Serum Levels Of Antiepileptic Drugs Research Articles

Antiepileptic-drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy.

OBJECTIVES:Antiepileptic-drug (AED) serum level and inflammatory biomarkers are primarily monitored/assessed during epilepsy treatment for effective seizure control; however, their correlation with seizure recurrence (SR) following AED-tapering has not been established, and this is being investigated in this study.MATERIALS AND METHODS:This prospective observational study enrolled persons with epilepsy (PWE) on AED monotherapy and going to start tapering after being seizure-free for ≥2 years. Data regarding seizure episodes, AED-treatment, and adverse events (using Liverpool Adverse Event profile [LAEP]-score) were recorded. Serum AED levels using high-performance liquid chromatography and biomarkers levels through enzyme-linked immunosorbent assay kits were estimated at AED-tapering commencement and at 6 months/SR time.RESULTS:Among 129 enrolled PWE (levetiracetam [n = 52], valproate [n = 34], carbamazepine [n = 29], and phenytoin [n = 14]), SR occurred in 23.3% during follow-up (range 12–44 months). PWE with subtherapeutic serum AED level at the onset of tapering had higher SR (P = 0.004) than those with therapeutic or higher levels. Levetiracetam-treated PWEs with SR have significantly low AED levels than PWE with no-SR (P < 0.001). PWE had significantly raised inflammatory biomarkers (interleukin [IL]-1 β, tumor necrosis factor [TNF]-α, IL-6, and high-mobility group box protein 1) and decreased IL-10 than healthy control subjects. SR and no-SR groups did not differ significantly in inflammatory markers except for higher IL-1 β and TNF-α levels in SR group (P = 0.001, 0.02, respectively). Improvement in LAEP score was observed in follow-up visits without any difference between SR and no-SR groups.CONCLUSION:Low serum AED levels (especially levetiracetam) and raised levels of TNF-α and IL-1 β during tapering commencement had a higher association with SR following AED-tapering.

Significant Association of Antiepileptic Drug Polytherapy with Decreased FT4 Levels in Epileptic Patients.

Epileptic patients have to continue anti-epileptic drugs (AED) over a long period of time which can have deleterious effects on the endocrine system including the thyroid hormones with rare check. Risk factors for the development of thyroid dysfunction are still unclear. Therefore the aim of study was to evaluate thyroid functions in epileptic patients receiving anti-epileptic drugs (AED) as monotherapy and polytherapy and to determine potential risk of low thyroid function in epileptic patients receiving treatment. This cross-sectional study included 100 epilepsy patients more than 12years of age. Serum levels of free thyroxin (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were evaluated in all subjects in addition to serum AED levels. TSH levels were found to be significantly higher in the polytherapy subgroup (p < 0.05) in comparison to the monotherapy group. 44% of the patients in the VPA monotherapy group had raised TSH levels and 41.2% of the patients on CBZ had low FT4. A significant negative correlation was observed between CBZ and FT4 (p < 0.05). Female sex and old age were additional risk factors detected for deranged thyroid function. Female patients with epilepsy, an older age and AED polytherapy were found to be associated with a higher risk of thyroid dysfunction. Thus, Thyroid function in these patients should be monitored closely. In conclusion, we observed significant changes in thyroid hormone levels in patients receiving antiepileptic treatment in both monotherapy and polytherapy. Elevated CBZ levels were significantly associated with decreased FT4 levels.

Intra Nasal Midazolam vs. Rectal Diazepam in Management of Acute Seizures in Pediatrics, Considering the Antiepileptic Drugs Monitoring

Immediate management of children's epilepsy is essential before the patient arrives to the hospital. The purpose of this study was to compare the efficacy of intranasal midazolam vs. rectal diazepam in the management of acute pediatric seizures. In this cross-sectional study, 68 patients having acute seizure were evaluated for response to treatment after receiving intra-nasal midazolam (34 patients) or rectal diazepam (34 patients). Patents were assessed by physicians at the arrival to emergency department for history taking and examination. Blood samples were assessed for valproate, phenobarbital and phenytoin levels in serum to determine previous use of antiepileptic drugs. Seizure duration and response time to treatment were evaluated along with health care utilization and were compared between study groups, by the statistical package for the social sciences software. Mean age of study participants, sex disturbance, age at onset of a seizure, type of seizure and prehospital time had not any significant differences between two groups (p>0.05). The mean response time to diazepam was 8.0±4.9 min and 6.3±2.2 min for midazolam; which had a significant difference between groups (0.001). Linear regression of serum antiepileptic drug levels in association of response time in each group was not significant in all case (p>0.05), expect the lamotrigine serum level in midazolam group (p=0.029). Intranasal midazolam was seen to have a better effect than rectal diazepam in the management and treatment of acute seizures in children; while antiepileptic drugs monitoring want helpful in assessing the absolute effect.

