Antiepileptic Drug Monotherapy Research Articles

Effects of new antiepileptic drugs on circulatory markers for vascular risk in patients with newly diagnosed epilepsy

Although it is well documented that long-term therapy with older antiepileptic drugs (AEDs) leads to an increase in risk for atherosclerosis, there has been only limited information regarding the vascular risk in patients who are treated with new AEDs. We therefore conducted a prospective longitudinal study to assess the potential effects of new AEDs on the circulatory markers for vascular risk in patients with newly diagnosed epilepsy. We recruited adult patients with epilepsy who began to receive monotherapy with one of the new AEDs, including levetiracetam (LEV), oxcarbazepine (OXC), and topiramate (TPM). Circulatory markers of vascular risk were measured twice before and after 6 months of AED monotherapy. A total of 109 patients completed the study (LEV, n = 40; OXC, n = 40; TPM, n = 29). Six months of monotherapy resulted in significant increases in low-density lipoprotein cholesterol (LEV, from 90.2 to 98.5 mg/dl, 9.2% increase, p = 0.025; OXC, from 96.5 to 103.2 mg/dl, 7.0% increase, p = 0.049), homocysteine (LEV, from 7.9 to 10.4 μm, 31.6% increase, p = 0.001; OXC, from 8.7 to 11.5 μm, 32.2% increase, p < 0.001; TPM, from 8.3 to 12.3 μm, 48.2% increase, p < 0.001), apolipoprotein B (LEV, from 63.6 to 77.4 mg/dl, 21.7% increase; OXC, from 67.0 to 83.2 mg/dl, 24.2% increase; TPM, from 66.7 to 84.4 mg/dl, 26.5% increase; all p < 0.001), and apolipoprotein B/apolipoprotein A1 ratio (LEV, from 0.51 to 0.61, 19.6% increase; OXC, from 0.52 to 0.67, 28.8% increase; TPM, from 0.50 to 0.67, 34.0% increase; all p < 0.001). Serum apolipoprotein A1 and folate were significantly decreased in TPM (from 139.1 to 132.1 mg/dl, 5.0% decrease, p = 0.014) and OXC (from 8.1 to 6.4 ng/ml, 21.0% decrease, p = 0.046) groups, respectively. There were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, lipoprotein(a), and vitamin B12 in all three groups. Our findings suggest that treatment with some new AEDs might be associated with alterations in circulatory markers of vascular risk, which could contribute to the acceleration of atherosclerosis and increased risk of vascular diseases.

Use of a Faxitron™ in longitudinal studies to assess rodent neonatal long bone development

This prospective, observational study assessed the development of preschool children aged 3–6 years, 11 months (n = 124) after in-utero anti-epileptic drug (AED) monotherapy exposure to valproic acid (VPA) (n = 30, mean age 52.00[±15.22] months) and lamotrigine (LT) (n = 42, mean age 50.12[±12.77] months), compared to non-exposed control children (n = 52, mean age 59.96[±14.51] months). As a combined group, AED-exposed children showed reduced non-verbal IQ scores, and lower scores on motor measures, sensory measures, and parent-report executive function, behavioral and attentional measures. When the VPA- and LT-exposed groups were analyzed separately, no cognitive differences were found, but control-VPA and control-LT differences emerged for most motor and sensory measures as well as control-VPA parent-report behavioral and attentional differences. No differences were noted between the VPA and LT groups. These findings suggest that VPA- and LT-exposed children should be monitored on a wider range of developmental measures than currently used, and at differing developmental stages.

Initial anticonvulsant monotherapy in routine care of children and adolescents: levetiracetam fails more frequently than valproate and oxcarbazepine due to a lack of effectiveness

