Older Antiepileptic Drugs Research Articles

Trends in the use of antiepileptic drugs in Taiwan from 2003 to 2007: A Population-Based National Health Insurance study

The aim of this study was to evaluate the prevalence of prescription and use of antiepileptic drugs (AEDs) for the treatment of epilepsy and other indications in a nationwide population using a prescription database. AED prescription data were collected from the National Health Insurance Research Database (NHIRD) in Taiwan for a 5-year period (2003-2007). Patients prescribed AEDs at least two times from 2003 to 2007 were selected for the study from a random sample that included approximately 600,000 people. The prevalence of AED use (per 1000 inhabitants) increased from 12.6 in 2003 to 13.8 in 2007. The prevalence of newer AED use increased progressively from 1.0 in 2003 to 3.8 in 2007, but the prevalence of older AED use decreased during this time (11.6-10). Carbamazepine and valproic acid were the most common AEDs used. Among the newer generation of AEDs, gabapentin was the most frequently used. Newer AEDs were used primarily to treat pain disorders. The primary class of drugs used to treat epileptic disorders was older AEDs. An increase in the use of AEDs was observed over a 5-year period in data collected from NHIRD. This might implicate the use of newer compounds at clinical practice not only increased in the treatment of epilepsy, but also in the conditions other than epilepsy especially pain disorders.

Seizure Management in the Setting of Hepatic Disease

In the past 20years, many antiepileptic drugs (AEDs) have been marketed that are not significantly metabolized by the liver, but some patients still require the use of older and more metabolically complex AEDs for optimal seizure control, and current economic and insurance-coverage limitations have forced many patients to switch to less expensive agents, which are often the older AEDs. For the patient with hepatic disease, it is clearly preferable to use medications with little potential to exacerbate their condition. In my practice, I try to use agents with simpler metabolism, especially for patients with multiple medical problems. Doing this can mean using AEDs in monotherapy that are FDA-approved only for adjunctive use. I also find that older agents and hepatically metabolized AEDs can be the most appropriate for particular patients. Selection of the optimal seizure medication requires consideration of multiple factors, only one of which is the impact on liver function. I routinely obtain an executive laboratory panel at least yearly for even the healthiest of patients, to reassure both the patient and myself that the metabolism of their AED regimen is not significantly affected. Occasionally, a change or abnormality in liver function is identified. Certainly hepatic disease can make epilepsy management more difficult, and communication between the neurologist and the other treating physicians is a necessity, although the neurologist and the hepatologist may have differing opinions on how to respond to worsening liver function. Concern about potential liver damage by AEDs may prompt unnecessary discontinuation, sometimes with disastrous consequences for seizure control. Overly complex AED regimens can cause underlying liver problems to worsen. Clinical observation and judgment must complement the data derived from laboratory parameters. Worsening hepatic disease can also result in encephalopathic states that worsen or mimic seizures. The EEG can often be helpful in differentiating these conditions and is crucial in determining appropriate epilepsy therapy.

Migraine Prophylaxis With Topiramate and Bone Health in Women

Antiepileptic drugs (AEDs) are commonly used for prevention of migraine headaches. Bone loss is a known complication, particularly associated with use of older AEDs. Topiramate is a newer AED, widely used for migraine prevention, but no evidence is currently available on its effect on bone metabolism. In a clinic-based pilot study, we evaluated bone health by examining biochemical and radiological markers of bone metabolism, in women with migraine. Osteopenia was noted in 53% of the patients and was associated with the duration of exposure to topiramate (P = .04).

