Search

Background: The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC. Patients and methods: This was an open‐labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs. Results: Fifteen (15.2%) patients [CBZ‐ 4(8.2%); LEV‐ 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug‐related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow‐up. Conclusion: CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group. [ABSTRACT FROM AUTHOR]

Objective: The study is aimed at comparing effects of older drugs like carbamazepine (CBZ) and newer agent like levetiracetam (LEV) on polycystic ovarian syndrome (PCOS) in women with epilepsy (WWE). Methods: An interviewer‐based questionnaire was used to obtain relevant clinical information from 50 WWE on CBZ and LEV monotherapy, respectively, and 50 age‐matched controls. The diagnosis of epilepsy was clinical with electroencephalographic features taken into consideration and the seizures classified using the 2017 International League Against Epilepsy classification. The diagnosis of PCOS was based on the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Results: The frequency of PCOS and its subcomponent were higher among WWE compare to controls. PCOS was present in 22 (44%) of LEV group compare to 8 (16%) CBZ group. The frequency of its subcomponent was higher among those on LEV except for comparable effect with regard to oligomenorrhea. The levels of the sex steroid hormone were comparable in both groups of WWE except luteal phase luteinizing hormone, which was lower among the LEV group (P.001). The follicular phase estradiol level was lower (P.021), and follicle‐stimulating hormone level was about 2‐fold higher (P.03) among WWE compare to controls. The mean value testosterone was significantly lower among controls compared to WWE. Conclusions: The increased frequency of PCOS and its subcomponent and the unsatisfactory effect of LEV compared to CBZ on reproductive endocrine function underscore the need for routine reproductive endocrine evaluation to improve overall quality of life. [ABSTRACT FROM AUTHOR]

Objectives: To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient‐recognized depression during pregnancy in women with epilepsy. Materials and Methods: Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end. Results: Patient‐recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure‐affected than in seizure‐free pregnancies (5.67% vs 6.41%), though higher in AED‐treated than AED‐untreated pregnancies (6.24% vs 5.26%; RR = 1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient‐recognized depression occurring during pregnancy and topiramate dosage with an increasing rate. Conclusions: Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the time course of changes in perampanel levels when co‐administered with carbamazepine, and following carbamazepine discontinuation, using a physiologically based pharmacokinetic (PBPK) model. Methods: The PBPK model was developed, verified using clinical PK data, and used to simulate the effect of abrupt discontinuation and down‐titration (75 mg twice daily [bid]/wk) of co‐administered carbamazepine 300 mg bid on the PK of perampanel once daily (qd). Perampanel dose tapering (8‐4 mg) and up‐titration (2‐6 mg) were simulated during abrupt carbamazepine 300 mg bid discontinuation to identify a titration schedule that minimizes changes in perampanel plasma concentrations. Results: The PBPK model accurately reproduced perampanel plasma concentration‐time profiles from clinical studies in single‐ and multiple‐dose regimen simulations, including multiple‐dose carbamazepine co‐administration. The time course of return to pre‐induced perampanel levels occurred more slowly following carbamazepine down‐titration (~48 days after first down‐titration) vs abrupt discontinuation (~25 days). Perampanel dose tapering (8‐4 mg) at abrupt carbamazepine discontinuation produced minimal changes in steady‐state concentrations, which returned to the levels observed during carbamazepine co‐administration in ~15 days from the time of carbamazepine discontinuation. When perampanel was up‐titrated in the presence of carbamazepine, return to steady state occurred more slowly when carbamazepine was down‐titrated weekly (~45 days) vs abrupt discontinuation (~24 days). Conclusion: This PBPK model simulated and predicted optimal perampanel dose tapering and up‐titration schedules for maintaining perampanel levels during conversion to monotherapy. These results may guide physicians when managing conversion from perampanel polytherapy with concomitant enzyme‐inducing anti‐seizure medications to monotherapy. [ABSTRACT FROM AUTHOR]

The dibenzazepines particularly carbamazepine are associated with known adverse effects (AEs) and drug to drug interactions. Eslicarbazepine acetate (ESL) is structurally distinct from other members of the dibenzazepine family and has the advantage of once daily dosing. Observational and trial data report successful switching from older dibenzazepines to ESL. The evidence base for doing so is unclear and not standardized. This is a literature review following the PRISMA scoping guidelines identifying the evidence of switching dibenzazepines. Transition methods, ratios, tolerance to change, adverse effects and retention post‐change were evaluated. Study quality was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. Seven studies investigated the outcome of transition between carbamazepine and or oxcarbazepine to ESL, with specific data on the transition dose ratio and scheduling. The available data suggest that the overnight transition between oxcarbazepine and ESL in a 1:1 ratio (most common) is generally well tolerated with high retention rates. The transition showed improvement in adverse events associated with oxcarbazepine across a variety of domains. Almost 60% transitioned because of adverse events experienced no further symptoms at 12 months. There is less data on the transition from carbamazepine to ESL. The evidence available suggests an overnight transition in the ratio of 1:1.3‐1.5. The retention rate following transition from carbamazepine to ESL was 69% (follow‐up of 4 months) with almost half of those transitioned because of adverse events experiencing no further symptoms. There is Grade C evidence available to help guide clinicians in the transition. [ABSTRACT FROM AUTHOR]

