Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal

We studied the cognitive effects of antiepileptic drugs (AED), by investigating epileptic children who were seizure-free for at least 2 years and who had undergone fixed monotherapy. Seventy consecutive epileptic children (25 with carbamazepine (CBZ), 22 with phenobarbital (PB), and 23 with valproate (VPA)) were examined by Wechsler Intelligence Scale for Children-Revised (WISC-R) and auditory event-related potentials (P(300)) at three sessions: before AED reduction, then 1 and 7 months after complete withdrawal of treatment. There were no significant differences in IQ and subtests scores of WISC-R in any group at any of the three sessions. P(300) latencies were significantly increased in the children receiving PB but not in children receiving CBZ or VPA. P(300) amplitudes were increased but not significantly different among the three groups. These findings suggest that PB may affect cognitive function on children, but the changes of P(300) latencies may improve after discontinuation.     

Effects of Discontinuation of Phenytoin, Carbamazepine, and Valproate on Concomitant Antiepileptic Medication

We report a prospective, controlled study of the effects of the reduction and discontinuation of phenytoin (PHT) (22 patients), carbamazepine (CBZ) (23 patients), and valproate (VPA) (25 patients) with concomitant antiepileptic drugs (AEDs). The principal changes in the serum concentrations of concomitant AEDs were (a) phenobarbital (PB) concentrations decreased by a mean of 30% on discontinuation of PHT; (b) total CBZ concentrations increased by a mean of 48% and free CBZ concentrations increased by a mean of 30% on discontinuation of PHT, with no change in CBZ-10, 11-epoxide (CBZ-E) concentrations; (c) VPA concentrations increased by a mean of 19% on discontinuation of PHT; (d) VPA concentrations increased by a mean of 42% on discontinuation of CBZ; (e) ethosuximide (ESM) concentrations increased by a mean of 48% on discontinuation of CBZ; (f) PHT concentrations decreased by a mean of 26% on discontinuation of CBZ; (g) PHT free fraction decreased from a mean of 0.11 to 0.07 on discontinuation of VPA; and (h) the mean concentrations of total and free CBZ increased by a mean of 10 and 16%, respectively, on VPA discontinuation, with a concomitant mean 24% decrease in total CBZ-E and a 22% decrease in free CBZ-E. Apart from the decrease in PB concentrations on PHT discontinuation, all significant changes had occurred by 1 week after the end of AED discontinuation. The implication for clinical practice is that a serum AED concentration at this time reflects the new steady state. Free concentrations did not add any clinically useful information to that gained from analysis of total serum concentrations.     

Comparison of Antiepileptic Drugs on Cognitive Function in Newly Diagnosed Epileptic Children: A Psychometric and Neurophysiological Study

Summary: Using a randomized parallel group study design, we compared the cognitive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P₃₀₀) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P₃₀₀ latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P₃₀₀ amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P₃₀₀ may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.     

The effects on lipid and apolipoprotein serum levels of long-term carbamazepine, valproic acid and phenobarbital therapy in children with epilepsy

The aim of the present study was to assess the effect of long-term carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PB) treatment on serum lipids and apolipoproteins in epileptic children. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TGs) were measured and the LDL-C/HDL-C and TC/HDL-C ratios were calculated in 320 children and adolescents (129 receiving CBZ, 127 receiving VPA and 64 receiving PB) suffering from various types of epilepsy. Additionally, in a subgroup of 181 children (68 CBZ; 78 VPA; 35 PB) apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), HDL2-C and HDL3-C were measured and apoA-I/apoB and HDL2-C/HDL3-C ratios were calculated. Results of the measurements were compared with those of 169 age-and sex-matched healthy controls. None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. TC and LDL-C serum levels were high in children receiving CBZ or PB and low in those treated with VPA. Serum LDL-C level exceeded 130 mg/dl in 27.9% of CBZ-group, 31.8% of the subjects receiving PB, but only in 7% of those receiving VPA and in 11.8% of control group subjects. CBZ-treated children also showed high HDL-C and HDL3-C values. In the group receiving VPA, HDL2-C, HDL2-C/HDL3-C ratio and apo B were significantly lower than in the control group. Mean apoA-I levels were low in all treated groups: by contrast, in neither group did TGs, VLDL-C levels and TC/HDL-C or LDL-C/HDL-C ratios differ significantly from the corresponding control group. Our results suggest that the effects of long-term AED therapy on lipid profile and, particularly, on apolipoprotein serum levels increase risk of atherosclerosis-related disease. Moreover, these results confirm our previously reported increased risk in CBZ and PB-treated patients.     