Author response: Clinical utility of therapeutic drug monitoring of antiepileptic drugs.

I appreciated Dr. Sethi's commentary on our recently published article as he raises a number of interesting points.1 Certainly, intraindividual variability is another complicating aspect of therapeutic drug monitoring (TDM) in epilepsy care and, while outside the scope of our review, should be taken into account by all clinicians who choose to incorporate serum antiepileptic drug levels into their clinical decision-making. For my personal practice, I tend to agree that the clinical utility of serum antiepileptic drug levels is limited and that dosing adjustments are best made based on clinical response (seizure control and reported adverse effects). Although our systematic review did identify some studies showing evidence for TDM, the higher quality studies did not show convincing evidence supporting a clinical benefit. In general, we clinicians now have a wealth of diagnostic options available to us, and it is easy to forget that the patient's reported symptoms and clinical examination are almost always the most important outcome measures.

Drug-Induced Liver Injury in Critically Ill Children Taking Antiepileptic Drugs: A Retrospective Study

Antiepileptic drugs are among the leading causes of drug-induced liver injury (DILI). Due to critical illness, children admitted to intensive care units are more prone to DILI. We attempted to elucidate the association between antiepileptic drug use and the associated factors resulting in DILI in a pediatric intensive care unit of a tertiary care hospital. We carried out an observational retrospective study on children receiving antiepileptic drugs. Details on their demographic characteristics, drugs, serum levels of antiepileptic drugs and liver function tests, and hospital stay were recorded. Council for International Organizations of Medical Sciences definitions were adhered to when defining DILI. LiverTox (https://livertox.nih.gov) and DILIrank were used to assess the risks of hepatotoxicity of the concomitant drugs. Regression models were developed for predicting DILI. Five out of 9 patients taking phenobarbitone (55.6%), 9 out of 12 taking phenytoin monotherapy (75%), 7 out of 10 taking phenytoin/phenobarbitone (70%), all 3 receiving phenytoin/phenobarbitone/valproate sodium, and 1 with phenytoin/carbamazepine developed DILI either in the form of hepatocellular injury or liver biochemical test abnormalities. None of the patients had cholestatic or mixed type of liver injury. All the critically ill children received at least 2 concomitant drugs with hepatotoxic potential. Concomitant category B hepatotoxic drugs and toxic drug levels were significantly associated with increased risk of DILI. Similarly, a trend was observed for less-DILI-concern concomitant drug class and toxic drug levels when the drugs were analyzed by DILIrank classification. A significant proportion of critically ill children taking antiepileptic drugs experience DILI. Guidelines recommending use of drugs with reduced risk of potential hepatotoxicity for various concomitant disease states in such children admitted to intensive care units receiving antiepileptic drugs are urgently needed.

Kumaraswamy Distribution in Analyzing the Health-related Quality of Life and Effective Factors in Elderly Patients with Epilepsy

Background: Epilepsy, which develops in the elderly, is recognized as a major health burden. Although health-related quality of life (HRQoL) is an essential element in the medical treatment of elderly patients with epilepsy, it is a question whether epilepsy and its treatment effectively influence the quality of life (QoL) in the elderly. Objectives: The current study aimed at evaluating the relationship between demographic and clinical aspects of epilepsy in HRQoL of elderly patients. Since HRQoL scores are bounded, the Kumaraswamy (Kum) regression model was used to analyze the data. Methods: The current study was conducted on 766 elderly patients diagnosed with epilepsy taking at least one antiepileptic drug (AED) selected from six neurologic clinics in Iran. In addition to demographic information, the Liverpool seizure severity scale (LSSS), medication adherence report scale (MARS-5), and quality of life in epilepsy (QoLIE-31) questionnaire were completed for patients. Data were analyzed using multiple linear regression (MLR) and the Kum regression models. Results: Most of the patients included in the study had focal (70.2%) epilepsy. Mean duration of disease was 17.71 ± 4.56 years and the average number of seizures was 3.4 ± 3.2 episodes per month. The Kum regression model indicated that seizure frequency (β = -0.157, P < 0.0001) and LSSS score (β = -0.003, P = 0.009) were significant and negative predictors of overall QoLEI-31 score; MARS-5 score was a positive predictor of overall QoLEI-31 score (β = 0.014, P = 0.002). However, disease duration and serum AED level had no significant effects on overall QoLEI-31 score. Conclusions: The findings suggested that increased seizure frequency and severity were associated with lower QoL and medication adherence was directly associated with HRQoL. The Kum regression could be a suitable alternative to the methods currently used in the analysis of HRQoL data.