Objective: Studies in children have shown an increased frequency of central hypothyroidism (CH) with long‐term use of antiepileptic drugs (AEDs). The aim of this study was to search for CH in adults treated with AEDs and find whether the type of AEDs used matters. Materials and methods: Adult epileptic patients treated at the neurology outpatient clinic at Landspitali University Hospital (LSH) from 1998 to 2011 were included. Patients were invited for a blood test if serum levels for TSH (s‐TSH) or free‐T4 (s‐fT4) had not already been obtained. CH was defined as s‐fT4 below the reference range (12‐22 pmol/L) and normal s‐TSH levels (0.30‐4.20 mIU/L). Data were analyzed using logistic regression and Mann‐Whitney test. Results: We identified 165 patients (92 women), mean age 45.6 (±15.5, range: 20‐92) years. The mean s‐fT4‐level in our group was 14.2 (±2.9, range: 8.1‐24.4) pmol/L compared with 16.9 (±6.1) pmol/L in a sample of 13248 measurements at LSH during one year (LSH‐group) (P < 0.001). The difference in s‐fT4‐level between men and the LSH‐group was significant and also for women (P < 0.001 and P < 0.001, respectively). Thirty‐five patients (21%) had CH. A significant association with the use of carbamazepine or oxcarbazepine was found, odds ratio for women 15.0 (95% CI: 4.6‐49.5) and 1.8 (95% CI: 0.4‐8.3) for men. Conclusion: 21% of patients treated with AEDs had CH, more often patients taking carbamazepine or oxacarbazepine, and more often women. The s‐fT4‐level was lower among patients treated with AEDs. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the effect of carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on sexual functions, sex hormones, and semen analysis and quality in male patients with epilepsy. Methods: A total of 59 male patients with epilepsy, of which 30 were on VPA monotherapy and 29 were on CBZ monotherapy, were included in the study between January 2015 and March 2016. A control group was established with 30 healthy males. Luteinizing hormone (LH), follicle‐stimulating hormone (FSH), prolactin (PRL), free testosterone (fT), estradiol (E2), sex hormone‐binding globulin (SHBG) levels and bioactive testosterone (BAT)/bioactive estradiol (BAE), and BAT/LH ratio were studied in groups. All groups received semen analysis and International Index of Erectile Function Scale (IIEF‐5) test for erectile dysfunction. Results: E2 and DHEAS levels were higher in VPA and CBZ groups compared to control group (P < .001, P = .014). The decrease in fT levels in the VPA group was statistically significant (P = .038). No significant difference was detected in levels of SHBG, LH, and FSH (P > .05). BAT/BAE ratios were low both in VPA and CBZ groups (P < .001; P < .001), while BAT/LH ratios were low only in CBZ group (P = .033). In semen analysis, semen volume and number of normal sperms were found to be significantly lower in patients receiving antiepileptic drugs compared to control group (P < .05). There were no differences between the groups in rates of abnormal sperm morphology. IIEF‐5 scores were found to be significantly lower in VPA and CBZ groups (P < .001). Conclusion: VPA or CBZ therapy may lead to dysregulation of sex hormones, sexual dysfunction, and alterations in semen analysis in male patients with epilepsy. This must be considered for the selection of antiepileptic drugs in young male patients. [ABSTRACT FROM AUTHOR]

Objective To clarify whether anti-epileptic drug exposure during pregnancy is associated with an increased risk of intrauterine foetal death. Methods Analysis of data from 2064 pregnancies with known outcomes included in the Australian Register of Antiepileptic Drugs in Pregnancy, 170 of the pregnancies being unexposed to the drugs in at least the first half of pregnancy. Results The relative risk (6.46; 95% C.I. 0.90, 46.22) of intrauterine death appeared higher, though not statistically significantly higher, in drug-exposed pregnancies compared with unexposed ones (3.44% vs 0.59%). There was no statistically significantly increased hazard associated with AED polytherapy as compared with monotherapy. Logistic regression analysis showed a statistically significantly increased and dose-related hazard of intrauterine death in relation to carbamazepine exposure. Conclusions Intrauterine exposure to anti-epileptic drugs, particularly carbamazepine, may be associated with an increased risk of foetal death during pregnancy. [ABSTRACT FROM AUTHOR]

The authors have mentioned most adverse effects of CBZ were minor, but 3 patients had to discontinue the medication due to rash, making the adverse effects severe in grading. Keywords: antiepileptic drugs; antiseizure medications; epilepsy; neurocysticercosis EN antiepileptic drugs antiseizure medications epilepsy neurocysticercosis 484 485 2 03/11/22 20220401 NES 220401 We read with interest the recent article titled "Carbamazepine versus levetiracetam in epilepsy due to neurocysticercosis" by Santhosh et al.1 The authors have concluded that carbamazepine (CBZ) and levetiracetam (LEV) could be used as alternatives in newly diagnosed patients of neurocysticercosis (NCC) at the behest of minor side effects in the CBZ group. [Extracted from the article]

