Anticonvulsant Levels Research Articles

Inappropriate requests for serum anti-epileptic drug levels in hospital practice.

Serum anti-epileptic drug (AED) levels are indicated to assess AED adherence or toxicity, and are applicable to only a few AEDs. Expert consensus views on the clinical role of serum AED levels are summarized in the evidence-based guidelines published by the Scottish Intercollegiate Guidelines Network. To examine local compliance with these guidelines. Retrospective case-note audit. We included all serum AED level measurements requested from our hospital over two months. Our audit standards were first, that serum AED levels should be requested only for suspicion of poor AED adherence or toxicity ('indication-compliant'), and secondly, for 'full compliance', that 'indication-compliant' requests should be made only for AEDs with established dose-response and dose-toxicity relationships (phenytoin, carbamazepine, phenobarbitone). There were 114 measurements in 102 patients. Serum AED level requests were for phenytoin (n = 50), valproate (n = 27), carbamazepine (n = 22), lamotrigine (n = 8), phenobarbitone (n = 7), and were made by physicians (n = 46), paediatricians (n = 30), neurologists (n = 15), neurosurgeons (n = 14), psychiatrists (n = 7), and intensivists (n = 2). AED toxicity was queried in 29 requests (25%), and adherence in 10 (9%); thus 34% of requests were 'indication-compliant'. However, 16 of these were for valproate or lamotrigine; thus only 23 requests (20%) were 'fully compliant'. Clinical management changed in only 17 of the 47 patients whose levels fell outside target ranges, and only two of these followed indication-compliant AED measurement. The audit identified a failure locally to comply with standard evidence-based guidelines. If, as is likely, this reflects practice elsewhere in the UK, there are potentially major clinical management and resource implications.

Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study

Purpose: To establish the long-term efficacy and tolerability of vagus nerve stimulation (VNS) in children with a Lennox-like syndrome. Method: This study was a longitudinal observational prospective cohort analysis. Baseline: 6 months. Follow-up: 24 months. Screening (baseline and every 6 months): MRI (baseline only), EEG, neuropsychological evaluation, ECG and blood sampling for antiepileptic drug levels. Nineteen children are included. Results: A seizure frequency reduction of 20.6% was found at the end of the follow-up period. No relationship was detected between the length of the stimulation period and the reduction in the seizure frequency. 21% of the patients showed a reduction in seizure frequency of 50% or more. The seizure severity showed improvement in the first 12 months of treatment. The largest seizure reduction was found in the patients with highest frequency of background activity at the baseline EEG. Neuropsychological findings: no negative impact on behaviour, moderate improvement in function, behaviour and mood. Largest seizure reduction was found in the group with the highest baseline mental function. The scores for mental age improved independently of the seizure control. Twelve patients (63%) experienced minor side effects, which subsided after 1 month. Conclusion: (1) There was a significant reduction in seizure frequency and severity. (2) No serious side effects were recorded. (3) No negative effects on cognition or quality of life were apparent. (4) Patients with highest baseline mental functioning showed the highest seizure reduction. (5) Those patients with less disturbed EEG (high background activity and less interictal epileptic activity) showed the highest seizure reduction.

Mortalidad en niños con epilepsia. Estudio clínico prospectivo

Mortality in patients with epilepsy is higher than the general population, but the data about children is not too extends. OBJECTIVES. To determine the risk of dying in epileptic children, the associated factors and the cause of death, as well as to target the support given to the family.From 1996 to 2002, sixteen children with epilepsy controlled in our centre died. Fifteen of them were included in our research according to a previous protocol. The data was token from our data bank, the clinical file and parents interview.The standard mortality rate was 3.21 (95% CI: 1.48 4.95). The main group had an early onset on their illness. Thirteen children had remote symptomatic epilepsy. Eleven had resistant or catastrophic epilepsy. The EEG was specific for epilepsy in 11 cases. Nine children were receiving politherapy. Eight patients had received three or more therapeutic schemes. Eight had pre mortem therapeutic blood levels of antiepileptic drugs. Ten patients die because of infection and five because of a sudden unexpected death. In one of them the sudden unexpected death was definite and was given in a pregnant teenager with a juvenile myoclonic epilepsy. Other boy died soon after an earthquake. The assistance to the mourning elaboration was useful for the family.This children has a high risk of dying, it is associated to on early onset of severe, active, resistant and catastrophic epilepsy. The entire control of crisis should be the main target of treatment.