Health-related quality of life and medication adherence in elderly patients with epilepsy.

Considering the high prevalence of epilepsy in the elderly and the importance of maximising their quality of life (QoL), this study aimed to investigate the relationship between medication adherence and QoL, and the mediating effects of medication adherence on the association between serum antiepileptic drug (AED) level and seizure severity with QoL in elderly epileptics. In a longitudinal study, 766 elderly patients with epilepsy who were prescribed a minimum of one antiepileptic drug were selected by convenience sampling method. A Medication Adherence Report Scale (MARS-5) questionnaire was completed at the baseline. Seizure severity and QoL were assessed after six months using the Liverpool Seizure Severity Scale (LSSS) and the QoL in Epilepsy (QOLIE-31) questionnaires respectively. Serum level of AED was also measured at six-month follow-up. Medication adherence was significantly correlated with both seizure severity (β = -0.33, p < 0.0001) and serum AED level (β = 0.29, p < 0.0001) after adjusting for demographic and clinical characteristics. Neither QoL nor its sub-classes were correlated with seizure severity. In addition, a significant correlation was not observed between serum AED level and QoL. However, medication adherence was significantly correlated with QoL (β = 0.30, p < 0.0001). The mediating effects of medication adherence on the association between serum AED level (Z = 3.39, p < 0.001) and seizure severity (Z = -3.47, p < 0.001) with QoL were supported by the Sobel test. This study demonstrates that medication adherence has a beneficial impact on QoL in elderly epileptics. Therefore, adherence to treatment should be monitored to improve their QoL.

Changes in Serum Valproate and Levetiracetam Levels Related to Sex Steroids in Adolescent Girls

Abstract Background The goal of this study was to explore the changes in serum antiepileptic drug levels and their relation with sex steroid levels during the menstrual cycles of adolescent girls. In addition, valproate and levetiracetam were compared in terms of their effects on body mass index, ovulation, and sex steroid levels. Methods Adolescent girls using valproate (n = 16) and levetiracetam (n = 9) were included in the study. Serum antiepileptic drug, progesterone, and estradiol levels were analyzed in two periods, when the levels of sex hormones might be the highest (midluteal phase) and the lowest (early follicular phase). Results Serum antiepileptic drug levels were not significantly different between the two periods in both antiepileptic drug groups. Serum antiepileptic drug levels during menstruation increased in 69.2% of the valproate group, whereas they decreased in 88.9% of the levetiracetam group ( P = 0.011). A positive correlation between serum valproate and progesterone levels ( r = 0.767, P = 0.001) and between levetiracetam and estradiol levels ( r = 0.259, P > 0.05) was present in the menstrual phase. Body mass index, body mass index percentile, z score, and ovulation rates were not different between the two groups. Conclusions This study indicates a strong correlation between valproate and progesterone levels in the early follicular phase of the menstrual cycle. The findings of this study also suggest that valproate and levetiracetam have different relationships with sex steroid levels, during menstrual cycle. Especially in catamenial seizures, taking this interaction into account may be beneficial.

Randomized Controlled Trial of Melatonin for Sleep Disturbance in Dravet Syndrome: The DREAMS Study

