Parent-reported subjective complaints in children using antiepileptic drugs: what do they mean?

We used a parent-completed 20-item "side effect scale" quantifying complaints that parents perceive to be caused by antiepileptic drugs (AEDs) in 108 children with active epilepsy. We studied the associations between parent-reported complaints, severity of seizures, and restrictions due to epilepsy, and clinical data including number and AED load. In 85% of the children at least one complaint was reported, in less than 20% complaints were perceived as a substantial problem. In a multivariate analysis, there was no significant relationship between the "side effect scale" score and AED load, or the number of AEDs. However, complaints were associated with parent-reported frequency and severity of seizures. We conclude that the adverse effects of seizures or parental concern about the severity and intractability of seizures in their children may have influenced the reported complaints.     

Epilepsy and antiepileptic drug therapy in juvenile neuronal ceroid lipofuscinosis

PURPOSE: To survey the characteristics of epilepsy in patients with juvenile neuronal ceroid lipofuscinosis (JNCL) and determine the antiepileptic drug (AED) treatment most suitable for these patients. METHODS: The study included 60 patients with JNCL; their mean age was 16.5 years (range 5-33). The age at onset of epilepsy, type of seizures, effect of the first AED on seizures, and the current seizure frequency and AED therapy were studied. The side effects of the AEDs were also clarified. RESULTS: Fifty of the 60 patients had epilepsy. Patients' first epileptic seizure occurred at a mean age of 10.0 years (range 5-16), the most common type being generalized seizures. As the first AED tried, valproate (VPA) and lamotrigine (LTG) appeared equally effective, with 80% of the patients responding to these AEDs. During the study year, the median seizure frequency was four seizures a year (range 0-120), and 72% of the patients had good or satisfactory seizure control (0-6 seizures a year). In the different AED therapy groups, the proportion of patients with good or satisfactory seizure control ranged from 25% to 100%. LTG in monotherapy or in combination with clonazepam (CZP) was superior to other AEDs or combinations, but VPA also seemed effective. Adverse effects leading to the discontinuation of an AED were observed in 25% of the patients, most frequently in patients receiving phenobarbital (PB). No patient receiving LTG had to discontinue the drug due to adverse effects. CONCLUSION: Epilepsy in JNCL can usually be successfully treated with the current AEDs. In Finnish patients with JNCL, treatment is based on LTG, or, secondarily, VPA. In combination therapy, CZP seems a valuable add-on AED.     

Postmarketing experience with topiramate and cognition

Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double-blind, placebo-controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open-label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment. We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with "better" or "much better" ratings of both seizure and global improvement during treatment.     

Seizures and therapy in adolescents with uncomplicated epilepsy.

PURPOSE: This study aimed to describe seizures and their therapy among Swedish adolescents, aged 13-22, with active but uncomplicated epilepsy. METHOD: The adolescents answered questionnaires (158/193). Data were also obtained from medical records. RESULTS: Epileptic seizure types could be specified in 92.1% of the cases. Predominant types were Primary Generalised Tonic-Clonic Seizures and Partial Complex Seizures with Secondary Generalisation. Clinical diagnoses by physicians were unspecified in 25.8%. Ninety percent were on antiepileptic drugs (AEDs), most commonly valproate and carbamazepine. New AEDs were used in 9.3% of the cases and polytherapy in 13.9%. More than 40% of the respondents had seizures despite AED treatment. Side effects of AEDs were experienced by 61%, most commonly tiredness, concentration difficulties and headache. Patients on polytherapy experienced significantly more side effects. The choice of a new AED over a traditional one was not related to seizure type or seizure control. CONCLUSIONS: Many adolescents had persistent seizures despite treatment at a specialist regional epilepsy centre. This, plus the high reported rate of side effects of AED treatment, suggests that treatment is not optimal for the group studied. As traditional AEDs strongly dominated treatment possibly newly marketed AEDs are underused in this group.     

The specialist nurse role in the treatment of refractory epilepsy.

The main aim of epilepsy treatment is rapid and complete control of seizures without antiepileptic drug (AED) side effects. This outcome is achieved in 60-70% of newly diagnosed patients. In refractory epilepsy, new AEDs render some additional patients seizure free but make treatment more complex. The choice of AEDs, their differing pharmacokinetics, efficacy, tolerability and potential interactions are multiplied. Up to of 75% of patients develop AED side effects, most AEDs can cause paradoxical reactions, and when AED doses are changed seizures may worsen. Despite the increased complexity of epilepsy treatment and the biomedical and psychosocial consequences of uncontrolled seizures, many patients have difficulty accessing specialist services. A service that involves the epilepsy nurse specialist (ENS) giving patients and General Practitioners (GPs) free access to treatment advice has recently been established to improve care. Over a 2-week period 60 treatment-related telephone or outpatient consultations were provided out of a total of 124 contacts. Changes to the AED regimen were implemented in 44/60, and the GP was notified by letter in 31/44. The audit results are presented and epilepsy treatment including AED efficacy, tolerability, interactions and side effects are discussed.     