Objective To ascertain efficacy and tolerability of carbamazepine ( CBZ), sodium valproate ( VPA), lamotrigine ( LTG) and levetiracetam ( LEV) using the UKAED register (). Methods Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV (n=72) and healthy control subjects ( CTR) on no medication (n=51) were extracted. All patients had anonymously provided information on seizure type and frequency and completed the Liverpool Adverse Event Profile ( LAEP). Results The number of seizure-free patients in the last 4 weeks was overall CBZ/ VPA/ LTG/ LEV=60%/79%/67%/67%, for generalized epilepsy was CBZ/ VPA/ LTG/ LEV=67%/89%/65%/94%, and for localization-related epilepsy was CBZ/ VPA/ LTG/ LEV=59%/71%/67%/57%. Mean LAEP scores were CBZ/ VPA/ LTG/ LEV/ CTR=42.21/39.66/39.86/43.01/29.69. The mean LAEP was significantly higher in patients reporting depression and in patients with active epilepsy than in patients without depression and remission. Central nervous system ( CNS) adverse effects including memory problems, difficulty concentrating, depression, unsteadiness, restlessness, feelings of anger, shaky hands and dizziness were significantly more frequent in CBZ, VPA, LTG and LEV than in CTR. The feeling of anger was significantly more frequent in LEV, and depression was significantly more frequent in CBZ compared to the other drugs. Conclusion In this Internet-based register of self-reported efficacy and tolerability, CBZ, VPA, LTG and LEV were similar. Self-reported CNS adverse effects were significantly more frequent than in controls. In addition, anger was associated with LEV and depression with CBZ. Confounding factors were depression and uncontrolled epilepsy. [ABSTRACT FROM AUTHOR]

Objective Patients treated with carbamazepine ( CBZ) have increased serum levels of total cholesterol ( TC), high-density lipoproteins ( HDL), and low-density lipoproteins ( LDL). We aimed to investigate whether these changes of serum lipids are reversible after CBZ withdrawal. Material and methods We used a prospective, randomized double-blinded design. A total of 160 patients who had been seizure free on anti-epileptic drug monotherapy for more than 2 years were included and randomized to withdrawal or not. The intervention was completed by 150 (80 females, 53%) patients. Serum samples from before and 4 months after completed withdrawal or no withdrawal were obtained from 130 patients (63 females, 48%). Of these, 84 were treated with CBZ, 28 with valproate, nine with phenytoin, four with phenobarbital, and five with lamotrigine. Of the patients who had been treated with CBZ, 47 were randomized to the withdrawal group, and 37 were randomized to the non-withdrawal group. Results Among the CBZ-treated patients, a significant decrease in serum levels of TC, LDL, and apolipoprotein B (ApoB) were found in the withdrawal group compared with the non-withdrawal group. Mean differences in change were as follows: TC 0.68 mmol/l ( P = 0.005, CL - 1.15 to −0.21); LDL - 0.67 mmol/l ( P = 0.001, CL - 1.03 to −0.29); ApoB - 0.13 g/l ( P = 0.02, CL - 0.23 to −0.03). No significant changes in HDL, apolipoprotein A, and C-reactive protein were detected. Conclusion Our results indicate that CBZ may have unfavorable effects on serum levels of TC, LDL, and ApoB. However, these changes seem to be reversible even after years of treatment. [ABSTRACT FROM AUTHOR]

In neurological malignancies, antiepileptic drugs (AEDs) are frequently used to control the seizure activity that accompanies the disorder. There is a growing body of evidence on the importance of AED selection for reasons other than pharmacokinetics (PK) properties. Epigenetic modifications may occur in glioblastomas, such as changes in gene methylation and histone acetylation states. Secondary mechanisms of AED drug action which impact these epigenetic modifications could play a significant role in patient survival outcomes. Both valproic acid (VPA) and carbamazepine have histone deacetylase (HDAC) inhibitory activities, and levetiracetam and VPA reduce the activity of O6-methylguanine-DNA methyltransferase (MGMT), a DNA-repair molecule implicated in resistance to alkylating agents used for chemotherapy. The use of AEDs for purposes other than seizure prophylaxis and their selection based on non-PK properties present a potential paradigm shift in the field of neuro-oncology. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to investigate immunoglobulin levels in patients with epilepsy using the antiepileptic drugs (AED) levetiracetam (LEV), carbamazepine (CBZ), or lamotrigine (LTG). Methods: A total of 211 patients and 80 controls (age: 18–45 years) of both genders were included. The patients had been treated with either LEV (n = 47), CBZ (n = 90), or LTG (n = 74) monotherapy for at least 6 months. Total concentrations of immunoglobulin G (IgG), IgG subclasses (IgG1, IgG2, IgG3, and IgG4), immunoglobulin A (IgA), and immunoglobulin M (IgM) were measured. Smoking, drinking habits, and physical activity were recorded, and body mass index (BMI) was calculated. Results: A significantly lower total IgG and IgG1 was found in both men and women treated with LTG and in men on CBZ. IgG2 and IgG4 were also lower in LTG‐treated women, and IgA and IgM were lower in LTG‐treated men. Patients treated with LEV did not differ from the control group. Conclusions: Low levels of immunoglobulins were found in patients with epilepsy treated with LTG or CBZ. As our group of patients consisted of otherwise healthy young adults, one should be especially aware of a possible effect of AEDs on immunoglobulin levels when treating selected patient groups, for example immunocompromised patients. Immunoglobulin concentrations should be measured in patients treated with LTG or CBZ who experience recurrent infections, and a change in medication should be considered. [ABSTRACT FROM AUTHOR]