Dravet syndrome is a severe developmental and epileptic encephalopathy, in which 75% of patients have sleep disturbance. Melatonin is often used for sleep problems in childhood; however, there is no quality evidence supporting its use in Dravet syndrome. We hypothesized that melatonin would increase total sleep and quality of life for patients with Dravet syndrome. A double-blind crossover randomized placebo-controlled trial was conducted, comparing 6 mg regular-release melatonin to placebo for patients with Dravet syndrome and sleep disturbance. The primary outcome measure was total sleep measured by actigraphy, with secondary outcomes including wakefulness after sleep onset (WASO), Sleep Disturbance Scale in Children and Quality of Life in Children with Epilepsy 55 questionnaires, caregiver reports of clinical change, seizure diary and serum antiepileptic drug levels. We also compared actigraphy data of patients with Dravet syndrome to an age-matched healthy control group. A total of 13 patients completed the study. There was no difference in total sleep or WASO between melatonin and placebo. However, of the 11 patients for whom caregivers reported a clear clinical difference between treatments (blinded), 8 reported improvement on melatonin (P < .05). Interestingly, when compared to patients in the control group, patients with Dravet syndrome had significantly increased total sleep (P = .002). Melatonin did not increase total sleep; however, blinded caregiver reports indicate treatment with melatonin provided considerable clinical benefit for some patients with Dravet syndrome and sleep disturbance. Registry: Australian Government Department of Health, Therapeutic Goods Administration under the Clinical Trials Notification Scheme (protocol number 2241).

AntiEpileptic drug Monitoring in PREgnancy (EMPiRE): a double-blind randomised trial on effectiveness and acceptability of monitoring strategies.

Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control. To determine if, in pregnant women with epilepsy on AEDs, additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels. A double-blind, randomised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken. Stratified block randomisation with a 1 : 1 allocation method was carried out. Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK. Pregnant women with epilepsy on one or more of the following AEDs: lamotrigine, carbamazepine, phenytoin or levetiracetam. Women with a ≥ 25% decrease in serum AED level from baseline were randomised to therapeutic drug monitoring or clinical features monitoring strategies. In the therapeutic drug monitoring group, clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control. In the clinical features monitoring group, AED dosage adjustment was based only on clinical features. Primary outcome - seizure deterioration, defined as time to first seizure and to all seizures after randomisation per woman until 6 weeks post partum. Secondary outcomes - pregnancy complications in mother and offspring, maternal quality of life, seizure rates in cohorts with stable serum AED level, AED dose exposure and adverse events related to AEDs. Analysis of time to first and to all seizures after randomisation was performed using a Cox proportional hazards model, and multivariate failure time analysis by the Andersen-Gill model. The effects were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes were reported as mean differences (MDs) or odds ratios. A total of 130 women were randomised to the therapeutic drug monitoring group and 133 to the clinical features monitoring group; 294 women did not have a reduction in serum AED level. A total of 127 women in the therapeutic drug monitoring group and 130 women in the clinical features monitoring group (98% of complete data) were included in the primary analysis. There were no significant differences in the time to first seizure (HR 0.82, 95% CI 0.55 to 1.2) or timing of all seizures after randomisation (HR 1.3, 95% CI 0.7 to 2.5) between both trial groups. In comparison with the group with stable serum AED levels, there were no significant increases in seizures in the clinical features monitoring (odds ratio 0.93, 95% CI 0.56 to 1.5) or therapeutic drug monitoring group (odds ratio 0.93, 95% CI 0.56 to 1.5) associated with a reduction in serum AED levels. Maternal and neonatal outcomes were similar in both groups, except for higher cord blood levels of lamotrigine (MD 0.55 mg/l, 95% CI 0.11 to 1 mg/l) or levetiracetam (MD 7.8 mg/l, 95% CI 0.86 to 14.8 mg/l) in the therapeutic drug monitoring group than in the clinical features monitoring group. There were no differences between the groups on daily AED exposure or quality of life. An increase in exposure to lamotrigine, levetiracetam and carbamazepine significantly increased the cord blood levels of the AEDs, but not maternal or fetal complications. Women with epilepsy perceived the need for weighing up their increased vulnerability to seizures during pregnancy against the side effects of AEDs. Fewer women than the original target were recruited. There is no evidence to suggest that regular monitoring of serum AED levels in pregnancy improves seizure control or affects maternal or fetal outcomes. Further evaluation of the risks of seizure deterioration for various threshold levels of reduction in AEDs and the long-term neurodevelopment of infants born to mothers in both randomised groups is needed. An individualised prediction model will help to identify those women who need close monitoring in pregnancy. Current Controlled Trials ISRCTN01253916. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 23. See the NIHR Journals Library website for further project information.

Correlation Between Serum Level of Antiepileptic Drugs and their side-effects

Phenytoin can cause a range of dose-related and idiosyncheratic adverse effects.

Interactions between cannabidiol and commonly used antiepileptic drugs.

