine, in particular, is often associated with apparent deterioration of background activity, even in the face of clinical improvement. Further studies are necessary to determine the mechanisms and significance of AED-induced changes in EEG background activity.     

Computerized analysis of EEG background activity in mono-therapeutic patients with epilepsy--relationships between antiepileptic drugs and types of seizures

EEG background activity influenced by antiepileptic drugs (AED) was studied in 109 monotherapy and drug-free epileptic patients using t-Statistical Significance Probability Mappings (t-SPMs). Patients taking phenobarbital (PB) had an increase in alpha 1 and a decrease in alpha 2 activity in comparison with drug-free epileptics. Patients taking PB for generalized seizures with tonic-clonic convulsion only (GTC) also had a significant increase in alpha 1 and a decrease in alpha 2, whereas those with partial seizures (PS) had an increase in theta and beta 1 and a decrease in alpha 2 activity. Patients taking valproic acid (VPA) had a decrease in only beta 1 activity. Patients taking VPA for GTC showed an increase in delta activity, but those with PS did not show any changes. Patients taking carbamazepine (CBZ) for PS exhibited marked slowing with an increase in theta and alpha 1 and a decrease in alpha 2 activity. These results mean that changes in EEG due to AEDs differ depending on the type of seizures. More interestingly, discrepancy between EEG background activity and effects of AEDs was found: In PS type of seizures, the most effective CBZ exhibited striking slowing, PB was next, and VPA was last. In GTC, VPA resulted in greater slowing than PB.     

Efficacy of Nafimidone in the Treatment of Intractable Partial Seizures: Report of a Two-Center Pilot Study

Nafimidone is a potential new antiepileptic drug with a therapeutic profile in experimental animal seizure models similar to that of phenytoin (PHT). We report here the first clinical trial of nafimidone in epileptic patients. Twelve adult male patients with a mean of four or more medically intractable seizures per month were enrolled in a 14-week pilot study. Patients were stabilized on therapeutic levels of PHT and carbamazepine (CBZ) (nine patients) or on PHT alone (three patients) before entering a 4-week baseline period. Nafimidone, to a maximum dose of 600 mg/day, was added during 2 weeks in hospital. Patients were then evaluated weekly for 8 weeks. Eight patients experienced 33-98% improvement in seizure control. Three others did not show significant change in seizure frequency but experienced sufficient subjective improvement that they continued into long-term follow-up. One patient, who had a 63% improvement in mean weekly seizures during the pilot study, declined to continue. Thus, 10 patients entered long-term follow-up. Six of the 10 sustained 53 to greater than 99% improvement in seizure control compared with baseline over the course of 46-53 weeks of follow-up. Nafimidone had a marked inhibitory effect on the clearance of CBZ and PHT, resulting in higher plasma levels in nine patients. The possible role of the elevated CBZ levels in the apparent efficacy of nafimidone is discussed.     

Relationship of Carbamazepine Reduction Rate to Seizure Frequency During Inpatient Telemetry

Summary: To establish guidelines for medication reduction during inpatient telemetry, the records of 18 children and young adults with refractory partial seizures undergoing carbamazepine (CBZ) reductions during continuous video/EEG telemetry were reviewed. Six patients were receiving CBZ monotherapy, and 12 patients were treated with an additional antiepileptic drug (AED) maintained at baseline dosage during CBZ taper. Despite relatively rapid mean reductions in dosage of 44% by day 2 of taper, no patients experienced frequent repetitive seizures or status epilepticus (SE). Seizure rate during the entire CBZ reduction period correlated significantly with rate of drug reduction. Linear regression analysis showed drug reduction rate to be a good predictor of seizure rate. Fourteen patients experienced at least three seizures during CBZ taper. On the average, the third seizure occurred on day 5 of taper at a percentage of dose seduction of 79%. In 8 patients, CBZ concentrations were measured both before taper and ≤24 h after the third seizure. For these patients, seizure rate also correlated significantly with reduction in CBZ level. We conclude that manipulation of CBZ dose reduction rate is important in maximizing seizure frequency during telemetry and, in our patients, a relatively rapid rate of dose reduction was safe and effective in promoting seizure recordings.     