Effects of antiepileptic drugs on delivery and early childhood--comparison among mono-therapies of valproic acid, phenytoin, carbamazepine and phenobarbital

The effects of antiepileptic drugs (AED) on infants during pregnancy and delivery were studied in a total of 82 epileptic mothers on various monotherapies; 29 cases receiving valproic acid (VPA), 20 receiving phenytoin (PHT), 18 on carbamazepine (CBZ) and 15 on phenobarbital (PB). While AED serum concentrations were low in most cases of VPA, PHT and PB except for one case of VPA which exceeded therapeutic limits, concentrations were within therapeutic levels in many cases of CBZ. Conclusion: When compared with normal controls, abnormal deliveries such as caesarian section were seen more frequently in epileptic mothers under AED treatment. In addition, infants in PB cases were shown to have significantly lower mean birth length, weight and head circumference, suggesting that PB may retard fetal growth. The incidence of malformation in cases of VPA, PHT, CBZ and PB, was 10.3%, 5.0%, 0% and 6.7%, respectively. There were five types of malformation: in VPA cases, spina bifida, Siamese twins and ventricular septal defect tended to be severe, while in PHT and PB cases, cor biloculare and hypospadias respectively were observed. In cases of VPA, serum levels in the umbilical cord were found to be 150% higher than those in the mother.     

Antiepileptic Drugs and Peripheral Nerve Function: A Multicenter Screening Investigation of 141 Patients with Chronic Treatment

Summary: One hundred forty-one adult patients treated for no less than 6 months with standard daily doses of the commonest antiepileptic drugs (AEDs) were recruited in five Italian centers and submitted to intensive clinical and electrophysiologic investigation to assess the effects of AEDs on peripheral nerves. Eighty percent of the patients were receiving monotherapy. Carbamazepine (CBZ) was the most common AED (51 cases), followed by phenytoin (PHT) (46), phenobarbital (PB) (42), and valproate (VPA) (25). Fifty-three percent of the patients had one or more symptoms of polyneuropathy (paresthesias being the most common complaint). The neurologic examination was abnormal in 32%. Electrophysiologic findings in two or more separate nerves were abnormal in 77 patients (54.6%); of these, 27 (19.1%) had abnormal neurologic findings and 21 (14.9%) also had symptoms of polyneuropathy. Sensory functions were most frequently impaired. Sural nerve biopsy was performed in 4 patients receiving monotherapy with CBZ, PHT, PB, and VPA. Except in patients receiving VPA (in whom no morphologic abnormalities were detected), mild predominantly axonal damage with secondary myelin changes was noted. A correlation was noted between polyneuropathy, age of the patient and, to a lesser extent, receipt of two or more AEDs.     

Profile of Antiepileptic Pharmacotherapy in a Tertiary Referral Center in South India: A Pharmacoepidemiologic and Pharmacoeconomic Study

Summary: Purpose: To study the current pharmacotherapy practices of epilepsy and its economics in a developing country by correlating the epidemiology and economics of antiepileptic drug (AED) treatment in general epilepsy care and comprehensive epilepsy care.
Methods: We compared the AED-use profiles, efficacy, and tolerability at entry and at last follow-up for 972 patients seen at a comprehensive epilepsy care program in South India from 1993 to 1995. The relative cost was expressed as the average percentage of the per capita gross national product (GNP/capita) each individual spent for AED treatment.
Results: At entry, 562 (57.8%) subjects were receiving poly-therapy; at last follow-up, 743 (76.4%) patients were receiving monotherapy, an increase of 34.3% in the use of monotherapy. One or more adverse drug reactions were reported by 28.6% of patients at entry and by 19.8% at last follow-up. The proportion of patients who were seizure free increased from 29.0 to 44.8%. Carbamazepine (CBZ) was the most frequently used AED, followed by diphenylhydantoin (DPH), valproate (VPA), and phenobarbitone (PB). The relative cost (% GNP/capita) for standard AEDs were as follows: PB, 4.4%; DPH, 7.1%; CBZ, 16.8%; and VPA, 29.5%. The average annual cost of AED treatment per patient in U.S. dollars was $64.32 at entry and $47.73 at last follow-up. Reduction in polytherapy resulted in the net annual saving of $16,128 ($16.59 per patient, or 5.4% GNP/capita).
Conclusions: The more frequent use of relatively expensive drugs like CBZ and VPA and the use of polytherapy—still quite prevalent in developing countries—has escalated the cost of AED therapy. Although in recent years AEDs have become more available in developing regions, primary and secondary care physicians have not been adequately educated about the current trends in the pharmacotherapy of epilepsy.     

