Loss of the initial efficacy of levetiracetam in patients with refractory epilepsy

PurposeThe efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures.MethodsWe enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period.ResultsA total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P = 0.054). Based on Kaplan–Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months.ConclusionThis study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.     

Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy

PURPOSE: To evaluate the long-term clinical usefulness of levetiracetam (LEV, Keppra((R))(1)) as add-on therapy in patients with refractory epilepsy. METHODS: Data for all 1422 patients with refractory epilepsy treated with LEV during the development program were analyzed for changes in seizure frequency per week, seizure freedom, and adverse events. RESULTS: Median percent reduction from baseline in seizure frequency per week over the whole treatment period was 39.6%, and no decrease over time was observed within each cohort exposed to LEV for durations ranging from 6 to 54 months. The median treatment period was 399 days (range 1-8 years). The proportion of responders during the first 3 months of LEV treatment was 39.2%. This proportion remained stable at 6 months (36.1%). Overall, 38.6 and 20.1% of patients had reductions in seizure frequency of at least 50 and 75%. Sixty-five (4.6%) patients were seizure-free over their entire treatment period, compared with 167 (11.7%) and 126 (8.9%) during their last 6 and 12 months of follow-up. Ninety-seven (19.8%) of 491 patients who received only one other antiepileptic drug (AED) in addition to LEV were seizure-free during their last 6 months. The proportion of patients who reduced their number of concomitant AEDs was 14.4% (205 patients), while 5.5% (79 patients) were treated with LEV only at the end of follow-up. Accidental injury (28.0%), infection (26.6%), headache (25.8%), somnolence (23%), asthenia (22.6%), and dizziness (18.9%) were among the most common adverse events. CONCLUSION: LEV offers sustained efficacy in patients with refractory partial seizures, and its long-term tolerability is similar to that seen in the short-term placebo-controlled trials.     

Levetiracetam bei generalisierten Epilepsien des Erwachsenenalters

Considering patients with generalized epileptogenesis and classical idiopathic generalized syndromes (IGE), levetiracetam (LEV) is only labeled for add-on treatment of juvenile myoclonic epilepsy (JME) in Germany. Although LEV is now off-patent, this labeling is unlikely to change; thus, LEV treatment in all other IGE and monotherapy of JME will fulfill the off-label therapy status. By means of an internet-based survey among the members of the German Society for Epileptology, the practical attitude concerning this problem was investigated. Furthermore, the actual status and treatment success in patients who are treated with LEV monotherapy were assessed by the authors. A total of 145 replies (17%) could be analyzed; 109 members (75%) declared treating patients with IGE with LEV in monotherapy, while 118 respondents (81%) treat patients with LEV in monotherapy as well as with add-on LEV beyond JME. Applying ??pseudo-placebo?? in order to maintain the labeling was refused by 84% (n?=?122) of respondents. In our investigation, 35 adults (27 females, 8 males, 18?C75 years, mean 31.5 years) currently being treated with LEV in monotherapy were identified; 29 patients have remained seizure-free for more than one year (83%). Neither from a clinical nor from a pharmacological perspective is it plausible that monotherapy or combinations with LEV should not be used in suitable patients with generalized epilepsy syndromes just because of the current labeling.     

Levetiracetam: an improvement of attention and of oral fluency in patients with partial epilepsy

PURPOSE: The aim of the present study is to verify whether patients with partial epilepsy receiving levetiracetam (LEV) as an add-on treatment show an improvement in cognitive function. METHODS: A neuropsychological battery of tests was administered to 35 patients with partial epilepsy before the assumption of LEV and after the achievement of the therapeutical dose of this drug, 7 weeks later. A control group of 35 patients with partial epilepsy was administered the same battery of tests twice, at the same time interval as the LEV group. The controls were administered the same pharmacological treatment, which did not include LEV in either of the two sessions. RESULTS: We found a statistically significant improvement in cognitive functioning, i.e. in attention and oral fluency, in patients receiving LEV compared to the controls. The responders to LEV were 28.6%. CONCLUSIONS: LEV as an add-on therapy improved attention level and verbal fluency in our sample of patients with partial epilepsy. It is reasonable to assume that LEV may influence the metabolism of attention and of language area, as already suggested for piracetam (PIR) from which LEV derives. Further studies are needed to confirm these findings.     

Levetiracetam in refractory epilepsy: a prospective observational study.