Gabapentin-induced modulation of interictal epileptiform activity related to different vigilance levels.

OBJECTIVES: Gabapentin (GBP) is a novel antiepileptic drug (AED), currently used as add-on therapy in patients with partial seizures. Similar to other AEDs, little is known about its effects on nocturnal sleep, despite the strict relationship between sleep and epileptic discharges. The aim of our study was to evaluate the effects of chronic therapy with GBP on both nocturnal sleep and on interictal epileptiform abnormalities (IEA) in relation to the different sleep stages. METHODS: Eighteen patients affected by partial seizures resistant to common AEDs were submitted to nocturnal polygraphic recordings under baseline conditions and after 4 months of add-on GBP treatment. RESULTS: We observed a significant increase in unilateral/focal IEA during light NREM sleep and a significant reduction in bilateral/diffuse IEA during wakefulness after sleep onset (WASO) with respect to the baseline condition. A significant increase in REM sleep and slow wave sleep (SWS) associated with a reduction in the number of awakenings and Stage 1 was also observed after GBP chronic therapy. CONCLUSIONS: GBP therapy improves the sleep pattern of epileptic patients and it seems to modulate the expression of IEA with different effects in relation to the various vigilance levels.     

Nocturnal Sleep and Daytime Somnolence in Untreated Patients with Temporal Lobe Epilepsy: Changes After Treatment with Controlled-Release Carbamazepine

Summary: Purpose: To define sleep disturbances in patients with temporal lobe epilepsy (TLE) and explore the association between carbamazepine (CBZ) therapy, sleep, and daytime somnolence.
Methods: We recorded nocturnal polysomnography and measured subjective and objective daytime somnolence in a group of newly diagnosed TLE patients, who had no evidence of anatomic brain lesion on neuroimaging and had never been treated before. Recordings were performed at baseline, after the initial administration of 400 mg CBZ-controlled release (CR) and after 1 month of treatment (400 mg twice daily b.i.d.). The findings were compared with those of a group of young healthy volunteers, both at baseline and after the first administration of CBZ. The chronic effect of CBZ-CR treatment was evaluated only in TLE patients.
Results: At baseline, nocturnal sleep patterns of TLE patients did not show marked alterations when the influence of seizures, cerebral lesions, and drugs had been ruled out. In both the TLE and the control groups, initiation of CBZ therapy provoked a reduction and a fragmentation of rapid eye movement (REM) sleep and an increase in the number of sleep stage shifts. In the TLE group, these effects were almost completely reversed after 1 month of treatment, and no significant difference was noted between baseline condition and long-term follow-up. With regard to daytime sleepiness, initial administration of the drug caused an increase in objective sleepiness only in the control group. Subjective sleepiness was higher in the control group than in the TLE group but was not modified by the drug.
Conclusions: We conclude that CBZ-CR has negative effects on REM sleep during initial administration but chronic treatment does not significantly modify nocturnal sleep or daytime somnolence.     

Significance of postoperative electroencephalograms in patients with extratemporal lesional epilepsy

We retrospectively studied EEGs performed 1 week, 3 months, and 1 year after surgery (lesionectomy or lesion resection with corticectomy) in 24 patients with extratemporal lesional epilepsy who had a mean duration of follow-up of 2.5 years. All patients had intractable partial seizures and underwent a comprehensive presurgical evaluation including long-term EEG monitoring. Twenty of the 24 patients had interictal epileptiform activity (IEA) identified on the preoperative sleep and awake EEG recordings. The presence of IEA 1 year after surgery was associated with recurrent seizure activity (p < 0.05). The postoperative EEG recordings, however, revealed no IEA in the two patients with persistent seizures who had no epileptiform abnormality on the preoperative study. The extent of cortical resection appeared to have no significant effect on the recording of IEA after surgery. One-year postoperative EEG recordings are prognostically useful in patients with extratemporal lesional epilepsy who undergo surgical treatment.     