Antidepressive treatment in patients with temporal lobe epilepsy and major depression: a prospective study with three different antidepressants

<h2>Abstract</h2> Major depression (MD) is underdiagnosed and undertreated in patients with temporal lobe epilepsy (TLE). Side effects of some antidepressants, like increased risk of seizures and drug–drug interactions with anticonvulsants, contribute to undertreatment of MD in patients with TLE. We analyzed post hoc the data from 2 years of treatment of inpatients with MD and TLE. Seventy-five patients received standard treatment with citalopram, mirtazapine, or reboxetine, respectively, at recommended dosage. Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20–30 weeks. Plasma levels of anticonvulsants were examined at admission and discharge. Seizures were documented. The antidepressive treatment was efficacious in all antidepressant groups. No case of serious adverse event or drug interaction occurred. There was no increase in frequency or severity of seizures. At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram. Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4.

Appropriateness of serum level determinations of antiepileptic drugs.

To assess the appropriateness of the determination of the serum levels of the antiepileptic drugs (AEDs) phenytoin, valproic acid and carbamazepine in inpatients of a tertiary care institution. We performed a retrospective analysis of 602 AED serum level determinations. Appropriateness criteria regarding indication and timing were defined a priori using existing criteria from the literature. The main outcome measure was the proportion of serum levels with an appropriate indication and sampling time. Of 602 levels assessed, 463 (77%; 95% confidence interval [95% CI], 74-80%) had an appropriate indication with a range of 68% to 84% for individual AEDs; overall, 65% (95% CI: 61-69%) met the criteria for appropriate timing. Combining the two criteria, 268 (48%; 95% CI: 44-52%) AED level measurements were assessed as appropriate. Of 139 (23%, 95% CI: 20-27%) levels assessed as having an inappropriate indication, the majority (77%) were performed for routine monitoring. Less than half of all AED measurements met our criteria for appropriate AED level determinations. This creates unnecessary costs. Our data indicate the need for means to improve the rational use of AED serum level determination.

Antidepressive treatment in patients with temporal lobe epilepsy and major depression: a prospective study with three different antidepressants

Major depression (MD) is underdiagnosed and undertreated in patients with temporal lobe epilepsy (TLE). Side effects of some antidepressants, like increased risk of seizures and drug–drug interactions with anticonvulsants, contribute to undertreatment of MD in patients with TLE. We analyzed post hoc the data from 2 years of treatment of inpatients with MD and TLE. Seventy-five patients received standard treatment with citalopram, mirtazapine, or reboxetine, respectively, at recommended dosage. Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20–30 weeks. Plasma levels of anticonvulsants were examined at admission and discharge. Seizures were documented. The antidepressive treatment was efficacious in all antidepressant groups. No case of serious adverse event or drug interaction occurred. There was no increase in frequency or severity of seizures. At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram. Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4.

Appropriateness of serum level determinations of antiepileptic drugs.

To assess the appropriateness of the determination of the serum levels of the antiepileptic drugs (AEDs) phenytoin, valproic acid and carbamazepine in inpatients of a tertiary care institution. We performed a retrospective analysis of 602 AED serum level determinations. Appropriateness criteria regarding indication and timing were defined a priori using existing criteria from the literature. The main outcome measure was the proportion of serum levels with an appropriate indication and sampling time. Of 602 levels assessed, 463 (77%; 95% confidence interval [95% CI], 74-80%) had an appropriate indication with a range of 68% to 84% for individual AEDs; overall, 65% (95% CI: 61-69%) met the criteria for appropriate timing. Combining the two criteria, 268 (48%; 95% CI: 44-52%) AED level measurements were assessed as appropriate. Of 139 (23%, 95% CI: 20-27%) levels assessed as having an inappropriate indication, the majority (77%) were performed for routine monitoring. Less than half of all AED measurements met our criteria for appropriate AED level determinations. This creates unnecessary costs. Our data indicate the need for means to improve the rational use of AED serum level determination.