Since anticonvulsants such as valproate or oxcarbazepine have quite a disadvantageous profile of possible adverse drug events (ADEs), safer alternatives are being sought. The newer anticonvulsant levetiracetam is often considered advantageous. We performed a chart review of children and adolescents aged from 0.5 to 16.9years, who had been started on an initial monotherapy with levetiracetam, valproate, or oxcarbazepine between 2007 and 2011, in order to analyze the therapy's failure rate during the first year. We differentiated failure of monotherapy due to a lack of effectiveness and due to ADEs. No psychometric tests were performed. Lack of effectiveness and inacceptable ADEs were assumed according to the judgment of physicians and families. Anticonvulsive monotherapy failed in 29/61 (48%) levetiracetam patients and in 18/49 (37%) valproate patients (for focal and generalized epilepsies; n.s.). This was caused by a lack of effectiveness in 25/61 (41%) levetiracetam patients and in 11/49 (22%) valproate patients (p ≤ 0.05). A modification of therapy due to ADEs was performed in 4/61 (7%) levetiracetam patients and in 7/49 (14%) valproate patients (n.s.). An anticonvulsive monotherapy failed in 21/42 (50%) patients treated with levetiracetam and in 10/34 (29%) patients treated with oxcarbazepine (for focal epilepsies; n.s.). Changes of monotherapy were caused by a lack of effectiveness in 17/42 (40%) of levetiracetam patients and in 6/34 (18%) of oxcarbazepine patients (p ≤ 0.05). ADEs leading to changes in therapy were reported for 4/42 (10%) of levetiracetam and 4/34 (12%) of oxcarbazepine patients (n.s.). An initial monotherapy of levetiracetam failed more frequently due to a lack of effectiveness than a monotherapy with valproate or oxcarbazepine. We found no significant difference in therapy failure due to ADEs.

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly

PurposeEpidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan. MethodsWe searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded. ResultsWe identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n=33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n=50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n=51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year. ConclusionThe most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

Developmental outcomes at preschool age after fetal exposure to valproic acid and lamotrigine: Cognitive, motor, sensory and behavioral function

This prospective, observational study assessed the development of preschool children aged 3–6 years, 11 months (n=124) after in-utero anti-epileptic drug (AED) monotherapy exposure to valproic acid (VPA) (n=30, mean age 52.00[±15.22] months) and lamotrigine (LT) (n=42, mean age 50.12[±12.77] months), compared to non-exposed control children (n=52, mean age 59.96[±14.51] months). As a combined group, AED-exposed children showed reduced non-verbal IQ scores, and lower scores on motor measures, sensory measures, and parent-report executive function, behavioral and attentional measures. When the VPA- and LT-exposed groups were analyzed separately, no cognitive differences were found, but control-VPA and control-LT differences emerged for most motor and sensory measures as well as control-VPA parent-report behavioral and attentional differences. No differences were noted between the VPA and LT groups. These findings suggest that VPA- and LT-exposed children should be monitored on a wider range of developmental measures than currently used, and at differing developmental stages.

Emergency room access for recurring seizures: when and why

To develop a hypothetical model identifying potentially modifiable predictive factors of Emergency Room (ER) visits by patients suffering from drug resistant epilepsy. During a 1-year period, all adult drug resistant patients followed by the same epileptologist were recruited after the occurrence of one or more epileptic attacks. They were divided into two groups based on whether they went to the ER after seizures. A prospective comparative analysis of the clinical and social characteristics of the two groups was performed in order to identify independent predictors of ER visits. Logistic regression analysis was used to confirm the potential predictive role of the evaluated variables. Logistic regression analysis confirmed the potential role in predicting ER visits for these variables: foreign nationality, current psychiatric therapy, current antiepileptic drug polytherapy, comorbidities, more than one episode in the same day and changes in usual seizure pattern. A relevant association was also found between the frequency of ER neuroimaging use and the following variables: occurrence of episodes on holidays or weekends, current antiepileptic drug monotherapy, multiple comorbidities and brain injury after seizure. The present study evaluated factors, some potentially amenable to change, related to drug resistant epileptic patients' ER visits following a seizure. This information may serve to improve the clinical and therapeutic management of patients, decrease the need for urgent care and reduce subsequent patient stress and related costs.

PND5 - Acute care utilization in patients with epilepsy on antiepileptic monotherapy

PND5 - Acute care utilization in patients with epilepsy on antiepileptic monotherapy

PND19 - Annual health care costs and utilization in adults taking long or short acting antiepileptic monotherapy

PND19 - Annual health care costs and utilization in adults taking long or short acting antiepileptic monotherapy

Fetal AED Exposure and Cognitive Outcome at Age 6

Investigators at Emory University, Atlanta, GA and multiple centers in the USA and UK conducted a prospective study of the effects of antiepileptic drug (AED) monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) on the intelligence quotient (IQ) at 6 years of age (age-6 IQ).