Shirzadi M, Alvestad S, Hovdal H, Espeset K, Lydersen S, Brodtkorb E. Comparison of carbamazepine rash in multiple sclerosis and epilepsy. Acta Neurol Scand: 2012: 125: 60-63. © 2011 John Wiley & Sons A/S. Objectives - Studies on the comorbidity of multiple sclerosis (MS) and allergic disorders have shown conflicting results. Carbamazepine (CBZ) is widely used in MS to control pain. We have compared the incidence of rash from CBZ use in MS and epilepsy. Materials and Methods - Consecutive adult patients with MS and epilepsy were studied retrospectively. A detailed survey of medical records concerning CBZ treatment was performed. Results - A total of 495 patients with epilepsy and 442 patients with MS were included. Sixty-five per cent of patients with epilepsy and 20% of patients with MS had used CBZ. In CBZ-exposed patients, rash occurred in 15/89 (17%) in MS and in 43/323 (13%) in epilepsy, a difference which was not significant. Women below 50 years experienced more skin reactions than older women and men. The unadjusted odds ratio (OR) for rash in the MS vs epilepsy group was 1.32 (CI 0.70-2.51, P = 0.40). Adjusting groups for gender and age reduced the OR to 1.11 (CI 0.56-2.19, P = 0.76). Conclusion - Compared with epilepsy, which is only rarely caused by immunological mechanisms, the autoimmune disorder MS was not associated with a different occurrence of CBZ skin reactions. The trend towards an increased occurrence of rashes in MS can partly be explained by a higher predisposition to CBZ rash in women of fertile age. [ABSTRACT FROM AUTHOR]

Wieshmann UC, Tan GM, Baker G. Self-reported symptoms in patients on antiepileptic drugs in monotherapy. Acta Neurol Scand: 2011: 124: 355-358. © 2011 John Wiley & Sons A/S. Objective - To ascertain the frequency of self-reported symptoms in patients taking antiepileptic drugs (AED). Methods - We included patients on carbamazepine (CBZ) n = 36, valproate (VPA) n = 21, levetiracetam (LEV) n = 12, phenytoin (PHT) n = 11, lamotrigine (LTG) n = 20, patients not taking anticonvulsive drugs n = 19, and healthy control subjects (CTRL) n = 41 to complete the Liverpool Adverse Event Profile (LAEP). Results - The mean LAEP scores were CBZ/PHT/LEV/VPA/LTG/noAED/CTRL = 44.97/42.00/41.00/40.33/32.42/42.00/30.80. LEV scored overall in the same range as the older AED but had a different adverse effect profile with self-reported anger (33%) and shaky hands (42%) particularly frequent. Patients with depression or uncontrolled epilepsy had significantly higher LAEP scores than patients without depression or uncontrolled epilepsy. Conclusion - Our unblinded observational study of self-reported symptoms suggested LTG was overall the drug with the least self-reported symptoms. Larger studies are needed to determine whether this was a truly significant difference. LEV had a different side effect profile to older AED. Confounding factors were depression and uncontrolled epilepsy. This observation should be further tested with randomized studies. [ABSTRACT FROM AUTHOR]

Hessen E, Lossius MI, Gjerstad L. Improvement in verbal memory after withdrawal of carbamazepine and valproate in patients with well-controlled epilepsy: A randomized, double-blind study. Acta Neurol Scand: 2011: 123: 385-389. © 2010 John Wiley & Sons A/S. For most major antiepileptic drugs, neuropsychological side effects have been reported. Healthy volunteer studies have found that both carbamazepine and valproate impair aspects of verbal memory. The aim of this study was to assess the effects of carbamazepine and valproate on verbal memory, in a well-controlled epilepsy population. This was carried out with a randomized, double-blind and placebo-controlled study of anticonvulsant withdrawal in patients receiving monotherapy. In the carbamazepine group (n = 92), withdrawal significantly improved recall after 30 min (P = 0.03). In the valproate group (n = 32), withdrawal significantly improved performance of immediate word span (P = 0.04). Withdrawal was randomized to placebo, but the choice of medication was not randomized to placebo. This means that the shown differences in neuropsychological outcome cannot with full certainty be attributed to either antiepileptic drug. The improvement of memory, after both carbamazepine and valproate withdrawal, was slight, and the impact on daily life function is uncertain. [ABSTRACT FROM AUTHOR]