Identification and treatment of obstructive sleep apnea in adults and children with epilepsy: a prospective pilot study

Objective To determine the effect of treating obstructive sleep apnea (OSA) on seizure frequency in adults and children with epilepsy in a prospective study. Several case series documented an improvement in seizure control with treatment of coexisting OSA, but published series did not sample a clinic population, were not prospective in design, and did not account for concurrent changes in antiepileptic drug (AED) doses or levels. Patients and methods Adult patients and the parents of pediatric patients seen in the University of Michigan Epilepsy and Pediatric Neurology Clinics were given validated questionnaires. Thirteen adults (aged 20–56) and 5 children (aged 14–17) were selected for polysomnography (PSG) based on frequency of seizures and risk for OSA. Seizure frequency was compared during 8-week baseline and treatment phases and AED levels were done to document stability in medication levels. Results Six of 13 adults and 3 of 5 children met PSG criteria for OSA. Three adults and 1 child were treated with continuous positive airway pressure (CPAP), were tolerant of the device, and had no change in AED doses; all four had at least a 45% reduction in seizure frequency during CPAP treatment. One adult was treated with an oral appliance with a reduction in nocturnal seizures only, and 2 adults and 2 children were intolerant of CPAP. Conclusions Treatment of OSA in patients with epilepsy may improve seizure control and a large randomized placebo-controlled trial appear warranted.

Epilepsy and comorbidity: infections and antimicrobials usage in relation to epilepsy management

Infections are probably the most common preventable cause of epilepsy worldwide. There are concerns that endemic infections and infestations, such as malaria and neurocysticercosis, could be responsible for the increased incidence of epilepsy in the developing world. Cases of epilepsy associated with neurocysticercosis are also being seen increasingly in developed countries due to migration from, and travel to, endemic areas. When prescribing antimicrobial agents in patients with epilepsy a number of issues need to be considered, such as potential adverse effects on seizure control and interactions with concomitant antiepileptic drugs (AEDs). Some antimicrobial agents, including penicillins, cephalosporins, carbapenems, quinolones and antimalarials, can have proconvulsant activity and may precipitate seizures, even in patients who do not have epilepsy. Moreover, many antimicrobials increase or decrease the plasma levels of AEDs, whereas some AEDs may adversely affect the efficacy of antimicrobials.

Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice—an isobolographic analysis

The aim of this study was the isobolographic evaluation of interactions between three non-barbiturate intravenous anesthetics and conventional antiepileptic drugs in the maximal electroshock-induced seizures in mice. Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Plasma levels of antiepileptic drugs were measured by immunofluorescence. Obtained results indicate that ketamine acts synergistically with valproate and carbamazepine. Also the combinations of propofol and valproate or phenobarbital led to synergistic interactions. An antagonism was found between etomidate and carbamazepine or phenobarbital. On the other hand, interactions between diphenylhydantoin and injectable anesthetics proved to be additive. The only exception was the combination of diphenylhydantoin and propofol (1:3). Pharmacokinetic phenomena do not seem to interfere with the observed interactions, since none of anesthetics influenced the free plasma concentrations of antiepileptic drugs. Referring to undesired effects, only propofol impaired long-term memory. Although propofol did not disturbed motor coordination, it enhanced motor impairment caused by carbamazepine and diphenylhydantoin. Results of the present study suggest that etomidate needs to be avoided in epileptic patients due to a possibility of negative interactions with some antiepileptic drugs and seizure precipitation.

Refractory Epilepsy

Refractory Epilepsy

Antiepileptic drug development for "therapeutic orphans".

Epilepsy is the most common serious neurological disorder among children. Excluding the elderly, the incidence of epilepsy is highest among children. About half of children with epilepsy have epilepsy syndromes that have unique onset in childhood. Clinical drug trials of antiepileptic drugs (AEDs) among children have been primarily performed using drugs developed for the larger adult partial epilepsy market. The current AED drug development system essentially renders children with epilepsy "therapeutic orphans" who can only benefit from AED development if a drug developed for adult partial epilepsy happens to also be effective for a pediatric epilepsy syndrome. The rapid evolution of different seizure types and childhood epilepsy syndromes, and rapid changes in baseline neurological status, make distinguishing clinical changes due to study drugs in clinical trials and the natural history of the epilepsy syndrome difficult. Unique ethical issues (e.g., informed consent), practical and logistical issues (e.g., serum AED level monitoring with microassay methods), as well as major financial and regulatory disincentives for the pharmaceutical industry are additional barriers to need-based AED development for children. A government-funded pediatric epilepsy group or consortium to conduct clinical trials similar to the successful Children's Oncology Group (COG) and regulations plus financial incentives that encourage the pharmaceutical industry to develop AEDs specifically for children are needed.