A systematic review of the evidence on the treatment of rapid cycling bipolar disorder

Rapid cycling is associated with longer illness duration and greater illness severity in bipolar disorder. The aim of the present study was to review the existing published randomized trials investigating the effect of treatment on patients with rapid cycling bipolar disorder. A MEDLINE search was conducted using combinations of the following key words: bipolar and rapid or rapid-cycling or rapid cycling and randomized. The search was conducted through July 16, 2011, and no conference proceedings were included. The search returned 206 papers and ultimately 25 papers were selected for review. Only six randomized, controlled trials specifically designed to study a rapid cycling population were found. Most data were derived from post hoc analyses of trials that had included rapid cyclers. The literature suggested that: (i) rapid cycling patients perform worse in the follow-up period; (ii) lithium and anticonvulsants have comparable efficacies; (iii) there is inconclusive evidence on the comparative acute or prophylactic efficacy of the combination of anticonvulsants versus anticonvulsant monotherapy; (iv) aripiprazole, olanzapine, and quetiapine are effective against acute bipolar episodes; (v) olanzapine and quetiapine appear to be equally effective to anticonvulsants during acute treatment; (vi) aripiprazole and olanzapine appear promising for the maintenance of response of rapid cyclers; and (vii) there might be an association between antidepressant use and the presence of rapid cycling. The literature examining the pharmacological treatment of rapid cycling is still sparse and therefore there is no clear consensus with respect to its optimal pharmacological management. Clinical trials specifically studying rapid cycling are needed in order to unravel the appropriate management of rapid cycling bipolar disorder.

Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study

Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866. We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivariate analysis of all children showed that age-6 IQ was lower after exposure to valproate (mean 97, 95% CI 94-101) than to carbamazepine (105, 102-108; p=0·0015), lamotrigine (108, 105-110; p=0·0003), or phenytoin (108, 104-112; p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=-0·56, p<0·0001), verbal ability (r=-0·40, p=0·0045), non-verbal ability (r=-0·42, p=0·0028), memory (r=-0·30, p=0·0434), and executive function (r=-0·42, p=0·0004), but other antiepileptic drugs were not. Age-6 IQ correlated with IQs at younger ages, and IQ improved with age for infants exposed to any antiepileptic drug. Compared with a normative sample (173 [93%] of 187 children), right-handedness was less frequent in children in our study overall (185 [86%] of 215; p=0·0404) and in the lamotrigine (59 [83%] of 71; p=0·0287) and valproate (38 [79%] of 40; p=0·0089) groups. Verbal abilities were worse than non-verbal abilities in children in our study overall and in the lamotrigine and valproate groups. Mean IQs were higher in children exposed to periconceptional folate (108, 95% CI 106-111) than they were in unexposed children (101, 98-104; p=0·0009). Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs non-verbal) abilities might be attributable to changes in cerebral lateralisation induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies.

Antiepileptic Drug Monotherapy Exposure and Suicide‐Related Behavior in Older Veterans

To examine the association between antiepileptic drug (AED) receipt and suicide-related behavior (SRB) in older veterans. Retrospective database analysis. Veterans Health Administration (VHA) inpatient and outpatient care. Veterans aged 65 and older in 2004 to 2006. SRB was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes, and new AED monotherapy was identified using the VHA product variable in pharmacy data. Comorbid conditions and medications were also identified as potential confounders using previously validated algorithms. Cox proportional hazards models controlling for the propensity to receive AEDs examined the association between any AED exposure, specific AEDs, and time to SRB. Within the eligible sample of 2.15 million individuals, 332 cases of SRB were found. Overall, 98% of participants were male, and 67% were non-Hispanic white. Affective disorders and severe psychiatric conditions were strongly associated with SRB and were included in the propensity score. AED exposure displayed a significant association with SRB (odds ratio = 4.10, 95% confidence interval (CI) = 3.85-6.63) after adjusting for propensity to receive AEDs. Stratified analyses found similar results for those with (hazard ratio (HR) = 4.00, 95% CI = 2.9-5.5) and without (HR = 4.57, 95% CI = 1.15-18.20) mental health comorbidities. Gabapentin, phenytoin, lamotrigine, levetiracetam, topiramate, and valproate were significantly associated with SRB. Exposure to five common AEDs was associated with SRB in older VHA beneficiaries. Given the strong associations between psychiatric comorbidity and SRB, clinicians treating elderly adults should weigh this potential adverse effect into their consideration for treatment of those receiving AEDs. Particular attention should be given to depression and suicidality screening in people prescribed AEDs.