Self-reported symptoms in patients on antiepileptic drugs in monotherapy

To ascertain the frequency of self-reported symptoms in patients taking antiepileptic drugs (AED). We included patients on carbamazepine (CBZ) n = 36, valproate (VPA) n = 21, levetiracetam (LEV) n = 12, phenytoin (PHT) n = 11, lamotrigine (LTG) n = 20, patients not taking anticonvulsive drugs n = 19, and healthy control subjects (CTRL) n = 41 to complete the Liverpool Adverse Event Profile (LAEP). The mean LAEP scores were CBZ/PHT/LEV/VPA/LTG/noAED/CTRL = 44.97/42.00/41.00/40.33/32.42/42.00/30.80. LEV scored overall in the same range as the older AED but had a different adverse effect profile with self-reported anger (33%) and shaky hands (42%) particularly frequent. Patients with depression or uncontrolled epilepsy had significantly higher LAEP scores than patients without depression or uncontrolled epilepsy. Our unblinded observational study of self-reported symptoms suggested LTG was overall the drug with the least self-reported symptoms. Larger studies are needed to determine whether this was a truly significant difference. LEV had a different side effect profile to older AED. Confounding factors were depression and uncontrolled epilepsy. This observation should be further tested with randomized studies.

Pharmacotherapy for children and adolescents with epilepsy

Introduction: Childhood epilepsies are the most frequent neurological problems that occur in children. Despite the introduction of new antiepileptic drugs (AEDs) 25 – 30% of children with epilepsy remain refractory to medical therapy.Areas covered: This review aims to highlight the main published data on the treatment of childhood epilepsy. The electronic database, PubMed, and abstract proceedings were used to identify studies. The aim of antiepileptic therapy should be to provide complete seizure control, if possible without the burden of any side effect. Since 1993, new agents have been approved for use as an antiepileptic. Although there are few published data (especially in pediatric populations) to establish that the second-generation AEDs are more efficacious than the older AEDs, they appear to have better tolerability.Expert opinion: Old AEDs are efficacious agents that continue to play a major role in the current treatment of epilepsy. These agents actually remain the first-line treatment for many specific seizure types or epileptic syndromes. The new AEDs were initially approved as adjunct agents and – subsequently – as monotherapy for various seizure types in the adult and children. Despite these improvements, few AEDs are now considered to be a first-choice for the treatment of epilspsy in children.

Contemporary management of migrainous disorders in pregnancy

Migraine is a frequent event among women of reproductive age. It is difficult to predict the course and severity of disease that migraineurs will endure during pregnancy. Treatment is often compromised during pregnancy because of concerns regarding pharmacotherapy and fetal well being. The majority of women with migraine during pregnancy will not require ongoing pharmacotherapy or prophylaxis. Nonpharmacologic strategies should be the first-line treatment of migraines. For severe migraines, recent cohort studies documenting the use of triptans for treatment during pregnancy have shown no increase in adverse pregnancy and fetal outcomes above the average rate. High-dose valproate is the only antiepileptic drug available for migraine prophylaxis that has been shown to cause long-term cognitive effects in infants exposed during gestation. Congenital syndromes have been described for most of the older antiepileptic drugs but less so for many of the newer drugs. These newer medications appear to have improved safety profiles for use in pregnancy but there is still information lacking from larger patient cohorts and longitudinal studies of neurodevelopmental outcomes. There is also evidence to support use of beta-blockers and calcium-channel blockers for migraine prevention during pregnancy. For those patients who develop debilitating migraine or whose migraines interfere with activities of daily living, there are several options for treatment and headache prevention that have a low likelihood of compromising fetal well being.

18. KONQUEST: Keppra versus older AEDS and neuropsychiatric, neurocognitive and quality of life outcomes in treatment of epilepsy as substitution monotherapy

Objective: To compare a broad range of epileptic and psychological outcome measures in patients who had substitution monotherapy with levetiracetam (LEV) versus one of two older anti-epileptic drugs (AEDs), carbamazepine (CBZ) or valproate (VPA).