This prospective open-label study used flexible dosing schedules of levetiracetam (LEV) in patients with refractory epilepsy attending a single centre to explore its effectiveness in everyday clinical practice. One hundred and fifty-six patients with uncontrolled localisation-related or idiopathic-generalised epilepsy were prescribed adjunctive LEV following a 3-month baseline. The primary end points were seizure freedom for at least 6 months, > or = 50% reduction (responder) or <50% reduction for 6 months, or discontinuation of LEV due to lack of efficacy, adverse effects or both. Overall, 40 (26%) patients became seizure free on adjunctive LEV, including 8 (40%) with idiopathic-generalised epilepsy. Twenty-five (63%) of the seizure-free patients took 1000 mg LEV per day or less. A further 33 (21%) patients were classified as responders. LEV was withdrawn in 46 (29%) patients (27 adverse effects, 8 lack of efficacy, 11 both). Intolerable sedation, reported by 20 (13%) patients, was the commonest complaint leading to treatment failure. Behavioural side effects led to LEV withdrawal in 7 (5%) patients. LEV is an effective adjunctive treatment for refractory idiopathic and localisation-related epilepsies. Many patients who responded optimally to LEV did so at 1000 mg per day or less.     

Efficacy and safety of levetiracetam: an add-on trial in children with refractory epilepsy.

The aim of this multicentric, prospective and uncontrolled study was to evaluate the efficacy and safety of levetiracetam in 110 children with refractory epilepsy, of whom 21 were less than 4 years old. After a median follow-up period of 7 months, levetiracetam administration was effective (responders with >50% decrease in seizure frequency) in 39% of children, of whom 10 (9%) became seizure-free. The efficacy was higher in patients with localization-related epilepsy (58% of responders) than in those with generalized epilepsy (37% of responders). Levetiracetam was well tolerated. The main side effects of somnolence and irritability occurred in 14% of patients. In one patient acute choreoathetosis occurred after few doses of levetiracetam. Overall, the adverse effects were not severe. Children younger than 4 years were particularly tolerant. In conclusion, the present study confirms that levetiracetam is effective and well tolerated as an add-on treatment in children with refractory epilepsy. Our preliminary data also indicate that levetiracetam may be a valid therapeutic option for epilepsy in infants and young children.     

A prospective study of levetiracetam efficacy in epileptic syndromes with continuous spikes-waves during slow sleep

Purpose

To evaluate the add-on effect of levetiracetam (LEV) treatment on the EEG and clinical status of children with continuous spikes-waves during slow sleep (CSWS).

Methods

20 children with CSWS refractory to other conventional antiepileptic drugs (AEDs) received LEV 45–50 mg/kg/day as add-on treatment, and were prospectively followed for a minimum period of 18 months. The patient population comprised seven cryptogenic, seven symptomatic and six idiopathic cases (atypical benign partial epilepsy, aBECTs). The electrographic evaluation included 24 h EEG recordings taken every six months (minimum of three per child). Electrographically children were categorised as responders, partial responders or non-responders by comparing changes in the spike index (SI) during NREM-sleep with baseline SI before initiation of LEV. The clinical efficacy of LEV was assessed by comparing seizure frequency at the end of follow up with the baseline. The follow up duration varied from 18 to 53 months.

Results

Electrographic response was observed in 11 patients. Eight patients demonstrated a lasing response (more than 12 months): five from symptomatic, two – cryptogenic and one – idiopathic group respectively. Three children showed a partial response (6–12 months): one from symptomatic and two from idiopathic group.Eleven out of the 20 children were seizure free at baseline and during the whole follow up. The rest, six-symptomatic and three-cryptogenic patients, had seizures prior to LEV treatment initiation. Six became seizure free after add-on therapy with LEV, and in three children a significant reduction of seizure frequency was observed.

Conclusion

This study suggests that add-on therapy with LEV is more effective in children with CSWS resulting from a known underlying structural brain lesion (the symptomatic group).     