Pregabalin monotherapy for epilepsy

Many people with epilepsy suffer from poorly controlled seizures, despite current antiepileptic treatments. Due to high rates of treatment resistance, there is interest in new pharmacological treatment options such as pregabalin. However, it remains unclear whether existing evidence of pregabalin is rigorous enough to support its monotherapy. To determine the efficacy and tolerability of pregabalin in people with epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7 ), MEDLINE (1946 to August week 1, 2012), EMBASE (1974 to August 2012) and the Chinese Biomedical Literature Database (CBM) (1978 to August 2012). No language restrictions were imposed. Randomised controlled trials (RCTs) comparing pregabalin with placebo or another antiepileptic drug monotherapy for epilepsy. Two review authors (QZ and LY) independently extracted trial data and assessed trial quality. We assessed the following outcomes: (1) time to withdrawal after randomisation; (2) time to achieve six-, 12- or 24-month remission; (3) the proportion of participants who remained seizure-free for six or more continuous months; (4) time to first seizure after randomisation; (5) validated quality of life measures; (6) health economic outcomes; (7) adverse effects. We expressed time-to-event outcomes as hazard ratios (HRs) with 95% confidence interval (CI), where an HR > 1 indicates an event is more likely to occur earlier on pregabalin than the comparator. Two short-term studies involving 753 participants met the inclusion criteria. Only one study investigated the effects of pregabalin compared with lamotrigine in patients with newly diagnosed partial seizures, and the other study investigated the effects of pregabalin compared with gabapentin in hospitalised patients with refractory partial epilepsy. There were no studies on generalised-onset tonic-clonic seizures (with or without other generalised seizure types).We found that pregabalin was inferior in comparison to lamotrigine when measuring time to withdrawal due to inadequate seizure control after dose stabilisation from randomisation: hazard ratio (HR) 4.52; 95% confidence interval (CI) 1.93 to 10.60; time to achieve six-month remission after dose stabilisation from randomisation: HR 0.56; 95% CI 0.41 to 0.76; the proportion of participants who remained seizure-free for six or more continuous months: RR 0.76, 95% CI 0.67 to 0.87 (Europe: 0.83, 95% CI 0.69 to 0.99; Asia: RR 0.70, 95% CI 0.57 to 0.86; the Americas: RR 0.62, 95% CI 0.33 to 1.19); and time to first seizure after dose stabilisation from randomisation: HR 1.74; 95% CI 1.26 to 2.39. There was no significant difference in safety-related outcomes between pregabalin and lamotrigine, but more participants in the pregabalin group developed somnolence, weight increase and convulsion. Pregabalin was better than gabapentin when measuring time to withdrawal due to all reasons after randomisation: HR 0.25; 95% CI 0.11 to 0.57; and time to withdrawal due to inadequate seizure control after randomisation: HR 0.41; 95% CI 0.18 to 0.92. No significant difference was found in safety-related outcomes between pregabalin and gabapentin. But we found some limitations in the study design which may have had an influence on the results. Pregabalin seems to have similar tolerability but inferior efficacy in comparison to lamotrigine for newly diagnosed partial seizures. However, considering the limitations in the study design (such as the short-term follow-up and the low initial target dose selection), the results should be interpreted with caution. The available data were too limited to draw any conclusions between pregabalin and gabapentin. The result indicated that the treatment effects were influenced by the study regions. The clinical disadvantage of pregabalin was more prominent in Asia when compared with lamotrigine. We should determine whether pregabalin has ethnic differences in the treatment of epilepsy in the future. This review does not inform any treatment policy for patients with generalized onset tonic-clonic seizures. Further long-term trials are needed to investigate the genuine effectiveness of pregabalin as monotherapy.