Objective – We aimed to compare the effects of antiepileptic drugs and provide findings of peripheral nerve impairment using standard electrophysiological techniques. Materials and methods – Young adult outpatients with epilepsy on monotherapy for no less than 6 months with carbamazepine (CBZ), valproic acid (VPA), oxcarbazepine (OXC) and topiramate (TPM) were examined. Patients who had any other disease that could effect nerve conduction studies and who had neuropathic symptoms were excluded. Results – Each group contained 15 patients and 20 healthy subjects were examined as the control group. Prolonged latency of median sensory nerve ( P = 0.004), ulnar sensory nerve ( P = 0.01) and sural nerve ( P = 0.003) with a diminished nerve conduction velocity was observed in the CBZ group ( P = 0.014, P = 0.002, P = 0.025, respectively). No correlation was found between VPA, OXC and TPM and the nerve conduction studies ( P > 0.05). Conclusions – Valproic acid, oxcarbazepine and topiramate don’t have effects on nerve conduction studies. Mild electrophysiological changes contribute to carbamazepine therapy. [ABSTRACT FROM AUTHOR]

Background – Understanding how antiepileptic (AED) monotherapy influences normative test scores is of importance in the clinic for correct interpretation of neuropsychological profiles. Previous studies have primarily reported minor influence on neuropsychological raw scores, and the clinical relevance of these findings is unclear. Aim of the study –To obtain a clinical valid answer to this question, we analysed changes in T-scores after AED withdrawal in a large group of well-controlled epilepsy patients, for tests previously shown to be sensitive to AED withdrawal. Methods –We report outcomes on measures of choice reaction time from the California Computerized Assessment Package, on the Controlled Oral Word Association Test and on the Stroop Color-Word Interference Test. Results –Significantly improved T-scores were revealed after AED withdrawal on five of the six tests of executive functions with mean improvement of 5 T-scores. Comparable results were achieved in the subgroup taking carbamazepine, with a mean improvement of 6.2 T-scores. Conclusion –The present results suggest that T-scores for computerized tests of choice reaction time and tests of verbal fluency and response inhibition may be significantly impaired as a consequence of AED monotherapy, and that careful interpretation of these scores is required in diagnostic assessment of patients receiving AED monotherapy. [ABSTRACT FROM AUTHOR]

Introduction – Epilepsy is the most common non-infectious neurologic disease in developing countries such as Africa, including Nigeria. This study was designed to assess the intellectual performance of patients with epilepsy (PWE) in Nigeria hoping that the result will serve as the basis for educational, vocational, and social counseling. Methods – Forty-one PWE were studied along with 41 age-, sex- and education-matched healthy controls. A questionnaire was developed and applied to all subjects and history was taken from patients and eyewitness. The intellectual function of each subject was assessed with the aid of Wechsler Adult Intelligence Scale adapted for Nigerians. All patients subsequently had electroencephalography (EEG) performed and the EEG findings were noted. SPSS statistical package was used to analyze the data. Result – The PWE performed poorly on the verbal IQ, performance IQ, and full scale IQ scores when compared with controls ( P < 0.05) and 20% of PWE had mental retardation. Long duration of epilepsy, long duration of antiepileptic drug therapy, younger age at onset of epilepsy, increased frequency of seizures, and low educational status were found to have negative impacts on intellectual performance in PWE ( P < 0.05) while seizure types and type of antiepileptic drugs (carbamazepine or phenytoin) did not influence intellectual performance. Conclusion – This study shows that PWE had significant intellectual impairment when compared with controls. In addition, long duration of epilepsy, long duration of AED therapy, earlier age of onset, increased seizure frequency, and low educational status had a negative impact on intellectual functioning in PWE. [ABSTRACT FROM AUTHOR]

Objective – To explore effectiveness, tolerability and changes in quality of life in patients with epilepsy converting to topiramate (TPM) from carbamazepine (CBZ) or oxcarbazepine (OXC) due to insufficient effectiveness and/or tolerability. Methods – A multicenter, open-label, non-interventional trial was used to examine patients (≥ 12 years) with epilepsy, changing to TPM monotherapy from baseline mono- or combination therapy with CBZ or OXC. TPM was added to the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1–2 weeks, until a final dose between 50 and 200 mg/day was reached. On the basis of clinical judgment, the treating physician decided whether or not the existing AED treatment with CBZ or OXC could then be withdrawn. Type and number of seizures, preferred TPM dose, quality of life (QOLIE-10 questionnaire), subjective perception of improvement and adverse events (AE) were documented. Results – 140 patients (53.5% women, mean age 47 years) decided to switch to TPM due to insufficient effectiveness (75% of patients) and/or poor tolerability (80%) of the CBZ/OXC treatment. Average duration of follow-up was 24 weeks with an overall discontinuation rate of 19.3%, mainly due to AEs (12.1%). At study endpoint, the intended shift to TPM monotherapy was achieved in 73% of patients at a median TPM dose of 100 mg/day. A seizure reduction of ≥ 50% was achieved in 91% of patients in the last scheduled period (weeks 12–26); 62% of patients entering that period remained seizure free. Quality of life at endpoint improved significantly when compared with baseline for all domains of QOLIE-10 ( P < 0.001). Most frequent AEs (reported by ≥ 5% of patients) were paresthesia (9.3%), weight loss (7.9%), convulsions (5.7%) and memory disorders (5.0%). Conclusion – In patients with epilepsy, previously not satisfactorily treated with CBZ or OXC, conversion to TPM may result in an improvement in seizure control as well as in quality of life. [ABSTRACT FROM AUTHOR]

