Antiepileptic Drug Monotherapy Research Articles

No Negative Effect of Antiepileptic Drug Exposure Through Breast Milk on Cognitive Function at Age 6 Years

In a previous report of an ongoing prospective, observational, multicenter study, antiepileptic drug (AED) monotherapy (with carbamazepine,

Long-term prognosis of patients with Ehlers-Danlos syndrome and epilepsy.

Epilepsy in Ehlers-Danlos syndrome (EDS) has been reported in the literature, but there are no studies that have investigated in detail clinical and electroencephalography (EEG) features in patients with EDS, and that have compared the outcome of epilepsy in subjects with or without brain lesions. We report a series of 42 patients with EDS and epilepsy, including data that concern clinical characteristics, EEG abnormalities, brain malformations at magnetic resonance imaging (MRI) and long-term outcome. EEG, clinical information, and neuroimaging characteristics in 42 patients with EDS were analyzed at the onset of epilepsy and after long-term follow-up (at least 5 years). We subdivided the patients into two groups: group A, 26 patients without brain abnormalities; group B, 16 patients with brain lesions, often with periventricular heterotopia (PH). Group A patients: Most cases (19 of 26) presented focal epilepsy, whereas 7 of 26 were affected by generalized epilepsy; interictal EEG showed temporal or temporoparietal spikes in most cases. Twenty-three patients received antiepileptic drug (AED) monotherapy; three patients were treated with polytherapy. During follow-up, all patients were seizure-free for at least 2 years, and only one continued to receive AEDs. Group B patients: the majority presented focal epilepsy (9 of 16), but many patients had generalized epilepsy (7 of 16); interictal EEG showed usually frontal or frontotemporal spikes and waves. Many patients (12 of 16) received AED polytherapy. During follow-up, 12 patients were seizure-free, and all patients continued pharmacologic treatment. All patients without brain lesions showed a favorable response to AED monotherapy and were seizure-free after a few years of treatment. Patients with central nervous system abnormalities had a worse outcome, suggesting that the presence of brain lesions could influence the long-term evolution in these patients.

Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients.

Topiramate (TPM) is a sulfamate-substituted monosaccharide that is structurally different from other antiepileptic drugs. TPM inhibits carbonic anhydrase activity, which is associated with loss of bicarbonate from the kidney and consequently metabolic acidosis or electrolyte imbalance. The objectives of the study were to investigate the influence of TPM therapy on bicarbonate and potassium levels in adult epileptic patients. Data were collected from 59 adult patients on monotherapy or co-therapy of TPM and other antiepileptic drugs. Serum bicarbonate and potassium levels were available from all patients. Steady-state TPM trough concentrations were determined in blood samples by high-performance liquid chromatography. Data analysis was performed by SPSS software (version 17, Chicago, IL). Patients were divided into group A (duration of therapy shorter than or equal to 5 years) and group B (duration of therapy longer than 5 years). Significant difference (P < 0.05) in serum bicarbonate levels was observed between these 2 groups. Bicarbonate levels were linearly related to the TPM therapy duration. No correlation was found between the TPM dose or patient age and bicarbonate or potassium levels, as well as between therapy duration and potassium level. Linear regression analysis showed no significant association among 54 available TPM trough concentrations and bicarbonate or potassium levels. Results highlight the frequent occurrence of lower bicarbonate level associated with prolonged TPM therapy. Monitoring bicarbonate levels in patients on long-term TPM therapy might be useful.

Epilepsy in Prader-Willi syndrome: clinical, diagnostic and treatment aspects.

Epilepsy associated with Prader-Willi syndrome (PWS) represents an early and important complication, often not clearly reported and described in the literature. Consequently, there are controversial data about the clinical characteristics of epilepsy and electroencephalographic (EEG) abnormalities found in these patients. Based on recent original publications, we have reviewed the different types of seizures and EEG findings in PWS patients, the response to antiepileptic treatment, and the prognosis of epilepsy. The frequency of epilepsy in PWS patients ranges from 4% to 26%. The types of seizure include generalized tonic-clonic seizures, complex partial seizures, atypical absence, staring spells, and myoclonic, tonic and hemiclonic seizures, but the most frequent type is focal epilepsy. Status epilepticus has never been reported. EEG abnormalities are not typical but variable in different patients. However, generalized and focal discharges are the most frequently reported findings. There is no evidence of relationship between the course of epilepsy and frequency, morphology and spread of EEG discharges. However, epilepsy in PWS patients is usually responsive to antiepileptic monotherapy with rapid seizure control and a good outcome. The frequency of epilepsy is higher in PWS patients than in general populations and this complication can be a challenge for the clinicians of these patients. Prospective studies are needed to confirm the good long-term prognosis.