Oxcarbazepine in Focal Epilepsy and Hepatic Porphyria: A Case Report

PURPOSE: Despite the development of new antiepileptic agents (AEDs), the therapy of epilepsies along with hepatic porphyrias remains difficult. Most AEDs such as carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) may precipitate clinically latent porphyria by inducing hepatic metabolism and increasing hepatic heme synthesis. Actually, only gabapentin (GBP), an AED without any hepatic metabolism, is known as a potential therapy for partial seizures in patients having hepatic forms of porphyria. METHODS: We present the case of a 28-year-old man with porphyria cutanea tarda (PCT) who has had pharmacoresistant epilepsy with complex partial and secondarily generalized seizures since early childhood. Despite having undergone several AED therapies over the years, no seizure-free interval had been observed. Only CBZ could cause a seizure reduction, but this treatment had to be discontinued as an elevation of the transaminases as well as pruritus and erythema were noted. The patient was then started on oxcarbazepine (OCBZ), a ketoanalogue of CBZ similar in its pharmacologic mechanism as well as its clinical use, but which, in contrast to CBZ, has only a low hepatic induction of microsomal enzymes. A final maintenance dose four times higher than that of CBZ was prescribed. RESULTS: In the follow-up, the patient stopped having seizures, and his liver functions became normal. CONCLUSIONS: It can be concluded that OCBZ can successfully be administered to patients with hepatic porphyria and focal epilepsy who did not respond to treatment with GBP.     

Comparative bioavailability of carbamazepine from two slow-release preparations.

In order to compare the multiple-dose bioavailability of carbamazepine (CBZ) from 2 slow-release preparations, Neurotol slow and Tegretol Retard, a single-blind, randomized, cross-over study was carried out. 21 adult patients with epilepsy were enrolled in the study. At the end of both 2-week treatment periods, a blood sample series was drawn after the administration of the morning CBZ dose. The serum concentrations of CBZ, CBZ-10,11-epoxide (CBZE) and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZD) were measured using HPLC. The mean bioavailability of CBZ from Neurotol slow was 11% (P = 0.002) higher than from Tegretol Retard. Owing to the better bioavailability, the peak (Cmax), lowest (Cmin) and mean (Css) concentrations of CBZ were also significantly higher during Neurotol slow treatment. Fluctuation of serum CBZ concentrations (Cmax-Cmin/Css, ADCss/AUC0-12h) did not differ significantly between the 2 treatments; neither did tmax. Similar results were obtained with CBZE and CBZD. There were more epileptic seizures on Tegretol Retard than on Neurotol slow, but the difference was not statistically significant. We conclude that there are significant differences in the bioavailability of CBZ from these 2 slow-release preparations.     

Oxcarbazepine, not its active metabolite, potentiates GABAA activation and aggravates absence seizures

Purpose:   Studies in genetic absence epileptic rats from Strasbourg (GAERS) indicate that enhancement of γ aminobutyric acid (GABA_A) receptor activity is a critical mechanism in the aggravation of seizures by carbamazepine (CBZ). We examined whether structural analogs of CBZ, oxcarbazepine (OXC), and its active metabolite, monohydroxy derivative (MHD), also potentiate GABA_A receptor current and aggravate seizures.
Methods:   In vitro studies in Xenopus oocytes compared the three drugs' effect on GABA_A receptor currents. In vivo studies compared seizure activity in GAERS after intraperitoneal drug administration.
Results:   OXC potentiated GABA_A receptor current and aggravated seizures in GAERS, similarly to the effect of CBZ. Conversely, MHD showed only a minor potentiation of GABA_A receptor current and did not aggravate seizures.
Discussion:   A hydroxyl group at the C-10 position on the CBZ tricyclic structure in MHD reduces GABA_A receptor potentiation and seizure aggravation. Reports of the aggravation of absence seizures in patients taking OXC may result from circulating unmetabolized OXC rather than MHD.     