Objectives – While carbamazepine (CBZ) decreases thyroid hormone concentrations it rarely causes hypothyroidism. We assessed prospectively the early effect of CBZ on thyroid status in thyroxine-supplemented hypothyroid patients, when compared with patients without a thyroid disorder. Methods – In 29 patients, thyrotropin (TSH), total thyroxine (TT4) and free thyroxine (FT4) serum levels were assayed before starting CBZ, and then weekly for 7 weeks. Nineteen patients with no thyroid disorder (group A) were compared with 10 thyroxine-supplemented hypothyroid patients, stable before CBZ treatment (group B). Results – In group A, TT4 decreased significantly by ca. 15–25%, starting from the first week (Friedman, P < 0.001). FT4 decline was smaller (ca. 10–15%) and delayed till the second week. FT4/TT4 ratio increased significantly ( P < 0.001), while TSH only slightly ( P = 0.073), never exceeding normal range. In group B, similar TT4 and FT4 decline was followed by significantly increasing TSH ( P = 0.011), while the FT4/TT4 ratio was not significantly changed. In 3 of 10 patients TSH rose over 5 mIU/l, necessitating treatment adjustment. Conclusions – In patients with no thyroid disorder, CBZ causes hormonal changes of no clinical relevance, due to adaptive response. In T4-supplemented hypothyroid patients this adaptation is lacking, CBZ may precipitate subclinical or overt hypothyroidism, and early thyroid function monitoring seems advisable. [ABSTRACT FROM AUTHOR]

Objectives – Interindividual variability in intestinal absorption and bioavailability might contribute to inadequate control of seizures under treatment with carbamazepine and phenytoin. We therefore correlated intestinal expression levels and genetics of CYP3A4, CYP2C9/19, MDR1 and MRP2 with dose requirement and plasma levels of carbamazepine and phenytoin. Materials and methods – Epileptic patients on carbamazepine ( n = 29) or phenytoin ( n = 15) were stratified into a ‘high’-dose (carbamazepine ≥800 mg/day, phenytoin ≥300 mg/day) and a ‘low’-dose group (carbamazepine ≤600 mg/day, phenytoin ≤200 mg/day). Duodenal biopsies and DNA were obtained for Western blotting and genotyping studies. Results – Low carbamazepine plasma levels showed a trend towards higher intestinal MDR1 expression ( P = 0.06). Furthermore, carbamazepine dose was positively correlated with MRP2 expression ( P = 0.1). Moreover, MDR1 expression and carbamazepine and phenytoin dose requirement was influenced by the genotype in position 2677 and 3435 of the MDR1 gene. Conclusion – Differences in intestinal MDR1 and MRP2 expression may influence carbamazepine and phenytoin disposition and may account for interindividual pharmacokinetic variability. [ABSTRACT FROM AUTHOR]