Malformation Risks Of Antiepileptic Drug Monotherapies In Pregnancy: An Update From The UK and Ireland Epilepsy and Pregnancy Registers (S59.001)

Malformation Risks Of Antiepileptic Drug Monotherapies In Pregnancy: An Update From The UK and Ireland Epilepsy and Pregnancy Registers (S59.001)

Malformation Risks Of Antiepileptic Drug Monotherapies In Pregnancy: An Update From The UK and Ireland Epilepsy and Pregnancy Registers (I8-2.005)

Malformation Risks Of Antiepileptic Drug Monotherapies In Pregnancy: An Update From The UK and Ireland Epilepsy and Pregnancy Registers (I8-2.005)

Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers

ObjectivesAntiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the...

Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy

Background: Epilepsy is a chronic neurological condition which may require long-term treatment with antiepileptic drugs (AEDs). The challenge in AED management is to attain freedom from seizures, without side-effects and with good quality-of-life. However, AEDs are reported to induce potential adverse effects, which can remain unnoticed over long time. In this regard, earlier studies report inconsistent results in hematological and biochemical toxicity of AEDs. The objective of the present study was to evaluate the effects of AED monotherapy and polytherapy on hematological and biochemical parameters. Methods: This was a cross-sectional, observational study carried out among patients with epilepsy (PWE) receiving AEDs. The data on baseline demographic characteristics, treatment, adverse drug reactions, hematological, and biochemical investigations were collected. Statistical analysis was performed using the SPSS version 18 and descriptive statistics such as mean and median were used to summarize the data and inferential tests like Chi-square was used to compare categorical variables between groups. Results: There were 255 PWE in mean age range of 28.68±9.29 years, with 56.54% males. A total of 78.04% had focal, 18.04% had generalized seizures and remaining 3.92% were unclassified. Majority of (55.69%) PWE received polytherapy with AEDs. Females had significantly lower levels of hemoglobin (Hb) when compared with males (p=0.000), and patients on AED polytherapy showed significant difference in low Hb (p=0.006) and high alkaline phosphatase (ALP) levels (p=0.001). Conclusions: The results of this study showed significant alterations in the levels of Hb and ALP with the use of AED polytherapy in PWE. Routine hematological and biochemical investigations may be considered during AED treatment in those patients receiving AED polytherapy.

Epilepsy in the elderly

As the elderly constitute the most rapidly growing population, epilepsy in this group is an important health issue worldwide. We surveyed the prevalence of epilepsy in two hospitals for elderly citizens in Fukuoka, Japan. The study revealed that the prevalence of epilepsy was 11.2% in 743 studied hospitalized patients. We identified 70 patients who developed epilepsy after the age of 65 years at the outpatient clinic in a university affiliated hospital. Complex partial seizures (CPS) without secondarily generalization were most frequent. The most frequent diagnosis was temporal lobe epilepsy. Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. Interictal EEG revealed focal epileptiform discharges in 66.7% of patients. Forty-two patients were on antiepileptic monotherapy and 52 patients had been seizure-free for more than 1 year. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

Study of effects of antiepileptic therapy on various biochemical and hematological parameters patients suffering of epilepsy