Clinical Monitoring During Carbamazepine Slow-Release, Once-Daily Monotherapy

Forty-eight patients with complex partial and/or tonic-clonic seizures were treated with an 8 p.m. single dose of carbamazepine slow release (CBZ-SR) monotherapy. The steady-state serum level profiles of carbamazepine (CBZ) and its metabolites CBZ-10,11-epoxide (CBZE) and 10,11-dihydro-CBZ-10,11-diole (CBZD) during 24 h in 21 of 48 patients treated with daily single doses of 8.4 (+/- 2.4) mg/kg body weight CBZ-SR were determined by a high-performance liquid chromatography procedure. The 8 a.m. CBZ levels correlated very well with the mean CBZ levels of the 24-h profile. Unlike CBZD, the individual 24-h mean CBZE levels also correlated well with the respective CBZ levels (CBZE = 14.2% +/- 2.9 of CBZ). Increasing CBZ-SR doses does not result in a proportional increase of CBZ levels. Clinical efficacy of changing from CBZ standard tablets under mono- or combination therapy or from therapy with other antiepileptic drugs to once-daily evening CBZ-SR monotherapy or commencement CBZ-SR therapy in previously untreated patients was monitored in 35 of 48 patients for a period of 8 months to 2 years. Complete seizure control was observed in 51% of patients and more than 75% reduction of seizure frequency in 14%. Eight of 11 previously untreated patients became seizure free. With change from CBZ monotherapy to CBZ-SR single-dose therapy, five of six patients became seizure free. Changing from other therapeutic regimens to CBZ-SR once-daily evening monotherapy was less successful.     

Effects of carbamazepine on prolactin secretion in normal subjects and in epileptic subjects

The effects of carbamazepine (CBZ) on spontaneous secretion of prolactin (PRL) and after stimulation with thyrotropin releasing hormone (TRH) were evaluated. Volunteer subjects after acute CBZ administration, and epileptic subjects with complex partial seizures chronically treated with CBZ, were examined. In an epileptic group, CBZ did not change TRH stimulatory effect on PRL secretion. No appreciable changes of PRL spontaneous secretion were observed, and only a small increase of sleep-entrained values with preservation of the normal secretory circadian rhythm was noted, both in normal subjects and in epileptic subjects. This result could be explained by a serotoninergic activity of PRL changes produced by CBZ in these various conditions agrees with the absence of published reports of CBZ side effects associated with hyperprolactinemia.     

Adjustment of Carbamazepine Dose to Offset the Effects of the Interaction with Remacemide Hydrochloride in a Double-Blind, Multicentre, Add-On Drug Trial (CR2237) in Refractory Epilepsy

Summary: Purpose: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer.
Methods: Patients taking CBZ entered a 4-week run-in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8-week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient.
Results: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced ≤50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L.
Conclusions: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add-on trials.     

Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep.

OBJECTIVE: To evaluate the cardiac autonomic effects of abrupt withdrawal of carbamazepine (CBZ) during sleep in patients with epilepsy. BACKGROUND: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncertain, with ictal or peri-ictal cardiorespiratory compromise appearing probable. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-to-beat heart rate variability (HRV) displays two main components: low frequency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. METHOD: Twelve patients with medically intractable seizures underwent abrupt withdrawal of CBZ to facilitate seizure recording during controlled circuit TV-EEG monitoring. Continuous EKG recording was begun 24 hours before CBZ reduction. Spectral analysis of the HRV was performed during selected samples of non-REM sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. RESULTS: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increased in 10 patients compared with a decrease in only one patient. CONCLUSION: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep as evidenced by increased LF/HF ratios. Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose to SUDEP.     

Computerized Analysis of EEG Background Activity in Epileptic Patients

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.     

Therapeutic drug monitoring of lamotrigine in patients suffering from resistant partial seizures

Sixty patients, all potential candidates for ongoing lamotrigine (LTG) treatment as add-on therapy for resistant partial seizures and receiving carbamazepine (CBZ) and/or valproate (VPA) treatment, were submitted to therapeutic drug monitoring (TDM). The aim was to evaluate the possible relation between serum levels and the clinical effect of LTG, to verify whether CNS toxicity has to be considered the result of a pharmacokinetic or a pharmacodynamic interaction with CBZ, and to investigate whether possible changes in the clinical response during long-term treatment are dependent on LTG serum level variations. Sixteen patients achieved complete control, 26 a >or=50% reduction in seizures, the remainder did not respond. Mean LTG serum concentrations were higher in responders than in nonresponders, the difference being statistically insignificant. The best results were observed in VPA-cotreated patients with the highest LTG blood levels. CNS toxicity occurred after giving LTG to subjects who subsequently developed the highest LTG concentrations, whereas CNS toxicity seemed unrelated to CBZ and CBZ-epoxide serum concentrations. No decrease in LTG, CBZ and VPA serum levels was observed even in patients showing a reduction in the response during long-term treatment.     