Objectives – To describe the choice of treatment in adult patients with epilepsy in Belgium, to detect the presence or absence of consensus among neurologists in epilepsy treatment, and to analyze the gaps between current guidelines and prescriptions. Materials and methods – Hundred Belgian neurologists were systematically interviewed between May and June 2003 using a structured questionnaire (modified Rand method). Results – Initial monotherapy was the preferred treatment strategy. Valproate was the first choice in idiopathic generalized epilepsy (IGE) and carbamazepine in focal epilepsy (FE). The new antiepileptic drugs (AED) were usually recommended in second-line. However, in special treatment situations, they were considered first-line, e.g., lamotrigine in case of women of childbearing age. Conclusions – Neurologists reached consensus for most questions on epilepsy treatment. In 2003, monotherapy with valproate and carbamazepine was the common treatment strategy in Belgium, whereas lamotrigine and to a lesser extent levetiracetam, topiramate, and oxcarbazepine were predominantly prescribed in second-line. This is in agreement with the recently published UK epilepsy guidelines but not in agreement, however, with the US guidelines, that for new onset epilepsy, new and old drugs are equally effective. Belgian neurologists, except for some special situations still prefer old drugs as first line. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of oxcarbazepine (1200 mg/day) in patients with painful diabetic neuropathy in a multicentre, double-blind, placebo-controlled, 16-week study. Methods: A total of 141 patients were randomized to oxcarbazepine (1200 mg/day) ( n = 71) or placebo ( n = 70). The primary efficacy variable was the change in mean visual analogue scale (VAS) score from baseline to the last week the patient participated in the study. Results: The reduction in mean VAS score from baseline to the last study week was similar between the oxcarbazepine and placebo groups. The majority of adverse events (most of which first occurred during titration) were mild to moderate in severity and resolved over the course of the study. Conclusions: In this study, no statistically significant difference in therapeutic effect was observed between oxcarbazepine (1200 mg/day) and placebo. However, further studies are necessary to assess the effective dose range of oxcarbazepine in the treatment of painful diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Criscuolo S, Auletta C, Lippi S, Brogi F, Brogi A. Oxcarbazepine monotherapy in postherpetic neuralgia unresponsive to carbamazepine and gabapentin.Acta Neurol Scand 2005 DOI: 10.1111/j.1600-0404.2005.00300.x© Blackwell Munksgaard 2005.We present the results of a preliminary, open-label trial to evaluate the efficacy and tolerability of oxcarbazepine in postherpetic neuralgia (PHN) unresponsive to treatment with antiepileptic drugs (carbamazepine and gabapentin) and local anesthetic blocks.Twenty-four patients were treated with oxcarbazepine monotherapy for 8 weeks. Starting dose was 150 mg/day, subsequently increased by 150 mg/day every 2 days until a maintenance dose of 900 mg/day. Pain was assessed using a visual analog scale (VAS).There was a significant decrease in the mean VAS score following 8 weeks of treatment (Δ = 5.33; pairedt-test:P < 0.0001) compared with baseline. Oxcarbazepine was effective from the first week of treatment. There was a significant reduction in allodynia, leading to improvements in patients’ functioning and quality of life. Oxcarbazepine was generally well tolerated.Oxcarbazepine appears to be a promising alternative monotherapeutic approach for patients affected by PHN. [ABSTRACT FROM AUTHOR]

P-Codrea (Tigaran) S, Sidenius P, Dam M. Lamotrigine-induced rash– worth a rechallenge.Acta Neurol Scand 2005: 111: 191–194.© Blackwell Munksgaard 2005.The only serious adverse event associated with lamotrigine (LTG) treatment is a hypersensitivity reaction primarily presenting as a rash. Despite this concern, LTG is an antiepileptic drug (AED) with one of the most favorable efficacy/tolerability ratio compared with the new as well as the old AEDs. Thus, this study aimed to evaluate the results of rechallenge with LTG after the initial rash.A total of 688 patients (350 as monotherapy, and 338 as add-on therapy) with either idiopathic generalized epilepsy or focal epilepsy were treated with LTG. The patients with LTG-induced rash were rechallenged to LTG. The dosage schedule was: 5 mg every day or every second day for 14 days, increased by 5 mg every 14th day to 25 mg a day. After achieving the daily dosage of 25 mg/day, the up-titration was completed following the current guidelines.A total of 52 patients developed a rash. The LTG-induced rash occurred in 6%, where 12 (1.8%) developed a rash shown to be coincidentally associated with the initiation of LTG therapy. In their cases LTG was continued with success without intermission. Nineteen (38%) of the initial cohort were rechallenged with LTG, with a success rate of 84%.This study is the first one to provide a successful recipe verified in time for the rechallenge with LTG after the initial drug-induced rash. Importantly, the concurrent use of valproate (VPA) was not found in this study to represent an additional risk factor for the occurrence of the rash during rechallenge with LTG. Our results agree with previous findings that women are more likely to develop the rash (P < 0.009). [ABSTRACT FROM AUTHOR]

Miller AD, Krauss GL, Hamzeh FM. Improved CNS tolerability following conversion from immediate- to extended-release carbamazepine. Acta Neurol Scand 2004: 109: 374–377. © Blackwell Munksgaard 2004. Tolerability of ‘narrow therapeutic ratio’ (NTR) antiepileptic drugs may improve with uniform drug delivery. We determined whether conversion from immediate-release carbamazepine (IR-CBZ) to extended-release carbamazepine (ER-CBZ) decreased the incidence of CNS side-effects associated with drug concentration oscillations. We compared CNS side effects and seizure frequency for patients with partial-onset seizures ( n = 61) treated with IR-CBZ for ≥1 year with conversion to ER-CBZ for ≥1 year. We compared tolerability findings with absorption variability of the formulations. Incidence of CNS side-effects decreased from 49% during IR-CBZ treatment to 20% following conversion to ER-CBZ. Patients also had improved tolerability of high doses (≥1200 mg/day) during ER-CBZ treatment. Pharmacokinetic analysis showed absorption and drug concentration were much more variable for the immediate-release formulation. This study suggests that ER-CBZ formulations, with smoother drug delivery and less variable absorption, provide improved CNS tolerability compared with immediate-release formulations. [ABSTRACT FROM AUTHOR]