Early‐onset absence epilepsy: SLC2A1 gene analysis and treatment evolution

To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

Seizure recurrence and remission after switching antiepileptic drugs

Studies of seizure outcome in patients undergoing serial antiepileptic drug trials have all been uncontrolled, with no account made for the spontaneous changes in disease state that could confound the elucidation of drug effects. In addition, no study has ever looked at outcome following antiepileptic drug switch in seizure-free patients, despite the fact that this is done routinely in clinical practice. We aimed to address both of these issues using a matched case-cohort design. We followed patients taking phenytoin or carbamazepine in monotherapy for focal epilepsy who were being crossed over to a newer agent as part of studies on the metabolic effects of anticonvulsant therapy. Many had been seizure-free but were being switched nonetheless due to side effects or concerns about long-term adverse consequences. Each patient was matched with two controls of the same seizure status who were taking anticonvulsant monotherapy and whose drug was not switched. Seizure freedom over the ensuing 6 months was the primary end point. There were 43 cases and 86 matched controls. Twenty-three patients (cases) had been seizure-free on their old drug; 5 (21.7%) had seizure recurrence after drug switch compared to 2 (4.3%) of 46 matched controls. Twenty patients (cases) were having seizures on their old drug; 6 (30%) entered remission after drug switch, compared to 8 of 40 matched controls (20%). The two groups differed at baseline in number of anticonvulsants previously failed, which was the most important factor for prognosis. After statistical adjustment to account for this, seizure-free patients had 6.53 times higher odds of seizure recurrence if switched to a new drug (95% confidence interval [CI] 1.02-61.19; p = 0.06). Non-seizure-free patients had 1.66 times higher odds of remission if they remained on the same drug compared to switching, although this was not significant (95% CI 0.36-8.42; p = 0.532). Neither dose changes, nor drug mechanism, nor duration of seizure freedom had any bearing upon the results. Although the large majority of seizure-free patients remain so when switched to another agent, about one sixth have a recurrence attributable to the change. Conversely, our study design provides the first evidence to suggest that most improvements in drug-resistant patients are likely due to spontaneous remissions, not new drug introductions. These findings have conflicting implications for two competing models of comparative antiepileptic drug efficacy, which will require further study to elaborate.

Utilization patterns of antiepileptic drugs among adult epileptic patients at a tertiary hospital in Oman

To describe utilization patterns of antiepileptic drugs (AEDs) among adult epileptic patients at a tertiary hospital in Oman. Data were collected retrospectively from January 2006 to December 2009. The study included all adult (>18 years) epileptic patients on AEDs and followed up at a neurology clinic at Sultan Qaboos University Hospital in Oman. All reported therapeutic drug monitoring (TDM) requests for serum AED concentrations were also collected. Institutional ethical approval was sought and obtained. The study included a total of 372 patients with a mean age of 34 ± 15 years. Monotherapy AEDs accounted for 53% of the prescriptions, whereas polytherapy with two or three AED combinations accounted for 27% and 20% respectively. The most frequently prescribed AED was sodium valproate (27%) followed by carbamazepine (23%). The commonly prescribed AED combinations were sodium valproate with clonazepam (12%) followed by sodium valproate with lamotrigine (12%). Evaluation of 574 TDM requests for three AEDs showed that 57% of carbamazepine, 78% of phenytoin and 54% of valproic acid requests were either above or below the recommended therapeutic threshold. Most of these requests were ordered from the hospital's emergency department for suspected insufficient serum concentrations. Antiepileptic drug monotherapy is still the most frequently employed therapeutic strategy in adult patients with epilepsy in keeping with the standard therapeutic guidelines. Sodium valproate is commonly used for different types of seizures reflecting its wide spectrum of anticonvulsant potential. Newer AED utilizations are becoming increasingly popular in our subjects particularly as add-on with other standard AEDs.

Le syndrome of transient epileptic amnesia et l’epileptic amnesic syndrome sont-ils une même entité ?