Non-interventional surveillance study of adverse events in patients with epilepsy

Compare adverse events (AEs) in patients with epilepsy taking different antiepileptic drugs (AEDs) using standardized physician-completed questionnaires. Multicenter, observational, cross-sectional study in epilepsy patients aged ≥4 , stable on 1-2 AED(s) for ≥3 months. One thousand and nineteen patients were evaluated: 28.7% took newer, 71.3% older (or older + newer) AED(s); 56.9% monotherapy; 43.1% polytherapy. Overall, 68.3% reported ≥1 AE (61.3% newer; 71.1% older AEDs), most commonly: cognitive function disturbances, sedation, psychological problems. Patients taking newer AEDs were significantly less likely to report ≥1 AE (OR [95% CI]: 0.64 [0.46-0.89], P = 0.008). Treatment/dose changed at study visit: 22.8% (17.5% newer; 24.9% older AEDs) because of (newer/older); lack of efficacy (6.2%/7.8%); AEs (4.1/8.4%); absence of seizures (3.8/4.0%). Patients receiving levetiracetam or lamotrigine were significantly less likely to report AEs/modify treatment. Patients taking newer AEDs were significantly less likely to report AEs, although the non-randomized study design does not allow the lower rate of AEs to be attributed with certainty to the use of newer AEDs. A standardized AE questionnaire appeared useful for monitoring AEs/optimizing AED therapy.

Prescribing pattern of anti‐epileptic drugs in an Italian setting of elderly outpatients: a population‐based study during 2004–07

The aims of the study were to assess the trend of older and newer anti-epileptic drugs (AEDs) in the elderly population and to analyze the effects of a health-policy intervention with regard to AED use in general practice in a setting in Southern Italy. Data were extracted from the 'Caserta-1' Local-Health-Unit Arianna database in the years 2004-07. Patients aged over 65 years, receiving at least one AED prescription and registered in the lists of 88 general practitioners, were selected. The use of older and newer AEDs was calculated as 1 year prevalence and incidence of use and defined daily dose (DDD) per 1000 inhabitants day(-1) . Sub-analyses by gender, age and indication of use were performed. Most of AED users were treated because of neuropathic pain (64.8%). However, the main indication of use for older AEDs (57.8%) was epilepsy, whereas newer AEDs (79.5%) were used for neuropathic pain. Prevalence and incidence of newer AED use increased until 2006, followed by a reduction in 2007. Newer AEDs, particularly gabapentin and pregabalin, were used in the treatment of more patients than older AEDs. However phenobarbital, accounting for more than 50% of total AED volume, was the most prescribed medication during the entire study period. An increasing use of AEDs has been observed during 2004-07, mostly due to the prescription of newer compounds for neuropathic pain. The fall in the use of newer AEDs during 2007 coincides with revised re-imbursement criteria for gabapentin and pregabalin. The large use of phenobarbital in the elderly should be considered in the light of a risk of adverse drug reactions.

Antiepileptic Drug Interactions - Principles and Clinical Implications

Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to drug interactions. The purpose of the present review is to focus upon clinically relevant interactions where AEDs are involved and especially on pharmacokinetic interactions. The older AEDs are susceptible to cause induction (carbamazepine, phenobarbital, phenytoin, primidone) or inhibition (valproic acid), resulting in a decrease or increase, respectively, in the serum concentration of other AEDs, as well as other drug classes (anticoagulants, oral contraceptives, antidepressants, antipsychotics, antimicrobal drugs, antineoplastic drugs, and immunosupressants). Conversely, the serum concentrations of AEDs may be increased by enzyme inhibitors among antidepressants and antipsychotics, antimicrobal drugs (as macrolides or isoniazid) and decreased by other mechanisms as induction, reduced absorption or excretion (as oral contraceptives, cimetidine, probenicid and antacides). Pharmacokinetic interactions involving newer AEDs include the enzyme inhibitors felbamate, rufinamide, and stiripentol and the inducers oxcarbazepine and topiramate. Lamotrigine is affected by these drugs, older AEDs and other drug classes as oral contraceptives. Individual AED interactions may be divided into three levels depending on the clinical consequences of alterations in serum concentrations. This approach may point to interactions of specific importance, although it should be implemented with caution, as it is not meant to oversimplify fact matters. Level 1 involves serious clinical consequences, and the combination should be avoided. Level 2 usually implies cautiousness and possible dosage adjustments, as the combination may not be possible to avoid. Level 3 refers to interactions where dosage adjustments are usually not necessary. Updated knowledge regarding drug interactions is important to predict the potential for harmful or lacking effects involving AEDs.