Background: Low therapeutic index of established antiepileptic drugs (AEDs) coupled with better understanding of the pathophysiology of seizure has encouraged the development of several novel AEDs. The conventional antiepileptics like phenytoin, phenobarbitone, valproate and carbamazepine and newer antiepileptics like levetiracetam, lamotrigine and topiramate etc. are used for epilepsy. AEDs induce potentially toxic effects over a period of time which remains undetermined over very long time. Earlier studies in this regard, states uneven results about biochemical (i.e. blood sugar level, lipid profile) and hematological (Hb%, blood cell count etc.) toxicity of AEDs. Aims: To unveil the toxic effects of AEDs when given singly or as combinations. Methods: Adult epileptics of either sex taking antiepileptic monotherapy or combination therapy for ≥ six months were enrolled. Biochemical and hematological parameters studied were compared with their age and sex matched controls, baseline and amongst groups. Statistical Analysis Used: Student’s ‘t’-test &amp; One way ANOVA followed by posthoc Tukey HSD test for pair wise comparison; p&lt;0.05 was considered significant. Results: Conventional antiepileptic combination therapy was found more toxic; p&lt;0.01 for lipid profile. Combination groups showed significant reduction in Hb% (p&lt;0.05) with no significant difference among them (p&gt;0.05). Monotherapy and conventional combination therapy caused significant reduction in platelet count (p&lt;0.01), but conventional combination therapy was found more toxic in this regard (p&lt;0.05). Conclusions: Monotherapy found less toxic with no significant effects on lipid profile, Hb%, RBC count and O 2 carrying capacity and less impact on platelets while combination therapy did not show any advantage over monotherapy and its use must be reserved only for refractory cases.

Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study

In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting. In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up. Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression. This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.

Time to 12-month remission and treatment failure for generalised and unclassified epilepsy

ObjectivesTo develop prognostic models for time to 12-month remission and time to treatment failure after initiating antiepileptic drug monotherapy for generalised and unclassified epilepsy.MethodsWe analysed data from the Standard and...

Epilepsy and mood

In their article “Temporal trends in new exposure to antiepileptic drug monotherapy and suicide-related behavior,” Dr. Pugh and colleagues1 explore the link between antiepileptic drugs (AEDs) and suicide. This has been an important and worrisome topic for people with epilepsy. In short, a patient may wonder, “Will the medications I take cause other problems?” This is so important that a Patient Page addressed this same topic in the summer of 2010, when the article by Dr. Andersohn et al.2 was published in Neurology® .

Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital.

BackgroundEpilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy.MethodsThis retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis.ResultsOut of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a treatment retention rate of 100%. The effectiveness of AED in terms of reduction of seizure frequency was highest for PHT (100%) and PHB (98%) followed by CBZ (96%) and VPA (95%). PHB and PHT were the cheapest of all AEDs (42 I$ and 56 I$/ year respectively). The costs of VPA and CBZ were two times and LTG and TOP were six to eight times higher. Adverse drug reaction (ADR) were observed among 140 (24.5%) of those with monotherapy. PHT (64%) was the most common drug to cause ADR, CBZ was at the bottom of the list to cause adverse effect (11.6%). VPA and PHB caused weight gain commonly. Adjustment of drug dose or withdrawal due to ADRs was necessary in 39% with PHT and 26% with PHB.ConclusionThough PHT and PHB are cheapest and efficacious among all, CBZ and VPA are less costly, effective and well tolerated drug for seizure control in context of Bangladesh.

Role of plasma homocysteine levels and MTHFR polymorphisms on IQ scores in children and young adults with epilepsy treated with antiepileptic drugs

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs.The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of “unknown cause” (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13μM/L (tHcy<9μM/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C.Plasma tHcy levels were not significantly related to the IQ scores (TIQ, VIQ, or PIQ). Two significant findings came out. First, patients on AED polytherapy showed significantly lower TIQ, VIQ, and PIQ scores compared with the ones with AED monotherapy (p=0.032; p=0.008; p=0.005, respectively). However, this significant difference was not observed with the plasma tHcy levels compared with AED treatment. Second, patients with the 677TT genotype showed significantly higher tHcy levels versus those with the wt ones (p=0.049). In the latter group of patients, although the mean TIQ score was lower compared with the mean TIQ score in those with the wt ones, the difference only approached statistical significance (p=0.056). To our knowledge, this is the first study investigating the relationship between tHcy levels and cognitive scores in children with epilepsy treated with AEDs. Analysis of wider samples, selective neuropsychological tests, and prospective recruitment of patients might be encouraged.