Clemens B, Ménes A, Nagy Z. Objective assessment of neurotoxicity while shifting from carbamazepine to oxcarbazepine. Acta Neurol Scand 2003 DOI: 10.1046/j.1600-0404.2003.00234.x © Blackwell Munksgaard 2003. Objective assessment of non-overt neurotoxicity of carbamazepine (CBZ) vs oxcarbazepine (OXC) in patients with difficult-to-treat partial epilepsy, who were resistant to CBZ treatment and were converted from CBZ monotherapy to OXC monotherapy. Therapeutically equivalent doses (150 mg OXC for every 100 mg CBZ) were compared in 20 adult patients. Neurological investigation, conventional and spectral EEG analysis, brainstem auditory evoked responses (BAER) were carried out in both treatment conditions. EEG and BAER data of 20 age-matched healthy controls helped interpretation. Primary target variables (electrophysiological parameters) were evaluated blindly. There were no significant differences between treatment conditions concerning the neurological condition, lack of clinically evident neurotoxicity, seizure frequency and EEG spike frequency. OXC treatment was characterized by less delta, theta, and alpha power, more beta power, and significantly greater mean alpha frequency ( P = 0.03 and 0.05 for the left and right occipital leads, respectively), than CBZ treatment. Interpeak latencies were prolonged in the CBZ condition as compared with normals ( P = 0.01) and OXC ( P = 0.02). In this cohort of patients substitution of OXC for CBZ was associated with significant normalization of electrophysiological parameters, indicating decreasing neurotoxicity while shifting from CBZ to OXC monotherapy. [ABSTRACT FROM AUTHOR]

Tang Y, Glauser TA, Gilbert DL, Hershey AD, Privitera MD, Ficker DM, Szaflarski JP, Sharp FR. Valproic acid blood genomic expression patterns in children with epilepsy – a pilot study. Acta Neurol Scand 2003 DOI: 10.1046/j.1600-0404.2003.00253.x © Blackwell Munksgaard 2003. Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. The purpose of this pilot study is to examine the blood genomic expression pattern associated with VPA therapy in general and secondly VPA efficacy in children with epilepsy. Using oligonucleotide microarrays, gene expression in whole blood was assessed in pediatric epilepsy patients following treatment with VPA compared with children with epilepsy prior to initiation of anticonvulsant therapy (drug free patients). The expression of 461 genes was altered in VPA patients ( n = 11) compared with drug free patients ( n = 7), among which a significant number of serine threonine kinases were down-regulated. Expression patterns in children seizure free on VPA therapy ( n = 8) demonstrated 434 up-regulated genes, many in mitochondria, compared with VPA children with continuing seizures ( n = 3) and drug free seizure patients ( n = 7). VPA therapy is associated with two significant and unique blood gene expression patterns: chronic VPA monotherapy in general and a separate blood genomic profile correlated with seizure freedom. These expression patterns provide new insight into previously undetected mechanisms of VPA anticonvulsant activity. [ABSTRACT FROM AUTHOR]

Objectives – To compare topiramate (TPM) with investigator's choice of carbamazepine (CBZ) or valproate (VPA) for initial treatment in patients with newly diagnosed epilepsy. Material and methods – In patients with epilepsy diagnosed within previous 3 months, investigators selected CBZ (600 mg/day) or VPA (1250 mg/day) as preferred therapy based on the patient's clinical presentation. Based on investigators’ treatment choice, patients (n =613) were assigned to the CBZ or VPA treatment branch. Within each branch, patients were randomized to double-blind treatment with the traditional antiepileptic drugs (CBZ or VPA), TPM 100 mg/day, or TPM 200 mg/day. Patients continued double-blind treatment until exiting the study or until 6 months after last patient randomized. Results – No statistically significant differences between fixed doses of TPM and CBZ or VPA were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment. TPM 100 mg/day was associated with the fewest discontinuations due to adverse events. Conclusion – In patients with newly diagnosed epilepsy, an initial target dose of TPM 100 mg/day is at least as effective as therapeutic doses of CBZ and VPA. [ABSTRACT FROM AUTHOR]

Objectives – Some antiepileptic drugs (AEDs) are associated with low levels of serum (S-FA) and erythrocyte folate (E-FA) and high levels of plasma total homocysteine (p-tHcy). We have explored the concentrations of S-FA, E-FA and p-tHcy in patients on carbamazepine (CBZ). The methionine loading test was applied for better assessment of mildly impaired homocysteine metabolism. Material and methods – The study comprised 42 adult patients on CBZ and 42 matched healthy controls. Blood samples were drawn prior to and 6 h post methionine loading (6 h-PML) (0.1 g/kg body weight). Results – The patients on CBZ had significantly lower concentrations of fasting S-FA and E-FA than the controls (P=0.0004, P=0.003, respectively). Fasting and 6 h-PML p-tHcy concentrations were significantly higher in the patients than in the controls (P=0.03 and P=0.0001, respectively). The methionine loading test identified additional patients with hyperhomocysteinemia undetected by fasting p-tHcy. Conclusion – CBZ therapy may be associated with low folate and high p-tHcy levels. [ABSTRACT FROM AUTHOR]