Pregnancy and epilepsy management and outcome: an update

Epilepsy affects one in 100 individuals. Although epilepsy is gender neutral, women face more challenges with regard to treatment than men. Treatment of women with epilepsy is a therapeutic challenge since they are unlikely to be medication free. An estimated 1 million women with epilepsy are of childbearing age. Each year, approximately 20,000 births occur in women with epilepsy. Despite these challenges, over 90% of women with epilepsy have normal healthy outcomes. Ensuring seizure control is of utmost importance to the health of the mother and fetus. Serum concentrations of antiepileptic drug (AED) decrease during pregnancy resulting in an increased risk of seizure activity, which may result in serious consequences such as maternal injury or fetal and/or maternal demise. Teratogenicity secondary to AED drug exposure has long been reported, especially with the older AEDs, and to some degree with newer agents. More recently, the discovery of long-term cognitive impairment has been reported in offspring exposed to valproate in utero. Choice of AED must balance seizure control with minimizing the risk of malformations and other health issues. Prenatal planning is warranted whenever possible in order to address these concerns. Supplementation with folic acid pregestationally may be helpful in preventing malformations such as spina bifida.

Metabolic consequences of antiepileptic drugs

Chemical properties of the widely used older generation antiepileptic drugs (AEDs) suggest that they might be responsible for a number of medical comorbidities. AEDs which induce the cytochrome P450 system adversely affect bone, lipid, and gonadal steroid metabolism. Specifically, phenytoin causes loss of bone mass in women, and both phenytoin and carbamazepine produce increases in serum lipids and C-reactive protein, as well as decreases in bioactive testosterone in men. Patients treated with inducing AEDs are at increased risk of fracture. Some contradictory data raise the question of whether bone mass is truly related to enzyme induction, and analogously, of whether reductions in testosterone truly account for male sexual dysfunction. Data showing elevations of surrogate cardiovascular and cerebrovascular risk endpoints with epilepsy patients, mostly inducing AED treated, are consistent and concerning, however. Another older AED, valproate, is associated with the occurrence of polycystic ovary syndrome when used in young adulthood or adolescence. Older generation AEDs are associated with a panoply of metabolic abnormalities. Although more research is needed to see whether individual drugs are directly tied to specific clinical outcomes (e.g. risk of infarction), extant data are sufficiently concerning to suggest that these drugs may produce significant adverse health consequences. Newer generation AEDs may be preferable.

Vigabatrin (VGB) administered during late gestation lowers maternal folate concentration and causes pregnancy loss, fetal growth restriction and skeletal hypoplasia in the mouse

Vigabatrin (VGB) has several therapeutic advantages over older antiepileptic drugs (AED), but there is a lack of information about its potential reproductive toxicologic effects. Our aim was to evaluate the consequences of VGB administered during late gestation on fetal growth and development in the mouse. Based on the results of our previous study, we administered groups of mice a single dose of 450 mg/kg VGB on one of gestation days (GD) 15, 16 or 17. Fetuses were collected on GD 18. VGB groups had a significant incidence of fetal death, abortion, intrauterine growth restriction (IUGR), and hypoplasia of the axial skeleton, metacarpals, metatarsal and phalanges. Abortion was characterized by visible hemorrhagic expulsion of the embryos with their membranes. Maternal plasma folate (FA) and vitamin B12 concentrations were found to be markedly reduced within 12 h of VGB treatment. Mice were supplemented with FA from GD 12 through GD 17 with or without a single dose of VGB on GD 15. This group had no abortions. Their fetuses had better body weight and lower frequency of IUGR than those of the non-supplemented VGB group. These data suggest that reductions in maternal FA and vitamin B12 concentrations play an important role in fetal loss, IUGR and skeletal hypoplasia induced by VGB during late gestation in the mouse. In view of the finding that a significant maternal toxicity is associated with this dose regimen, additional groups of mice were treated with 350 mg/kg VGB during embryogenesis and late gestation. This treatment was found to be maternally nontoxic. However, this low dose also resulted in significant fetal loss and IUGR when treatment occurred during late gestation. These data support the hypothesis that late gestation is particularly susceptible to VGB-induced fetal loss and IUGR in the mouse.