Evaluation of bone mineral density using digital image processing in children receiving anticonvulsants

Bone mineral density (BMD) increases rapidly in a biphasic manner in childhood. During and after adolescence, BMD correlates more closely with bone age than chronological age. Digital image processing (DIP) allows the rapid assessment of BMD and bone age on one X-ray film. Herein, using DIP methods, the effects of various anticonvulsants on chronological and bone age were evaluated in 98 epilepsy patients (age range, 3-15 years) with no intellectual or motor disorders or diseases affecting bone metabolism. All patients were taking one or a combination of the following anticonvulsants: valproate sodium (VPA); carbamazepine (CBZ); and phenobarbital (PB). Bone maturation scores for radius-ulnar-short bones (RUS) were calculated using Tanner-Whitehouse 2 methods. Bone age was determined based on standard Japanese bone-maturation scores. In each patient, Z-scores for chronological and bone ages were calculated by subtracting standard BMD for gender and age from each BMD, then dividing the result by the standard deviation. The Z-score for each drug in relation to the administration period was analyzed using the Mann-Whitney test. For chronological age, significant differences in BMD were observed regarding the administration periods in children taking multiple drugs, but not in children on VPA, CBZ, or PB monotherapy. For bone age, no significant differences in BMD were observed regarding the administration periods for all drugs. Children taking multiple drugs showed a significant negative correlation between administration period and Z-scores for BMD calculated based on chronological age (Spearman rank correlation: - 0.457, p = 0.008), but not bone age. Among children receiving long-term VPA administration, bone age was delayed approximately 1 year, and bone maturation may have been delayed. No delay in bone age was noted among children receiving long-term administration of multiple drugs, suggesting that these anticonvulsants do not influence bone maturity. These findings indicate that bone age should be considered when assessing BMD.     

Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism

PURPOSE: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB). METHODS: We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIU/L in our study) and <6 mIU/L; II, TSH between 6 and 12 mIU/L; and III, TSH >12 mIU/L. RESULTS: In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ- and VPA-treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal-range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism. CONCLUSIONS: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.     

Discontinuation of Phenytoin, Carbamazepine, and Valproate in Patients with Active Epilepsy

The effects of discontinuing individual antiepileptic drugs (AEDs) in patients with active epilepsy who are receiving combination therapy have not been studied systematically. We report a double-blind, prospective study of discontinuation of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) in 70 patients with chronic active epilepsy. Each drug discontinuation was randomized to one of two relatively fast rates of reduction, and a control group of 25 patients continued with stable therapy. Patients who had CBZ removed had a significant increase in seizures that was maintained for 4 weeks after the end of drug reduction, and 10 of these 23 patients had to restart therapy with CBZ. There was no significant change in seizure numbers in the other groups. Two patients discontinued from VPA had to restart the drug; none had to restart PHT. The optimal rates of reduction of CBZ remain uncertain. There was no evidence for a clinically or temporally distinct burst of "discontinuation seizures" in any group. Any marked increase in seizures always resolved on reintroduction of the discontinued drug.     