Topiramate treatment for nocturnal frontal lobe epilepsy

PURPOSE: Aim of this study was to evaluate the efficacy and tolerability of the antiepileptic drug topiramate (TPM) in a sample of patients with nocturnal frontal lobe epilepsy (NFLE). METHODS: A 24 patients with video-polysomnographically confirmed NFLE received topiramate as single or add-on therapy. They all completed diaries concerning the seizures frequency and complexity and underwent to periodic follow-up visits. We classified the patients as: seizure-free, responders or non-responders. RESULTS: 15 M; 9 F; mean age 29.3+/-10.4 years. The video-polysomnographic recordings showed a wide spectrum of seizures, ranging from repeated stereotypic brief motor attacks to prolonged attacks, with complex and bizarre behaviour; the recorded episodes occurred during non-REM sleep, both stage 2 and stage 3-4. The EEG during wakefulness was normal in all the patients, while seven of them showed epileptiform abnormalities during polysomnography. TPM was administered as single or add-on therapy from 50 to 300mg daily at bedtime. The follow-up duration ranged from 6 months to 6 years. The patients were classified as: seizure-free=6 (25%); responders (reduction of at least 50% of seizures)=15 (62.5%); non-responders=3 (12.5%). The adverse events were: weight loss (6 pts, 25%); paresthesias (3 pts, 12.5%); speech dysfunction (2 pts, 8.3%). All the adverse events disappeared within 3 months. CONCLUSIONS: In our experience, TPM seems to be effective in about 90% of patients with NFLE. Few of them experienced transitory adverse events. TPM could be included in the options for patients with this form of epilepsy.     

Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included a maximum 12-week down-titration period and 12 weeks of monotherapy at 1500 mg twice daily. In both phases, responder rate, seizure frequency, and adverse events were analyzed. RESULTS: A total of 286 patients (placebo, n = 105; LEV, n = 181) entered the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received LEV completed the entire study compared with only 10 of 105 patients (9.5%) in the placebo group (p = 0.029). The odds of completing the study on LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; p < 0.001). In the LEV monotherapy group, the median percent reduction in partial seizure frequency compared with baseline was 73.8% (p = 0.037), with a responder rate of 59.2%. Nine patients (18.4%) remained seizure-free on LEV monotherapy. CONCLUSIONS: Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.     

Levetiracetam in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center

OBJECTIVE: For the treatment of patients with chronic refractory epilepsies, development of new antiepileptic drugs is crucial. Three regulatory trials have demonstrated that add-on levetiracetam is efficacious in patients with localization-related epilepsy. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice. Therefore, more information is needed about the long-term profile of a new antiepileptic drug in clinical practice. METHOD: We analyzed all patients who had been treated with levetiracetam in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in early 2001 up to a final assessment point, at the end of 2003, using a medical information system. RESULTS: In total, 301 patients were included. One hundred thirty-eight patients (45.8%) discontinued LEV treatment during the 24-month follow-up period. Reasons for discontinuation were lack of efficacy in 15.9% of patients, adverse events in 6.0% of patients, and a combination of lack of efficacy and adverse events in 16.3% of patients. By Kaplan-Meier survival analysis, the continuation rate was 65.6% after 1 year and 45.8% after 2 years. About 15% of patients in this highly refractory group had a 3-month remission, whereas 10% of patients became seizure-free for longer periods. The most frequently reported side effects at the time of discontinuation were mood disorders, tiredness, and sleepiness. Variables predicting (dis)continuation of levetiracetam treatment could not be identified. CONCLUSION: Levetiracetam is a new antiepileptic drug that appears to be a useful add-on treatment in patients with refractory epilepsy. Its side effect profile is mild, with mood disorders being the most dominant adverse event.     

New observations in primary and secondary reading epilepsy: excellent response to levetiracetam and early spontaneous remission

The response of reading epilepsy to new antiepileptic drugs is not known. Due to the rarity of this condition little is known about its natural history. We evaluated and treated three patients with primary and secondary reading epilepsy. Seizures in all patients were characterized by twitching of the jaw or lips with secondarily generalized tonic-clonic seizures if reading continued. One patient with primary reading epilepsy became seizure-free with divalproex monotherapy and another with levetiracetam monotherapy after failure of lamotrigine. One other patient with secondary reading epilepsy became seizure-free with levetiracetam add-on therapy. The divalproex-treated patient stopped therapy less than 3 years after seizure onset and remained seizure-free with 6 years of follow-up. We propose levetiracetam as a first-line treatment for primary and secondary reading epilepsy. Spontaneous medication-free remission of primary reading epilepsy may occur within 3 years of seizure onset, much earlier than previously reported.     

Economic Evaluation of Add-on Levetiracetam for the Treatment of Refractory Partial Epilepsy in Korea

Objective

This study estimated the expected cost-effectiveness ratio expressed as the incremental cost per seizure-free day (SFD) gained and the incremental cost per quality adjusted life year (QALY) gained when using levetiracetam (LEV) as add-on therapy from a third-party payer perspective.