Postictal serum levels of antiepileptic drugs for detection of noncompliance

Medication noncompliance (NC) is thought to be a major cause of insufficient seizure control. In an explorative study we investigated whether postictal serum levels (PISLs) of antiepileptic drugs (AEDs) are a reliable indicator of NC. Young adults with epilepsy on a stable AED regimen were asked to contact medical service as soon as possible when a seizure occurred to obtain serum levels of their AEDs. PISLs were compared with the mean value of two routine serum levels of the same medication. PISLs lower than 50% of the individual reference value were regarded as an indicator of NC. PISL samples in 61 seizures of 52 patients treated mainly with carbamazepine, valproic acid, or lamotrigine were evaluated. A drop in serum levels >50% indicating NC was noted in 44.3% of the seizures. Determination of PISLs seems to be a simple and useful method for detecting or ruling out irregular intake patterns as a cause of “breakthrough” seizures.

Influence of sexual hormone antagonists on the anticonvulsant action of conventional antiepileptic drugs against electrically- and pentylenetetrazol-induced seizures in mice

The present results refer to the action of three gonadal steroid antihormones, tamoxifen (TXF, an estrogen antagonist), cyproterone acetate (CYP, an antiandrogen) and mifepristone (MIF, a progesterone antagonist) on seizure phenomena in mice. TXF and CYP at their lowest protective dose in the electroconvulsive threshold test, enhanced the antiseizure efficacy of some antiepileptic drugs. TXF (20 mg/kg) potentiated the protective activity of valproate, diphenylhydantoin and clonazepam, but not that of carbamazepine or phenobarbital, against maximal electroshock-induced convulsions in female mice. CYP (40 mg/kg) enhanced the anticonvulsant action of valproate, carbamazepine, diphenylhydantoin and clonazepam, but not that of phenobarbital, against maximal electroshock in male animals. MIF failed to affect the electroconvulsive threshold or the efficacy of antiepileptic drugs in maximal electroshock. The effect of TXF or CYP upon the electroconvulsive threshold and on the action of antiepileptics was not reversed by sex steroid hormones (estradiol, testosterone, progesterone). However, the TXF-induced elevation of the electroconvulsive threshold was abolished by bicuculline, N-methyl- d-aspartic acid and kainic acid, and partially reversed by aminophylline, strychnine being ineffective in this respect. The action of CYP on the threshold for electroconvulsions was partially reversed by bicuculline and aminophylline. Both glutamatergic agonists and strychnine remained ineffective in this respect. Moreover, the action of TXF or CYP on the activity of antiepileptics was not influenced by strychnine, and reversed to various extents by the remaining convulsants. In contrast to maximal electroshock, none of the three antihormones affected the protective action of antiepileptic drugs against pentylenetetrazol-induced seizures in mice. Neither TXF nor CYP altered the free plasma levels of antiepileptic drugs, so a pharmacokinetic interaction is not probable. The combined treatment of the two antihormones with antiepileptic drugs, providing 50% protection against maximal electroshock, did not affect motor performance in mice, and did not result in significant long-term memory deficits. Our data indicate that steroid receptor-mediated events may be indirectly associated with seizure phenomena in the central nervous system and can modulate the protective activity of some conventional antiepileptic drugs.

Interaction of astemizole, an H 1 receptor antagonist, with conventional antiepileptic drugs in mice