Clinical Side Effects of Phenobarbital, Primidone, Phenytoin, Carbamazepine, and Valproate During Monotherapy in Children

The rate of onset of side effects was examined in 392 pediatric outpatients who received long-term monotherapy with phenobarbital (PB), primidone (PRM), phenytoin (PHT), carbamazepine (CBZ), or valproate (VPA) for epilepsy or febrile convulsions. The severity of side effects (based on need to alter treatment), the nature of each drug's most common side effects, and the doses and plasma levels of occurrence were recorded. Our results show that usually accepted therapeutic ranges are well tolerated. Indeed, although some form of side effect occurred in 50% of patients, treatment had to be changed in only 18% and the drug had to be stopped in only 7%. In decreasing order, the rates for side effects were PHT (71%) greater than PB (64%) greater than CBZ (43%) greater than VPA (43%) greater than PRM (29%). Serious side effects requiring withdrawal of treatment occurred at the following rates: PHT (10%) greater than VPA (8%) greater than PRM (8%) greater than PB (4%) greater than CBZ (3%). Among our patients, the best tolerated antiepileptic drug (AED) was CBZ, and the least tolerated was PHT. Behavioral disorders were most common with PB, neurologic disorders with PHT, digestive tract disorders with VPA, and gingival hyperplasia and hirsutism with PHT. Behavioral disorders involving excitement seen with PB and PRM occurred most commonly at low plasma levels. Behavioral disorders involving depression seen with PB and VPA, those involving excitement seen with PHT and VPA, and digestive disorders seen with VPA occurred particularly when plasma levels were high.     

Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy

PURPOSE: Pregabalin (PGB) is an alpha2-delta ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures. METHODS: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open-label, multiple-dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ). RESULTS: Trough steady-state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB-AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug-drug interactions.     

Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy

PURPOSE: All major antiepileptic drugs (AEDs) have been reported to be associated with cognitive side effects. Uncertainty exists regarding the degree of cognitive effects, primarily because many studies do not adhere to basic standards of methodology and design. The aim of this study was to assess the effect of discontinuation of AEDs in patients receiving monotherapy on measures of attention, reaction time, and speed of information processing. METHODS: The 150 subjects who had been seizure free>2 years on drug monotherapy went through a randomized, double-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after discontinuation. RESULTS: The major finding in this study is that discontinuation of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the two groups on these tasks was between 24 to 43 ms. Simple tasks of attention and reaction time revealed no significant differences between the discontinuation group and the nondiscontinuation group. Most of the subjects in the study were medicated with carbamazepine (CBZ) and valproate (VPA). The outcome of discontinuation of CBZ was similar to the outcome for the total study population, whereas withdrawal of VPA revealed only a nonsignificant tendency in the same direction. CONCLUSIONS: The results suggest that seizure-free epilepsy patients receiving monotherapy can obtain improvement in cognitive function if they discontinue AED treatment.     

Lack of Interaction of Gabapentin with Carbamazepine or Valproate

Summary: Gabapentin (GBP) studies were conducted in patients with epilepsy receiving carbamazepine (CBZ, n= 12) or valproate (VPA, n = 14) monotherapy. The effects of GBP coadministration on steady-state CBZ or VPA concentrations and of these antiepileptic drugs (AEDs) on GBP pharmacokinetics were investigated. GBP (400 mg) was coadministered every 8 h for 3% days with CBZ or for 5 1/3 days with VPA. GBP was well tolerated. Mean steady-state plasma CBZ/CBZ-10, ll-epoxide (CBZ-E) and serum VPA concentrations before, during, and after GBP administration were not significantly different. Mean steady-state GBP pharmacokinetic parameters during CBZ or VPA coadministration were similar to steady-state parameters reported in healthy subjects. Thus, no pharmacokinetic interaction exists between CBZ or VPA and GBP. No dosage adjustment is necessary when GBP and CBZ or VPA are coadministered.     

Thyroid Function with Antiepileptic Drugs

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of valproic acid,carbamazepine, and phenobarbitone on the fatty acid composition of erythrocyte membranes in children