The Cost Effectiveness of Rufinamide in the Treatment of Lennox-Gastaut Syndrome in the UK

Lennox-Gastaut syndrome (LGS) is a catastrophic childhood form of epilepsy. The syndrome is characterized by mental impairment, frequent seizures of multiple types that are particularly resistant to treatment, and high rates of seizure-related injury. With the introduction of newer, but more costly, antiepileptic drugs (AEDs), it is important that decision makers are able to assess their value in the management of this rare and difficult-to-treat condition. To evaluate the cost effectiveness, from the UK NHS perspective, of rufinamide in patients with LGS. An individual patient-simulation model was developed to estimate the total treatment-related costs and clinical benefits of rufinamide compared with topiramate and lamotrigine over a 3-year time horizon. The model examines the treatment scenarios of adding rufinamide, lamotrigine or topiramate to older AEDs (standard therapy), or standard therapy alone within a primary-care or community setting. Three placebo-controlled clinical trials of adjunctive AED treatment for children with LGS were analysed. There are no head-to-head comparator studies. Between 98 and 139 patients were randomized in each study and the mean age in each study was 10, 11 and 14 years. A mixed-treatment comparison using a random-effects model was carried out on the number of patients in each response category, using the placebo arms of the respective trials. The primary outcome measure was the percentage of successfully treated patients, defined as >50% reduction in the frequency of total seizures and drop attacks. The hypothesis being tested was formulated after data collection. Costs ( pound, year 2006/07 values) of patient monitoring, switching treatments, hospitalization due to seizure, treatment of adverse effects, and personal and social services were included in the analysis. Results of 10,000 Monte Carlo simulations were bootstrapped to conduct probabilistic sensitivity analysis. Over 3 years, adjunctive rufinamide resulted in higher total costs than topiramate and lamotrigine; however, with more patients being treated successfully, this leads to acceptable incremental cost-effectiveness ratios. If society is prepared to pay at least 250 pounds for a 1% increase in the number of successfully treated LGS patients, in terms of a 50% reduction in the frequency of drop attacks, the probability of the treatment with rufinamide being cost effective is >80%. This cost-effectiveness analysis suggests that rufinamide results in more LGS patients being treated successfully at a reasonable cost from a UK NHS perspective.

Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs

Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm]. Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

Do New Antiepileptic Drugs with Novel Mechanisms of Action Suggest Reconsideration of Rational Polypharmacy?

Although effective control of epilepsy can be achieved by a single antiepileptic drug (AED), the condition persists in a significant number of patients despite increasing dosages with monotherapy and polytherapy. Treatment with combinations of older AEDs has been known to cause undesirable drug–drug interactions and side effects. However, there has been renewed interest in polytherapy with the advent of newer AEDs with novel mechanisms of actions that are less likely to cause adverse effects in patients. Animal seizure models are useful for determining whether AEDs will be effective in generalised or partial seizures prior to clinical studies and isobolgraphic analysis may allow for a more systematic, rational approach to predicting whether a given combination of drugs will result in a greater or lesser pharmacologic effect. Since one treatment strategy does not suit all patients, studies should focus on the tolerability and safety of specific combinations of AEDs in order to provide guidance to physicians. In summary, pharmacokinetic interactions must be taken into account in studies in humans and animals with measurement of toxicity as well as efficacy.