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 20000 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.     

Adjustment of treatment increases quality of life in patients with epilepsy: a randomized controlled pragmatic trial

Background and purpose:  Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial.
Methods:  This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events.
Results:  After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04–3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88–2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed.
Discussion:  In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life.     

Relationship between adverse effects of antiepileptic drugs,number of coprescribed drugs,and drug load in a large cohort of consecutive patients with drug‐refractory epilepsy

Purpose: To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load. Methods: Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED. Results: Of 809 patients enrolled, 709 had localization‐related epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 ± 0.5 for patients on monotherapy to 2.5 ± 1, 3.7 ± 1.1, and 4.7 ± 1.1 for those on two, three, and ≥4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p < 0.0001). AEP scores did not differ between patients with monotherapy and patients with polytherapy (42.8 ± 11.7 vs. 42.6 ± 11.2), and there was no correlation between AEP scores and AED load (r = ?0.05, p = 0.16). Conclusions: AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load, possibly as a result of physicians’ intervention in individualizing treatment regimens. Taking into account the limitations of a cross‐sectional survey, these findings are consistent with the hypothesis that AEs are determined more by individual susceptibility, type of AEDs used, and physicians’ skills, than number of coprescribed AEDs and AED load.     

Challenging epilepsy with antiepileptic pharmacotherapy in a tertiary teaching hospital in Sri Lanka

The goal of antiepileptic drug (AED) therapy is to achieve a seizure-free state and eliminate the medical and psychosocial risks of recurrent seizures. Burden of epilepsy on the economy of a country may be largely due to the expenditure on AEDs. The adverse effects may influence the compliance to AEDs and effective control of epilepsy. We determined the pattern of AED use, the degree of epileptic control achieved and the adverse effects experienced by the epileptics in a Tertiary Teaching Hospital in Sri Lanka. Carbamazepine was found to be the most frequently used AED. Monotherapy was used on 70.8% of subjects. 86.27% of the study sample had achieved effective control of epilepsy with a 50% or more reduction in seizure frequency. Of them 72.64% were on monotherapy and they were either on carbamazepine, sodium valproate, phenytoin sodium or phenobarbitone. None of the new AEDs were prescribed to these patients. 50.9% on monotherapy and 51.5% on polytherapy reported adverse effects. Somnolence followed by headache was found to be the most frequently reported adverse effects by those on monotherapy and polytherapy both. This study shows that most epileptics can be effectively managed with the conventional AEDs with clinical monitoring.     

Drug selection for the newly diagnosed patient: When is a new generation antiepileptic drug indicated?

Abstract. Treatment options in epilepsy have increased dramatically since the early 1990s with the introduction of nine new generation antiepileptic drugs (AEDs) (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide). This makes drug selection much more complicated and challenging. This review discusses drug selection in patients with newly diagnosed epilepsy and in particular the role of new AEDs in this population. The choice of treatment should always be based on a careful comparison of the risk-benefit ratio for the different treatment options and the outcome of such evaluation may be different in patients with new onset compared with chronic epilepsy. Efficacy, tolerability and safety are the main criteria for selection of AEDs and any first line drug for patients with newly diagnosed epilepsy must have demonstrated satisfactory efficacy as monotherapy in that patient population. So far, of the new AEDs only lamotrigine, oxcarbazepine and topiramate have documentation sufficient to be granted licence for use as monotherapy in most European countries. Because the new generation AEDs have failed to demonstrate improved effectiveness as monotherapy, old generation AEDs such as carbamazepine and valproate remain drugs of first choice for partial and generalised seizures, respectively. However, there are special situations and populations where a new AED may be a reasonable first line drug. These include vigabatrin in West syndrome associated with tuberous sclerosis, lamotrigine as alternative to valproate in idiopathic generalised seizures in women of childbearing potential and lamotrigine for the treatment of epilepsy in the elderly population. The role of the new generation AEDs is likely to become more prominent as more experience is gained.     