To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs. In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate. Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serum levels were seen with increasing CBD dose. Increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose were seen in adults. Except for clobazam and desmethylclobazam, all noted mean level changes were within the accepted therapeutic range. Sedation was more frequent with higher N-desmethylclobazam levels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01). Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD.

Correlation between adherence to antiepileptic drugs and quality of life in patients with epilepsy: A longitudinal study.

This study aimed to investigate whether the score of self-reported medication adherence using the Medication Adherence Report Scale (MARS-5) correlates with the serum level of antiepileptic medication, as well as whether the MARS-5 score can predict the quality of life (QoL) in patients with epilepsy. A longitudinal study was carried out. The patients with epilepsy who were prescribed a minimum of one antiepileptic drug were recruited (n=807). Each participant completed a background information sheet and the MARS-5 at baseline, followed by the Liverpool Seizure Severity Scale (LSSS) and Quality of Life in Epilepsy (QOLIE-31) questionnaire at 18-month follow-up. In addition, the serum level of antiepileptic medications was measured at the follow-up. The MARS-5 score was negatively associated with the LSSS score (B=-0.089, SE=0.009, p<0.001) and positively correlated with the serum level of antiepileptic medications (B=3.200, SE=0.416, p<0.001), after adjusting for demographics and clinical characteristics. The serum level of antiepileptic drugs was significantly correlated with the overall QOLIE-31 score (B=3.118, SE=1.417, p=0.03). The MARS-5 score was significantly correlated with the overall QOLIE-31 scores and all the scores in the subcategories. In addition, the MARS-5 score was in line with the correlation between the LSSS and QOLIE-31 scores (Z=4.20, p<0.001) and between serum antiepileptic medication levels and QOLIE-31 score (Z=3.98, p<0.001). The MARS-5 score can predict the QoL in patients with epilepsy for up to 18months. Therefore, healthcare providers may predict the QoL and drug adherence using the MARS-5 score, in order to design personalized interventions.

Interaktionen zwischen hormoneller Kontrazeption und antikonvulsiver Medikation

The use of oral contraceptives (OCs) in combination with antiepileptic drugs (AEDs) in women with epilepsy (WWE) can lower efficiency both in terms of, for example, seizure deterioration and unintended pregnancies. We investigated the bidirectional interactions of progestins in OCs and monotherapy with lamotrigine (LTG), valproate (VPA) or carbamazepine (CBZ). The goal was to investigate the impact of these interactions in general and additionally to analyze differences in AED serum levels during intake.

Bone status in patients with epilepsy: relationship to markers of bone remodeling.

Patients with epilepsy and treated with antiepileptic drugs (AEDs) may develop metabolic bone disease; however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90 ± 5.62 years; duration of treatment with AEDs: 10.57 ± 3.55 years) and 40 matched healthy controls. Bone mineral content (BMC) and bone mineral densities (BMD) of the femoral neck and lumbar spine were measured using dual-energy X-ray absorptiometry (DEXA). Blood samples were analyzed for calcium, magnesium, phosphate, alkaline phosphatase (ALP), 25-hydroxy vitamin D (25OHD), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG), and OPG/RANKL ratio (markers of bone remodeling). Compared to controls, patients had lower BMD, BMC, Z-score, and T-score at the femoral neck and lumbar spine (all p < 0.001). Seventy-two percent and 29.33% of patients had osteoporosis of the lumbar spine and femoral neck. Patients had significantly lower serum calcium, 25(OH)D, and OPG and higher ALP, sRANKL levels, and sRANKL/OPG (all p < 0.001). Fifty-two percent of patients had hypocalcemia, 93% had hypovitaminosis D, 31% had high levels of sRANKL, and 49% had low levels of OPG. No differences were identified between DEXA and laboratory results in relation to the type, dose, or serum levels of AEDs. BMD at the femoral neck and lumbar spine were found to be correlated with the duration of illness (p = 0.043; p = 0.010), duration of treatment with AEDs (p < 0.001; p = 0.012), and serum levels of 25(OH)D (p = 0.042; p = 0.010), sRANKLs (p = 0.005; p = 0.01), and OPG (p = 0.006; p = 0.01). In linear regression analysis and after adjusting for gender, age, weight, duration, and number of AEDs, we observed an association between BMD, 25(OH)D (p = 0.04) and sRANKL (p = 0.03) concentrations. We conclude that AEDs may compromise bone health through disturbance of mineral metabolism and acceleration of bone turnover mechanisms.