Outpatient sleep recording during antiepileptic drug monotherapy

The effects of sleep and sleep deprivation on epilepsy are well known, but the effects of seizures and antiepileptic drugs (AEDs) on sleep have been less well studied. We recorded nocturnal sleep in 17 patients receiving antiepileptic monotherapy with ambulatory cassette EEG devices. Twelve patients had complex partial seizures and five had tonic-clonic convulsions. Two patients' seizures were largely nocturnal, and no seizures occurred during sleep recording. Five patients each were taking phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), and two were taking clonazepam (CZP), all with therapeutic serum levels and no toxic symptoms. Total sleep time was reduced, wakefulness increased, and sleep latency prolonged in partial seizures as compared with generalized epilepsy. REM sleep was reduced and its latency decreased in partial seizure patients. Both groups had decreased slow wave sleep; that of partial seizure patients was decreased more markedly. PHT increased sleep latency and decreased sleep time, and CBZ increased awakening and diminished slow wave and REM sleep. Patients taking VPA had slight reduction in slow wave sleep; those taking CPZ had decreased sleep and REM latencies. Epilepsy may affect nocturnal sleep, and the effects of partial and generalized seizure disorders may be different. AEDs may also have differential effects on nighttime sleep. These may prove important in the long-term management of epileptic patients.     

Reduction of dosing frequency of carbamazepine with a slow-release preparation

The occurrence of side effects and epileptic seizures and the pharmacokinetics of carbamazepine (CBZ) and carbamazepine-10,11-epoxide were studied using a slow-release CBZ preparation, Neurotol slow, and a conventional CBZ preparation, Tegretol. The study was an open, randomized cross-over trial, with a 2 week study period for each preparation. Tegretol was given 3 times and Neurotol slow twice a day. The earlier CBZ dose was kept unchanged. The initial sample consisted of 24 adult epileptic patients receiving CBZ treatment of whom 20 patients were evaluable. The fluctuation in serum CBZ concentrations did not differ significantly between the 2 treatment periods, even though the interdose interval of Neurotol slow was 4 h longer than that of Tegretol. The switch-over from conventional CBZ to the slow-release formulation did not seem to alter the efficacy and side effects of CBZ. By using Neurotol slow instead of a conventional CBZ preparation, Tegretol, it is evidently possible to reduce the dosing frequency from 3 times a day to twice daily administrations.     

Monotherapy of lamotrigine versus carbamazepine in patients with poststroke seizure

OBJECTIVES: The incidence of seizures is known to be high in the elderly. The most common cause of an unprovoked seizure in the elderly population is stroke. These patients require effective and well-tolerated antiepileptic treatment because they frequently experience other medical conditions and use other medications that can interact with the antiepileptic treatment. The aim of the study was to analyze the tolerability and efficacy of lamotrigine (LTG) versus sustained-release carbamazepine (CBZ) treatment in newly diagnosed symptomatic poststroke seizure. METHODS: Sixty-four patients with a first post episode of seizures were randomized in a 1:1 ratio to either LTG or CBZ treatment and were followed up prospectively for up to 12 months for efficacy and tolerability of the drugs. RESULTS: More patients in the LTG group were seizure-free (72%) versus those in the CBZ group (44%; P = 0.06), but the numbers did not reach statistical significance because of a relative small number of study patients. The number of patients who withdraw from the study because of adverse events was statistically significantly less in the LTG group (3%) compared with the CBZ group (31%; P = 0.02). CONCLUSIONS: The LTG treatment in poststroke seizures versus CBZ treatment is a relatively better-tolerated drug and can be acceptable as initial treatment in this specific group of patients.