Methods

A 1-year dose-escalation decision-tree model comparing LEV plus standard therapy (ST) with ST alone was designed to combine transition probabilities, costs and outcomes. The short-term outcomes and probabilities were derived from a prospective, open-label clinical trial with 100 Korean adults with refractory partial epilepsy. All data for the direct medical costs were derived from Korean cost data extracted from reports published by the National Health Insurance Corporation.

Results

The average gain in SFDs attributed to LEV add-on was 18.3 days per patient per year and the incremental cost-effectiveness ratios (ICERs) for LEV add-on were US$ 44 per SFD per patient and US$ 11,084 per QALY gained. All sensitivity analyses showed that the model was robust to the assumptions made.

Conclusion

The economic evaluation indicates that, given a wide range of assumptions, the increased cost of treating patients having refractory partial epilepsy with LEV may be partially offset by a reduction in other direct medical costs. This reduction is a consequence of an increase in the number of SFDs and improved quality of life.     

Clinical predictors in patients with refractory epilepsy exposed to levetiracetam: a single-center study

Objectives –  This aim of the study was to ascertain the importance of clinical parameters on the response to treatment in refractory epilepsy patients on levetiracetam (LEV).
Materials and methods –  We retrospectively evaluated medical records of 132 patients aged 17–78 years with refractory epilepsy (defined as a failure of at least two antiepileptic drugs due to the lack of efficacy) exposed to LEV. We analyzed the response (seizure freedom or continuing LEV) using logistic regression.
Results –  Of 132 patients exposed to LEV, 103 cases continued the drug. Of the discontinuations (29/132), 75% were for lack of efficacy and 25% for tolerability problems. Twenty-three percent of the previously refractory patients achieved seizure freedom for at least 1 year with LEV in combination therapy. The dose of LEV in 80% of seizure-free patients was 1000 mg/day or less. The duration of epilepsy, age and sex were not associated with response to LEV. Seizure freedom was associated with epileptic syndrome or etiology. If no specific syndrome was recognized, there was a significantly greater chance for response compared with temporal lobe epilepsy (OR 20.76; 95% CI 2.12–203.61).
Conclusions –  Our study was based on the careful clinical evaluation of the patients with extensive use of video EEG (50%) and MRI scans (95%). These clinical predictors were evasive in previous studies. This study showed that they are worth pursuing but significantly larger groups of patients need to be investigated to reach significant findings.     

Seizure-free days observed in randomized placebo-controlled add-on trials with levetiracetam in partial epilepsy

PURPOSE: We examined the effect of adjunctive levetiracetam (LEV; 1,000 to 3,000 mg/day) on the number of seizure-free days gained per quarter in adult patients with refractory partial-onset epilepsy. METHODS: The treatment effect was studied in a meta-analysis using individual patient data of a subpopulation of patients (n = 846) emerging from the three randomized, double-blind, placebo-controlled, phase III trials (n = 904). RESULTS: Adding LEV effectively increased the number of days without seizures by 5.19 days per quarter [95% confidence interval (CI), 3.63-6.76; p = 0.0001; titration and stable dose periods]. CONCLUSIONS: LEV adjunctive treatment shows a clear benefit in terms of seizure-free days gained for patients with refractory epilepsy. This gain is significant for the pooled and for each LEV dose compared with placebo.     

Levetiracetam in patients with refractory epilepsy: results of the SKATE trial in Austria, Germany and Switzerland.

PURPOSE: To further evaluate the safety, efficacy and optimal dose of levetiracetam (LEV) in daily clinical practice among patients with uncontrolled partial epilepsy with or without secondary generalization. METHODS: In this phase IV, open-label, 16-week community-based study, 178 at least 16-year-old patients with refractory focal epilepsy were treated with 1000, 2000 or 3000 mg levetiracetam as adjunctive therapy. All patients started with 500 mg LEV b.i.d. (1000 mg/day); the dose was adjusted in 2-week intervals up to 1500 b.i.d. (3000 mg/day) depending on seizure control and tolerability. The main objectives were the adverse events, the percentage reduction in partial and total seizure frequency per week from baseline and the retention rate, defined as the percentage of patients taking LEV at the end of the 16-week treatment period. RESULTS: Of the 178 patients who took at least one dose of LEV 151 completed the study. Thus, the retention rate (number of patients taking LEV at the end of the 16-week treatment period) was 84.8%. Most frequently reported adverse events were asthenia, dizziness, headache, nausea, somnolence and hostility; the majority of these events were of mild to moderate intensity. The seizure-free rate of the ITT population with focal seizures was 16.7%, for all seizures 16.6%; the median reduction of focal seizure frequency was 47.6%, and 46.5% for all seizures. The 50% responder rate was 46.6% for focal seizures and 45.1% for all seizures. CONCLUSION: Add-on treatment with LEV in patients with refractory partial epilepsy was safe and effective in this study.     