Introduction—Annual Course 2008: American Epilepsy Society

Introduction—Annual Course 2008: American Epilepsy Society

End-of-dose emergent psychopathology in ambulatory patients with epilepsy on stable-dose lamotrigine monotherapy: A case series of six patients

Objective Specific psychological withdrawal symptoms following the cessation of treatment with many drugs that affect the central nervous system, including anxiolytics and antidepressants, have been well documented. Studies have investigated withdrawal symptoms associated with some of the older antiepileptic drugs, but the potential for withdrawal symptoms associated with newer antiepileptic drugs, including lamotrigine, has not yet been investigated. Methods Using a retrospective chart review, we identified six patients with epilepsy who reported transient emergent psychological symptoms during stable, chronic lamotrigine monotherapy. Results These symptoms included anxiety, emotional lability, and irritability. In each case, the symptoms resulted in marked subjective distress and reliably occurred in the 1–2 h before the patients were due to take their next dose of medication. Conclusions Lamotrigine withdrawal symptoms exist and can occur as an end-of-dose phenomenon, even in patients on stable medication doses. End-of-dose withdrawal from lamotrigine is a clinically significant adverse effect that can hamper successful treatment with this medication.

Newer and older antiepileptic drug use in Southern Italy: A population-based study during the years 2003–2005

To analyse the prescribing pattern of newer and older antiepileptic drugs (AEDs) during the years 2003-2005. From the Caserta-1 Local Health Service database, 93 general practitioners (GPs) were recruited. Among 127,389 individuals aged > or =15 years registered in the lists of these GPs, we selected patients who received at least one AED prescription during the study period. Use of newer and older AEDs was calculated as 1-year prevalence and incidence as well as defined daily dose (DDD) per 1000 inhabitants/day. Sub-analyses by gender, age and indication of use were performed. Overall, prevalence and incidence of use remained stable for older AEDs, while it strongly increased for newer AEDs. In particular, 25% increase of incident treatments with newer AED have been reported from 2004 to 2005. The total volume of AED use remained stable during the study years, despite the proportion of newer AEDs slightly increased (from 24.6% in 2003 to 30.1% in 2005). The main indication of use was epileptic disorders for older AEDs (56% of users), and neuropathic pain for newer AEDs (69%). Prevalence and incidence of use of newer AED strongly increased during the years 2003-2005 in a general practice of Southern Italy. Significant differences are shown in the prescribing pattern of newer and older medications: older AEDs are mainly used in the treatment of epileptic disorders, while newer compounds are preferred for conditions other than epilepsy, in particular neuropathic pain.

Antiepileptic Drug-Induced Cognitive Adverse Effects

Cognitive dysfunction is frequently observed in patients with epilepsy and represents an important challenge in the management of patients with this disorder. In this respect, the relative contribution of antiepileptic drugs (AEDs) is of relevance. The fact that a considerable number of patients require AED therapy for many years, or perhaps even a lifetime, emphasizes the need to focus on the long-term adverse effects of these drugs on cognition. The most prevalent of the CNS adverse effects observed during AED therapy are sedation, somnolence, distractibility, insomnia and dizziness. Sedation, in particular, is associated with most of the commonly used AED therapies. Nevertheless, cognitive function in individuals with epilepsy may also be influenced by several factors, of which AEDs constitute only one of many putative causes. In general terms, most studies agree that some differences exist among the older AEDs with regard to the effects on cognition, and some newer generation molecules may have a better cognitive profile than older AEDs. The mechanisms of action are an obvious determinant; however, there is still a lack of evidence for differentiation between available drugs with regard to cognitive effects. Some authors have suggested that there may be different cognitive effects associated with individual drugs; however, the question as to whether there are more specific deficits related to the action of individual drugs remains unsolved. There seems to be agreement that polytherapy and high-dose treatment can produce cognitive adverse effects and when high dosages or adjunctive polytherapy is needed, the balance between benefits and disadvantages may be negatively biased against drug treatment. Thus, drug treatment requires careful balancing in the attempt to reach maximal seizure control while avoiding neurotoxic adverse effects. Finally, the mood status of the patient and clinical relevance of the information obtained by neuropsychological testing represent important variables that need to be taken into account when discussing cognitive adverse effects of AEDs.