A chronic subjective cognitive impairment can be symptomatic of temporal lobe epilepsy (TLE); it is thereby frequently reversible with the use of antiepileptic monotherapy. In this field, two distinct syndromes have been described: the Epileptic Amnesic Syndrome (EAS) and the Syndrome of Transient Epileptic Amnesia. Their diagnostic criteria have much in common but identification of STEA is based only on transient amnesic attacks. On the contrary, EAS takes into account subtle temporal lobe seizures. Here, we report a case where chronic cognitive disturbances were combined with very limited temporal lobe seizures while amnesic attacks were lacking. Antiepileptic drug treatment led to normalization of cognitive function. The criteria of STEA were not applicable because of the lack of transient amnesia in the patients’ medical history. Considering brief episodes of flashbacks and abdominal pain as possibly seizure-related, the criteria of EAS were more operative: they allowed proper investigation to confirm TLE in our patient.

Trends in antiepileptic drug utilisation in UK primary care 1993–2008: Cohort study using the General Practice Research Database

PurposeTo describe changes in utilisation of antiepileptic drugs (AED) by people with epilepsy in the United Kingdom during 1993–2008. MethodsCohort study of 63,586 participants with epilepsy and prescribed AEDs from 434 UK family practices. Prescriptions for different AEDs and AED combinations were evaluated by calendar year, gender and age group. ResultsTotal follow-up was 361,207 person-years, with 282,080 person-years treated with AEDs and 79,126 person-years untreated. AED monotherapy accounted for 72.6% of treated person years of follow-up. Carbamazepine and valproates were among the most commonly used medications throughout 1993–2008. Phenytoin accounted for 39.5% of treated person-years in 1993 declining to 18.3% by 2008. Use of barbiturates declined from 14.3% in 1993 to 6.0% in 2008. In contrast between 1993 and 2008 there were substantial increases in the use of lamotrigine (2.0% to 17.0%) and to a lesser extent levetiracetam (0% to 8.6%). Newer AEDs were more frequently prescribed to younger participants, especially women aged 15–44 years, while older adults were more likely to be prescribed longer established AEDs. In 1993, 201 different AED combinations were prescribed, increasing to 500 different combinations in 2008. Combinations of sodium valproate and carbamazepine were frequent throughout, while sodium valproate and lamotrigine was frequent in 2008. ConclusionsUtilisation of newer AEDs in UK primary care has increased between 1993 and 2008 with increasing use of diverse combinations of AEDs. The data quantify exposure to AEDs relevant to planning analytical pharmaco-epidemiological studies, as well as providing information to inform prescribing policies.

Comparative safety of antiepileptic drugs during pregnancy

To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy. The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months' gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression. The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0-8.5) for valproate, 2.9 (1.4-5.8) for phenobarbital, and 2.2 (1.2-4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip. AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population.

Prevalence, utilization, and costs of antiepileptic drugs for epilepsy in Germany—a nationwide population-based study in children and adults

Nationwide analyses of drug use can provide a prevalence estimate of the underlying disease and can help in understanding the characteristics of treatment. This study aimed for such analyses regarding the utilization of antiepileptic drugs (AED) for epilepsy in Germany. In 2009, all 4,115,705 AED prescriptions of all German patients with statutory health insurance (70,011,508 persons) were retrospectively analyzed. The IMS(®) LRx database served as data source, which accesses nationwide pharmacy data centers processing all German prescription data. To establish the age and sex-specific percentage of patients taking AED because of epilepsy, we used a second database, Disease Analyzer(®), which covered a representative sample of the German population (7.2 million patients) and contained ICD10 codes alongside with prescription data. The period prevalence of patients taking AED because of epilepsy was 9.1/1,000 (children/adolescents: 5.2/1,000; elderly: 12.5/1,000). Of the patients, 83.1 % took at least one of four AED: valproate (29.8 %), carbamazepine (26.4 %), lamotrigine (21.4 %), and levetiracetam (16.9 %). Oxcarbazepine and sultiame were popular with pediatricians. Elderly patients frequently received phenytoin and primidone. More than half of the patients were treated by family physicians; 68 % took AED in monotherapy and 7.9 % received >2 AED (children/adolescents: 12.5 %). The costs for AED prescribed for epilepsy amounted to €285.1 Mio (median AED costs/patient: €158/a). The German 2009 prevalence of epileptic patients taking AED was 9.1/1,000. Family physicians cared for the majority of patients. Prevalence and prescribing patterns changed with age. Costs of AED against epilepsy added up to 1 % of total medication costs in Germany.