Strategies to prevent overtreatment with antiepileptic drugs in patients with epilepsy

Overtreatment is defined here as an unnecessary and excessive drug load in the management of epilepsy leading to a suboptimal risk-to-benefit balance. Pharmacological overtreatment can often be prevented by deciding and counselling carefully about the need for antiepileptic drugs (AEDs) given the limitations of current AEDs. Although AEDs will reduce the incidence of seizures, they have no demonstrated ability to prevent epilepsy in patients at risk or to modify the course of epilepsy in patients following the first seizure. In addition, starting AEDs may not be necessary for control of epileptic seizures induced by precipitation or predisposing factors or for benign epilepsies with rare or mild seizures. Start monotherapy with the chosen first-line AED, initially at low doses titrating up to the low maintenance dose. Avoid drug loading (except for emergency treatment). If seizures continue, titrate to the limit of tolerability which will however, achieve additional seizure control in approximately 20% of patients. If, as in many patients, dosing to the limit of tolerability is not beneficial, the dose should be reduced. Switching to an average dose of another first line AED is another option to prevent overtreatment. Avoid drug overload during add-on therapy by slowly reducing the dose of the first drug in patients having adverse effects, ideally by an amount that the patient does not experience any further adverse effects, if possible, before adding another drug. If the patient does not benefit unequivocally from two-drug therapy within 3 months (and approximately 75% will not benefit), slowly transfer to monotherapy of the second drug and start with a newly chosen AED for add-on. To counteract the propensity to overmedication in chronic epilepsy is not easy. Great benefits, without loss of seizure control, are often gained by slowly reducing the overall drug load.     

Long-Term Experience with Topiramate as Adjunctive Therapy and as Monotherapy in Patients with Partial Onset Seizures: Retrospective Survey of Open-Label Treatment

Summary: Because initial studies of new antiepileptic drugs (AEDs) are add-on trials in refractory patient populations, their effectiveness as monotherapy is usually not apparent until relatively later in their development programs. The novel AED topiramate (TPM) has been found efficacious as adjunctive therapy in controlled, randomized trials in adults with partial onset seizures. We report a retrospective analysis of TPM as AED monotherapy in 214 patients from five centers who received TPM in investigational trials. Of this total, 136 (64%) were still receiving TPM at the time of the analysis, with a mean treatment duration of 2.5 years. One-third of the patients have been successfully converted to TPM monotherapy, and 62% of those converted have been seizure-free for at least 3 months. The results of this analysis suggest that TPM may prove to be a valuable new AED for both monotherapy and add-on therapy in partial onset epilepsy.     

Practical strategies for switching to newer antiepileptic drugs

Traditional antiepileptic drugs (AEDs) are associated with drug interactions and side effects that limit their safety and tolerability. Side effects of traditional AEDs are especially problematic for children and adolescents, women of childbearing age, and the elderly. Many patients with epilepsy may benefit from switching from a traditional AED to a newer agent because the newer agents are generally better tolerated and are less likely to cause drug interactions. Clinical studies have demonstrated improved therapeutic efficiency with better tolerability in patients switching from a traditional AED to lamotrigine, oxcarbazepine, or topiramate monotherapy or combination therapy.     

Transient improvement after brief antiepileptic drug withdrawal in the epilepsy monitoring unit—possible relationship to AED tolerance

Purpose: A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance. Methods: We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission. Results: A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 ± 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 ± 23.8 days) than patients on polytherapy (13.9 ± 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 ± 36.8 days) compared to patient with no prior history of AED tolerance (14.0 ± 16.3 days). Discussion: SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.     

Antiepileptic drug therapy for adult patients with intractable seizures]

Epileptic syndrome, antiepileptic drug (AED) therapy and mental disorder were studied in 223 patients with intractable epilepsy, who were admitted to our epilepsy center between 1992 and 2000. Symptomatic localization-related epilepsy was diagnosed in 86.1% of patients, symptomatic or cryptogenic generalized epilepsy in 7.6%, idiopathic generalized epilepsy in 1.8%, unclassifiable epilepsy in 3.1% and non-epilepsy in 1.3% on discharge. Only 6.3% had diagnoses on discharge that were incongruent with their diagnoses on admission. AED therapy during admission improved markedly in 50% of patients and moderately in 20%, however, 60% had seizures more frequently than 4 a month on discharge. Generalized tonic and clonic seizures were suppressed completely in 82.5% of patients. The number of AEDs used were 2 AEDs in 28.6%, 3 in 39.1% and 4 in 22.3%. Only 6.4% of patients were on monotherapy on discharge. Mental retardation was in 58.7%, schizophrenia-like psychosis in 8.5%, delusional disorder in 1.8%, mood disorder in 3.6%, AED-related disorder in 14.3% and psychogenic disorders in 21.5%. AED therapy is effective for intractable seizures, but it is limited in its effect. Mental disorders also coexisted in most of patients. Therefore comprehensive therapy of epilepsy is necessary for patients with intractable seizures.     

Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study)

OBJECTIVE: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health-related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied. METHODS: Patients, seizure-free for more than 2 years on AED monotherapy, were recruited for a controlled, prospective, randomized, double-blinded withdrawal study lasting for 12 months, or until seizure relapse. Patients were randomized to AED withdrawal (n = 79) and nonwithdrawal (n = 81) groups. The examination program included clinical neurological examinations, neuropsychological testing, EEG-recordings, cerebral MRI, and assessments of HRQOL. Follow-up data on seizure relapse were also collected beyond the 12-month study period (median 47 months). RESULTS: Seizure relapse at 12 months occurred in 15% of the withdrawal group and 7% of the nonwithdrawal group (RR 2.46; 95% CI: 0.85-7.08; p = 0.095). After withdrawal, seizure relapse rates were 27% after a median of 41 months off medication. A normal result to all 15 neuropsychological tests increased significantly from 11% to 28% postwithdrawal. We found no significant effects of withdrawal on quality of life and EEG. Predictors for remaining seizure-free after AED-withdrawal over 1 year were normal neurological examination and use of carbamazepine prior to withdrawal. CONCLUSION: Seizure-free epilepsy patients on AED monotherapy who taper their medication may improve neuropsychological performance with a relative risk of seizure relapse of 2.46, compared to those continuing therapy.     

Quality of life in seizure-free patients with epilepsy on monotherapy

Epilepsy is a multifaceted chronic disorder which has diverse and complex effects on the well-being of the patient. Although it is evident that seizure type and frequency play a critical role in the quality of life (QOL) of patients with epilepsy, it is less clear what the major determinants are that influence QOL in seizure-free patients receiving monotherapy. The aim of this study was to evaluate demographic, clinical, and socioeconomic factors influencing the QOL of seizure-free patients receiving monotherapy. All participants were patients from four medical centers who had epilepsy, were on monotherapy, and had been seizure-free for at least 1 year. Responders completed three questionnaires on demographic and clinical information, QOL, and antiepileptic drug (AED) side effects during routine follow-up visits in the epilepsy clinics. We present the data of 103 patients: 59 females (57.3%), mean age 37.75+/-13.66 years. Treatment side effects and unemployment (p<0.0001, p=0.037, respectively) were significant predictors for poor overall QOL, whereas age, gender, education, family status, comorbidity, seizure type, age of seizure onset, and epilepsy duration did not significantly affect overall QOL. There was no significant difference in side effects and QOL between patients receiving older versus newer AEDs. Ninety-four (92.2%) patients reported experiencing at least one side effect of AEDs when queried about specific symptoms, while only 11 (10.7%) patients replied affirmatively when asked whether they experienced "any" side effects. The most common side effects involved the central nervous system. In conclusion, this study reveals that the most significant factor influencing the QOL in seizure-free patients on monotherapy is AED side effects. QOL is a crucial component in the clinical care of patients with epilepsy, and physicians should take the time to ask specific questions on side effects of AEDs.     

Clinical characteristics and use of antiepileptic drugs among adolescents with uncomplicated epilepsy at a referral center in Novi Sad, Serbia

The study aimed to investigate the type and etiology of epileptic seizures and the use of antiepileptic drugs for the treatment of various forms of epileptic seizures among adolescents with active but uncomplicated epilepsy at a tertiary referral center in Novi Sad, Serbia. The study design was cross sectional. Data were obtained from patients and medical records. A total of 103 adolescents (39 males and 64 females) with active but uncomplicated epilepsy were included. Patients with primary generalized seizures had significantly better control of epilepsy than those with partial seizures with or without secondary generalization. A total of 80 (77.7%) adolescents had no known underlying etiology based on initial diagnosis and evaluation. All adolescents were classified into known idiopathic syndromes (54.4%), non-classifiable cryptogenic etiology (23.3%), and secondary epilepsy attributed to MRI-identified lesions (22.3%). Eighty-eight percent of adolescents were taking monotherapy and 64.8% of these were taking valproate. New antiepileptic drugs (AEDs), topiramate and lamotrigine, the only drugs available free of charge at the Serbian market, were used in 19.4% of patients. A total of 57.3% adolescents were seizure-free, 24.2% had occasional seizures, and 18.5% had seizures despite AED treatment.     

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.