Temporal trends in new exposure to antiepileptic drug monotherapy and suicide-related behavior

Because some recent studies suggest increased risk for suicide-related behavior (SRB; ideation, attempts) among those receiving antiepileptic drugs (AEDs), we examined the temporal relationship between new AED exposure and SRB in a cohort of older veterans. We used national Veterans Health Administration databases to identify veterans aged ≥65 years who received a new AED prescription in 2004-2006. All instances of SRB were identified using ICD-9-CM codes 1 year before and after the AED exposure (index) date. We also identified comorbid conditions and medication associated with SRB in prior research. We used generalized estimating equations with a logit link to examine the association between new AED exposure and SRB during 30-day intervals during the year before and after the index date, controlling for potential confounders. In this cohort of 90,263 older veterans, the likelihood of SRB the month prior to AED exposure was significantly higher than in other time periods even after adjusting for potential confounders. Although there were 87 SRB events (74 individuals) the year before and 106 SRB events (92 individuals) after, approximately 22% (n = 16) of those also had SRB before the index date. Moreover, the rate of SRB after AED start was gradually reduced over time. The temporal pattern of AED exposure and SRB suggests that, in clinical practice, the peak in SRB is prior to exposure. While speculative, the rate of gradual reduction in SRB thereafter suggests that symptoms may prompt AED prescription.

The importance of the experiences of initial diagnosis and treatment failure when switching antiepileptic drugs

We sought to understand the issues that lead from the need to change antiepileptic drugs (AEDs) and how this may influence someone's feelings regarding swapping to another drug. We conducted semistructured interviews with 14 people with epilepsy, four months after changing from AED monotherapy. Interviews were digitally recorded, transcripts were coded independently, and thematic analysis was undertaken through group work. There were seven major themes: failure, the reason behind the failure, and the experience itself; expectations; previous experience; personality and life events; side effects; impact of diagnosis; and outcome. Clinical outcome and patients' ideas of outcome were often discordant. Each drug change arises from a position of failure that elicits strong feelings of loss of control and vulnerability in participants. Recognizing the need for counseling of targeted individuals undergoing AED change is key. Unresolved emotional issues surrounding biographical disruption following diagnosis were potent modifiers of the change process.

Effect of AED on the EEG pattern in epileptic children

Background: The value of qEEG analysis as predicting seizure exacerbation in children with new onset epilepsy is important. The aim of the work was to study the dynamics of EEG characteristics in epileptic children at different stages of antiepileptic drug (CBZ) monotherapy.

Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales. Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System—Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more atypical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD. The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine potential risks associated with other AEDs, better define the risks to the neonate that are associated with AEDs for treatment of seizures, and understand the underlying mechanisms of adverse AED effects on the immature brain.

Withdrawal of antiepileptic drugs during presurgical video-EEG monitoring: an observational study for evaluation of current practice at a referral center for epilepsy

Withdrawal of antiepileptic drugs (AEDs) before and during video-EEG-monitoring is commonly implemented to reduce time needed to register a sufficient number of seizures during presurgical evaluation. There are, however, few guidelines regarding withdrawal rate and observation time. We performed an observational study including sixty patients admitted to the national Norwegian epilepsy centre and registered tapering of AEDs and their effect on seizure rate and possible complications. The mean daily seizure rate before admission to the EMU was 0.4 (range 0.02-4) increasing to 1.1 (range 0-8) at the EMU. 29 patients (48%) followed a slow tapering rate whereas 31 (52%) had an intermediate tapering rate. There was no significant difference between the patients with a daily seizure rate during LTM of more or <0.7 seizures per day, an increase of seizure frequency from habitual to during LTM of more or <3.3 or 6.9 with regard to rate of tapering (slow vs intermediate) etiology or AED monotherapy vs polytherapy. Twenty-six patients (43%) had a sufficient number of seizures registered within 3 days to conclude regarding the presurgical evaluation. Two patients received escape treatment while 25 patients did have 24 h-seizure-clusters. There was no serious event. Less than 50% of the patients got a sufficient number of seizures for a conclusive result within 3 days. An increase in the registration period could increase the number of successful registrations.