The influence of gender, age, smoking habit and body weight on serum levels of antiepileptic drugs under naturalistic conditions

The influence of gender, age, smoking habit and body weight on serum levels of antiepileptic drugs under naturalistic conditions

Progesterone therapy in women with epilepsy

BackgroundProgesterone with its anti-seizure effect plays a role in the pathophysiology of catamenial epilepsy which affects 31–60% of epileptic women. In this study, an attempt to treat women suffering from catamenial epilepsy with progesterone, as an adjuvant drug, was made. MethodsThe treatment was given to 36 women aged 20–40 years (mean age: 30.75±6.05) with seizures in the entire second half of the menstrual cycle, who were found to have low serum levels of progesterone on days 22, 27, 28 of the cycle in comparison with a control group of healthy women. The patients were administered progesterone in a daily dose of 50mg on days 16–25 of each cycle. The serum levels of antiepileptic drugs were assayed. The period of progesterone therapy ranged from 3 to 45 months (17.7 on average). ResultsThree patients were free of secondary generalized seizures, and one – of simple partial seizures. Adecline in the frequency of primary and secondary generalized seizures by 20–96% (55.9% on average) was accomplished in 18 patients (primary generalized by 20–96% – 54.7% on average, and secondarily generalized by 38–85% – 59% on average).Adecline in the frequency of complex partial seizures by 38–87% (63.1% on average) was achieved in 15 women. In 1 patient, the frequency of myoclonic seizures decreased by 46%. There was no improvement in 5 women (3 patients with generalized, 1 with complex partial and 1 with simple partial seizures). An exacerbation of seizure frequency occurred in 5 patients. Adverse effects were not found in any of the subjects. The average concentrations of antiepileptic drugs during hormonal therapy were in the therapeutic range. ConclusionProgesterone combined with antiepileptic therapy was well tolerated and resulted in a significant reduction of seizure frequency in majority of patients with catamenial epilepsy.

Cost-effectiveness analysis for the use of serum antiepileptic drug level monitoring in children diagnosed with structural-metabolic epilepsy

Treatment with antiepileptic drugs is commonly guided by serum level monitoring. Such monitoring requires expensive laboratory equipment and products. However, well-conducted studies on the cost-effectiveness of therapeutic drug monitoring for antiepileptic drugs are lacking particularly in patients with structural-metabolic epilepsy. The study aims to assess the cost-effectiveness of serum level monitoring services in the management of children with structural-metabolic epilepsy during the first year of diagnosis. A retrospective cost-effectiveness analysis was conducted from the provider perspective. It included patients attended a paediatric neurology clinic. The effectiveness measures used in this analysis were the number of patients that achieved ≥50% reduction in seizure frequency, and the number of patients with 3-month seizure free. Medical records of the patients were reviewed for the required information. Medical chart/billing data obtained from the hospital were collected to estimate the resources used (One Malaysian Ringgit MYR is equivalent to 0.31 USD). The recruited children were followed for one year following their first visit. The average cost effectiveness ratio for the monitored patients (MYR 2735 per patient that achieved a ≥50% reduction in seizure frequency) was lower than that for non-monitored patients (MYR 2921 per patients that achieved a ≥50% reduction in seizure frequency), with incremental cost-effectiveness ratio of MYR 2357 per one additional patient that achieved a ≥50% reduction in seizure frequency. The average cost effectiveness ratios for monitored and non-monitored group were MYR 8279 and MYR 6433 per patient with a 3-month seizure-free period, respectively, with incremental cost-effectiveness ratio of MYR 29,666 per one additional patient with a 3-month seizure-free period. In terms of the effectiveness measures used, serum level monitoring of antiepileptic drugs was found to be cost-effective. However, the incremental cost-effectiveness ratio was found to be sensitive to the cost of management.

Practices Associated with Serum Antiepileptic Drug Level Monitoring at a Pediatric Neurology Clinic

Objectives: To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural–metabolic epilepsy. Methods: It was a retrospective chart review and included children aged ≥2 years old with structural–metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records. Results: Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, “check level” and “recheck level” were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician’s actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled. Conclusions: More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists

26.Causes of low serum levels of antiepileptic drugs in children

26.Causes of low serum levels of antiepileptic drugs in children