Hypersomnia in an epilepsy patient treated with levetiracetam

We report a patient with focal epilepsy in whom increased sleep needs (hypersomnia) developed in the absence of subjective excessive daytime sleepiness (EDS) during an add-on treatment with levetiracetam (LEV).     

Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an open label study.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.     

Effects of levetiracetam on generalized discharges monitored with ambulatory EEG in epileptic patients

PURPOSE: Quantitative analysis of epileptiform discharges (EDs) before and after the initiation of an antiepileptic treatment is a useful tool to objectively documentate the efficacy of an antiepileptic drug (AED). Aim of this study was to evaluate the effect of levetiracetam (LEV) on EDs, monitored with ambulatory EEG (A/EEG), in a limited series of patients with generalized epilepsy. METHODS: We performed 24h A/EEG recording in basal condition and at follow-up after LEV therapy in 21 adult epileptic patients. Eleven received LEV as monotherapy and 10 as add-on. For each patient we quantified total epileptic activity considering the following parameters: total number, total duration, maximal duration and median duration of EDs. Self-reported information on the effect of LEV on clinical seizures was also collected, to determine the electro-clinical correlation. RESULTS: A high variability of the response to LEV was observed in the monotherapy group, without statistical differences for all the parameters investigated. A significant reduction of the total number of seizures (113.6 vs. 41.2; p=.01) was observed in patients in add-on therapy. The modifications of epileptiform EEG abnormalities did not necessarily correlate with the self-reported clinical impressions. DISCUSSION: The quantification of EDs monitored by A/EEG provides a useful objective support for evaluating the neurophysiologic profile and the real efficacy of an antiepileptic treatment. In our patients LEV was able to significantly reduce the EDs only in add-on therapy. Further larger studies are necessary to clarify the effects of LEV on electro-clinical features of generalized epilepsy.     

Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents

The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in juvenile myoclonic epilepsy (JME). The study group consisted of 32 patients with epilepsy (20 males, 12 females) with a mean age of 13 years 3 months (SD 7y 11mo) at seizure onset. LEV was administered as the first drug; all patients were followed up at 6 and 12 months. The dose that achieved seizure control ranged from 1000 to 2500mg/daily. At 6-month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12-month evaluation: 29 patients were seizure free; three patients were responders. No patients reported adverse events. These data provide preliminary evidence that LEV may be effective for treating patients with newly diagnosed JME.     

Efficacy and tolerability of levetiracetam in patients with therapy-resistant epilepsy and learning disabilities.

INTRODUCTION: The purpose was to evaluate the effects of levetiracetam (LEV) in routine therapy in learning disabled patients with therapy-resistant epilepsy. METHODS: In an open observational add-on study design, 46 patients (residents of the Bethel Epilepsy Centre) with severe therapy-resistant epilepsy and different degrees of learning disabilities, who were treated with LEV between its introduction in Autumn 2000 and February 2002, were evaluated retrospectively. Information on monthly seizure frequencies, seizure severity and psychiatric status was extracted from the current patient case records. A 3 months baseline and a 3 months LEV treatment period (after 3 months of titration) were compared. Responders were defined as having a 50% reduction in seizure frequency and being evaluated as good or very good in an ad hoc global clinical efficacy scale. When only one criterion was positive, a careful individual decision was made based on the impact on the patients' daily activities. RESULTS: The responder rate was 41.3% (34.8 for 50% seizure reduction). It was higher in focal and multifocal epilepsy as compared to symptomatic generalised epilepsy/Lennox Gastaut Syndrome (P<0.05). Antiepileptic response occurred in doses between 500 and 4000 mg/day. Changes in seizure severity were rare. Nine patients experienced positive psychotropic effects (mostly improved vigilance and mood); six of these patients had antiepileptic effects as well. Twelve patients had adverse effects, mostly mild; in three cases, however, more severe effects led to discontinuation. CONCLUSIONS: LEV is an effective and generally well-tolerated drug for this patient group, especially in focal and multifocal epilepsy.