Histamine is one of the aminergic neurotransmitters, playing an important role in the regulation of a number of physiological processes. There are several subtypes of histamine receptors—H 1, H 2, H 3 and the recently discovered H 4. H 1 receptors exist on mast cells, basophils, enterochromaffin cells and in the central nervous system, being located postsynaptically. H 1 receptor antagonists, including classical antiallergy drugs, occasionally have been expected to induce convulsions in children and epileptics. The aim of this study was to evaluate the effects of astemizole-given intraperitoneally, singly or for 7 days on the anticonvulsant activity of antiepileptic drugs (AEDs) against maximal electroshock (MES)-induced convulsions in mice. The following AEDs were administered intraperitoneally: valproate magnesium, carbamazepine, diphenylhydantoin and phenobarbital. Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Brain and plasma levels of AEDs were measured by immunofluorescence. Astemizole (a single dose and following a 7-day treatment at 2–6 mg/kg) reduced the threshold for electroconvulsions, being without effect upon this parameter at lower doses. Astemizole (1 mg/kg) did not significantly alter the protective effect of AEDs against MES (after acute and 7-day administration). Also, acute astemizole (2 mg/kg) remained ineffective in this respect. Astemizole (2 mg/kg), following chronic administration, significantly reduced the protective efficacy of phenobarbital and diphenylhydantoin, reflected by an increase in their ED 50 values (50% effective dose necessary to protect 50% of animals tested against MES) from 21.1 to 34.0 mg/kg and from 10.4 to 19.2 mg/kg, respectively. Astemizole (2 mg/kg) did not alter the protective activity of the remaining AEDs. Moreover, astemizole (2 mg/kg) did not influence the free plasma levels and brain concentration of the studied AEDs. Also, this H 1 receptor antagonist did not impair long-term memory or motor coordination when given acutely. However, 7-day treatment with astemizole (2 mg/kg) significantly decreased TD 50 (50% toxic dose required to induce motor impairment in 50% of animals) value of phenobarbital, being without effect on carbamazepine, valproate and diphenylhydantoin in this respect. Similarly, phenobarbital and diphenylhydantoin, administered alone at their ED 50s against MES, or combined with astemizole, disturbed long-term memory in mice. The results of this study indicate that astemizole may need to be used with caution in epileptic patients.

Primary generalized epilepsy: a risk factor for seizures in labor and delivery?

Purpose: Women in the United States who have epilepsy give birth to about 20 000 newborns every year. Because seizures during late gestation and delivery may seriously affect the fetus, and because primary generalized tonic–clonic (GTC) seizures may occur during labor and delivery in 1–2% of women with epilepsy, we attempted to define the rate, risks, and causes of seizures during labor and delivery. Methods: To characterize seizures during labor and delivery, we retrospectively analyzed 89 consecutive pregnancies of women with epilepsy on antiepileptic drugs (AEDs). Six epileptologists in our group had treated these patients. We confirmed data and acquired new information by telephone for 83.1% of the pregnancies, and categorized the women as having primary generalized or partial epilepsy. Most of the patients (78%) were on monotherapy during pregnancy; 20% took two AEDs, and 3% took three AEDs during that period. Results: Seizures during labor and delivery occurred in 4/32 (12.5%) patients with primary generalized epilepsy, but in none of the 57 women with partial epilepsy ( P<0.05). None of the 38 patients with therapeutic AED levels before labor and delivery had seizures, compared to 3/37 (8.1%) of the subtherapeutic group. However, drug levels were taken at variable times in relation to delivery, limiting their value. Also, the levels sampled were both total and free levels; the latter would be more helpful to determine the adequacy of AED drug coverage. Conclusions: Maintaining therapeutic AED levels during the last trimester may help prevent seizures during labor and delivery, especially in women with generalized epilepsy. Women with epilepsy who had subtherapeutic AED levels and had been seizure-free may be at-risk for seizures during labor and delivery. Our sample was small, and a random sampling bias may have affected the results.

A Computer-Based Intervention for Improving the Appropriateness of Antiepileptic Drug Level Monitoring

We designed and implemented 2 automated, computerized screens for use at the time of antiepileptic drug (AED) test order entry to improve appropriateness by reminding physicians when a potentially redundant test was ordered and providing common indications for monitoring and pharmacokinetics of the specific AED. All computerized orders for inpatient serum AED levels during two 3-month periods were included in the study. During the 3-month period after implementation of the automated intervention, 13% of all AED tests ordered were canceled following computerized reminders. For orders appearing redundant, the cancellation rate was 27%. For nonredundant orders, 4% were canceled when information on specific AED monitoring and pharmacokinetics was provided. The cancellation rate was sustained after 4 years. There has been a 19.5% decrease in total AED testing volume since implementation of this intervention, despite a 19.3% increase in overall chemistry test volume. Inappropriateness owing to repeated testing before pharmacologic steady state was reached decreased from 54% of all AED orders to 14.6%. A simple, automated, activity-based intervention targeting a specific test-ordering behavior effectively reduced inappropriate laboratory testing. The sustained benefit supports the idea that computerized interventions may durably affect physician behavior. Computerized delivery of such evidence-based boundary guidelines can help narrow the gap between evidence and practice.