PURPOSE: To investigate a possible relation between antiepileptic drugs (AEDs) and the fatty acid composition of membranes. METHODS: Fatty acid (FA) composition of erythrocytes was studied in children with epilepsy receiving AED monotherapy. Children taking valproate (VPA, n = 28), carbamazepine (CBZ, n = 17), or phenobarbitone (PB, n = 14) were compared with healthy controls (n = 25). FAs were measured by capillary-gas chromatography (GC-FID). RESULTS: Significant changes (p < 0.05) in the FA composition of membranes were found. In children treated with VPA, C13:0 was decreased (8.2 +/- 2% vs. 10.7 +/- 4% in controls) and C14:0 increased (1.4 +/- 0.5% vs.1 +/- 0.5% in controls). C17:0 again was reduced (9.9 +/- 4% vs. 13.2 +/- 6% in controls), whereas the long-chained acids were enhanced: C18:2n-6 (6 +/- 2.4% vs. 3.9 +/- 2.5% in controls), and C20:4n-6 (1.9 +/- 1.7% vs. 1.4 +/- 0.5% in controls). The nonidentified FAs also increased with VPA therapy: 2.5 +/- 0.8% versus 1.7 +/- 0.9% in controls. Children treated with CBZ showed only minimal changes of FA composition: C13:0 was decreased compared with controls (8 +/- 2% vs. 10.7 +/- 4%). No changes were seen in patients taking PB. The mean corpuscular volume (MCV) showed important differences between the study groups: MCV was 84.7 +/- 6.0 fl during VPA therapy (p < 0.001) and 85.7 +/- 4.1 fl with CBZ (p < 0.001). During PB, the MCV increased to 82.87 +/- 3.29 fl compared with controls (78.73 +/- 4.92 fl; p < 0.01). CONCLUSIONS: VPA therapy is associated with changes of the FA composition of membranes, which is not the case with PB therapy. The implications of this finding remain to be established.     

Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

Purpose: Long‐term therapy with antiepileptic drugs (AEDs) has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. We compared the long‐term effects of monotherapy using different categories of AEDs on markers of vascular risk and the atherosclerotic process. Methods: One hundred sixty adult patients who were receiving AED monotherapy, including two enzyme‐inducers (carbamazepine, CBZ; and phenytoin, PHT), an enzyme‐inhibitor (valproic acid, VPA), and a noninducer (lamotrigine, LTG) for more than 2 years, and 60 controls were enrolled in this study. All study participants received measurement of common carotid artery (CCA) intima media thickness (IMT) by B‐mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index, and serum lipid profile or levels of total homocysteine (tHcy), folate, uric acid, fasting blood sugar, high sensitivity C‐reactive protein (hs‐CRP), or thiobarbituric acid reactive substances (TBARS). Key Findings: Long‐term monotherapy with older‐generation AEDs, including CBZ, PHT, and VPA, caused significantly increased CCA IMT in patients with epilepsy. After adjustment for the confounding effects of age and gender, the CCA IMT was found to be positively correlated with the duration of AED therapy. Patients with epilepsy who were taking enzyme‐inducing AED monotherapy (CBZ, PHT) manifested disturbances of cholesterol, tHcy or folate metabolism, and elevation of the inflammation marker, hs‐CRP. On the other hand, patients on enzyme‐inhibiting AED monotherapy (VPA) exhibited an increase in the levels of uric acid and tHcy, and elevation of the oxidative marker, TBARS. However, no significant alterations in the markers of vascular risk or CCA IMT were observed in patients who received long‐term LTG monotherapy. Significance: Patients with epilepsy who were receiving long‐term monotherapy with CBZ, PHT, or VPA exhibited altered circulatory markers of vascular risk that may contribute to the acceleration of the atherosclerotic process, which is significantly associated the duration of AED monotherapy. This information offers a guide for the choice of drug in patients with epilepsy who require long‐term AED therapy, particularly in aged and high‐risk individuals.     

Comparison of AccuLevel and TDx: Evaluation of On-Site Monitoring of Antiepileptic Drugs

Therapeutic drug monitoring, an important aid in antiepileptic drug (AED) therapy, has a lag time before results are obtained from clinical laboratories. The AccuLevel test is an enzyme immunochromatographic method for quantitative measurement of AEDs including phenobarbital (PB), phenytoin (PHT), and carbamazepine (CBZ), with results available within 20 min. A comparison between AccuLevel and TDx, (fluorescence polarization immunoassay) was conducted in 233 paired blood samples from patients with AED therapy, including 12 Eskimo children receiving treatment in Greenland. Forty-five blood samples were analyzed for PB, 80 for PHT, and 108 for CBZ. Linear regression analysis showed good agreement between the two methods (r = 0.951, 0.958, and 0.945, respectively). The test is easy to perform, but care must be taken to follow the correct procedure, or inaccuracies will result. That happened in some of our results. A reduction in lag time, using on-site drug monitoring, was demonstrated. The AccuLevel is a rapid, accurate, and convenient method for use in AED monitoring.