A computer-based intervention for improving the appropriateness of antiepileptic drug level monitoring.

We designed and implemented 2 automated, computerized screens for use at the time of antiepileptic drug (AED) test order entry to improve appropriateness by reminding physicians when a potentially redundant test was ordered and providing common indications for monitoring and pharmacokinetics of the specific AED. All computerized orders for inpatient serum AED levels during two 3-month periods were included in the study. During the 3-month period after implementation of the automated intervention, 13% of all AED tests ordered were canceled following computerized reminders. For orders appearing redundant, the cancellation rate was 27%. For nonredundant orders, 4% were canceled when information on specific AED monitoring and pharmacokinetics was provided. The cancellation rate was sustained after 4 years. There has been a 19.5% decrease in total AED testing volume since implementation of this intervention, despite a 19.3% increase in overall chemistry test volume. Inappropriateness owing to repeated testing before pharmacologic steady state was reached decreased from 54% of all AED orders to 14.6%. A simple, automated, activity-based intervention targeting a specific test-ordering behavior effectively reduced inappropriate laboratory testing. The sustained benefit supports the idea that computerized interventions may durably affect physician behavior. Computerized delivery of such evidence-based boundary guidelines can help narrow the gap between evidence and practice.

Major malformations in offspring of women with epilepsy.

The offspring of women with epilepsy are at an increased risk of major congenital malformations, but the impact of the various contributing factors remains unresolved. In 1980 through 1998, the authors prospectively followed up 970 pregnancies in women with epilepsy at a single maternity clinic. Of their 979 offspring, 740 were exposed to maternal antiepileptic drugs (AED) during the first trimester of pregnancy and 239 were not exposed. Maternal AED levels and serum folate concentrations were measured at the end of the first trimester. Logistic regression analysis was applied to identify factors associated with the occurrence of major malformations in the fetuses and newborns. Major malformations were detected in 28 fetuses (3.8%) exposed to maternal AED and in 2 (0.8%) not exposed (p = 0.02). After logistic regression analysis, the occurrence of major malformations was independently associated with use of carbamazepine (adjusted OR 2.5; 95% CI 1.0 to 6.0), use of valproate (4.1; 1.6 to 11), use of oxcarbazepine (10.8; 1.1 to 106), low serum folate concentration (5.8; 1.3 to 27), and low maternal level of education (3.0; 1.3 to 6.8). Major malformations were not associated with seizures during the first trimester (0.6; 0.1 to 2.9). Major malformations in the offspring of mothers with epilepsy are associated with use of AED during early pregnancy, and also with low serum folate concentrations and a low level of education.

Utility of antiepileptic drug monitoring in the pediatric emergency department.

Convulsive disorders are common in the pediatric age group, and measurement of serum concentration of an antiepileptic drug (AED) is frequently ordered for epileptic patients in the emergency department (ED). The objective of this study was to develop a better understanding of the indications for, and consequences of, monitoring AED serum concentrations in the pediatric ED. Charts of 116 patients who visited the ED and were tested for blood levels of AED were retrospectively reviewed. Main outcome measures were number and percentage of levels outside the therapeutic range, discontinuation of an AED or introduction of a new one, dosage modifications, and admission to hospital. Two pediatricians and a pediatric neurologist aware only of patients' age, weight, diagnosis, history, clinical presentation, and drug details reviewed each case and on the basis of predetermined criteria decided whether measurement of AED was indicated. Mean age (+/- SD) of the study population was 7 +/- 5 years (range, 2 months-17 years). Forty-two patients (36%) were on monotherapy, and 74 (64%) were on polytherapy. Sixty-eight patients (59%) presented with increased seizure frequency, 7 (6%) with status epilepticus, and 13 (11%) with suspected AED toxicity. The remainder of the children presented with problems unrelated to epilepsy. No significant difference was found between patients with AED levels within the therapeutic range and those with levels outside it in the proportion of children needing dosage change, change in medication, or hospital admission (P = 0.5, 0.8, and 0.8, respectively). None of the patients presenting with status epilepticus and only 15% of those with increased seizure activity had subtherapeutic levels. Review of the cases suggested that measuring serum AED level was not indicated in 57 (49.1%) patients. In the pediatric ED, abnormal AED levels do not correlate with clinical management. Before ordering tests, physicians should consider whether their results would alter patient treatment.