Chronic Antiepileptic Drug Research Articles

Alteration in Bone Metabolism and Bone Mineral Density with Chronic Antiepileptic Drug Therapy

Alteration in Bone Metabolism and Bone Mineral Density with Chronic Antiepileptic Drug Therapy

Abstract 76: Alteration in bone metabolism and bone mineral density with chronic anti-epileptic drug therapy in North Indian population

Objective: Anti-epileptic drugs are the mainstay of treatment of epilepsy. Prolong use of anti-epileptic medicines can lead to reduction in bone mineral density (BMD), resulting in 2-6-fold increase in fracture risk. This study was carried out to assess the impact of AEDs on the markers of bone turnover and BMD in North Indian patients.Methods: In this hospital based observational study sixty adult patients with epilepsy, on antiepileptic drugs were included. Serum calcium, phosphorus, alkaline phosphatase (ALP), albumin, 25 (OH) vitamin D and intact Parathyroid hormone (iPTH) and BMD (at lumbar spine with DEXA) were measured in all study subjects.Results: The serum level of calcium, phosphorus and 25(OH) Vitamin D was significantly decreased and iPTH and ALP levels were increased in patients taking anti-epileptic drugs for > 5 years. There was a significant negative correlation between serum calcium, phosphorus and vitamin D levels and significant positive correlation with ALP and iPTH levels with duration anti-epileptic therapy. There was negative correlation between the T-score and anti-duration of anti-epileptic therapy.Conclusions: Use of anti-epileptic (both old and new) medication in adults is associated with decline in BMD, calcium, vitamin D and phosphorus levels and elevation in iPTH and ALP levels.

Farmaci antiepilettici, vitamina D e mineralizzazione ossea: le evidenze e le azioni

The possible negative effects of antiepileptic drugs on bone metabolism with the consequent possible risks have been discussed in the literature for more than 30 years. Two reviews of the literature attempted to answer the following clinical questions: “Should vitamin D supplementation be used in children receiving antiepileptic drugs?”, “Do children on chronic antiepileptic drug therapy have to perform bone densitometry (DEXA) to assess the state of bone mineralization”? The evidence suggests to prescribe a prophylaxis with vitamin D at 400 IU/day to children on antiepileptic therapy and without other risk factors and provide them with indications regarding correct eating, motor and sun exposure lifestyles. Higher doses will be evaluated in case of coexistence of risk factors. DEXA screening may be useful in children on antiepileptic therapy and with a history of fractures (particularly multiple or low impact fractures) or in children on prolonged antiepileptic therapy and in the presence of additional risk factors (e.g. infantile cerebral palsy).

High prevalence of vertebral fractures in seizure patients with normal bone density receiving chronic anti-epileptic drugs.

Chronic use of antiepileptic drugs (AEDs), both enzyme-inducing (phenytoin, phenobarbital, carbamazepine, and primidone) and non-enzyme-inducing (i.e., valproate), is recognized as acauseof secondary osteoporosis. Vertebral compression fractures (VF) are the most common type of osteoporotic fractures and may confer an increased risk of future hip, wrist, and vertebral fractures. Vertebral compression fractures in the general population are frequently asymptomatic, and under-diagnosed. The purpose of this study is to describe the prevalence of VF in a cohort of male veterans with epilepsy on chronic AEDs. The cohort for this study consisted of 146 male veterans who carried a diagnosis of epilepsy and were chronic users of AEDs known to cause osteoporosis (phenobarbital, phenytoin, carbamazepine, primidone, and valproate). Chronic AED use wasdefined as receiving an AED for at least 2 years. Subjects were previously seen in the osteoporosis clinic and had been evaluated by a dual-energy X-Ray absormetry (DXA) instrument including morphometric studies following a standard vertebral fracture assessment (VFA) protocol during the same DXA imaging acquisition session. The mean age was 63 years. Low bone mineral density defined as osteoporosis or osteopenia was observed in 29% and 43% respectively. We observed at least one VF in 41 % of the subjects who had normal BMD, 54% in the osteopenic range, and 75% in the osteoporotic range. By performing a VFA in addition to standard bone densitometric studies, we disclosed a large prevalence of compression fractures in individuals with epilepsy chronically treated with AEDs who had BMDs in the normal and osteopenic ranges. The addition of VFA or other imaging methods to evaluate VF should be included in the evaluation of bone health in individuals with epilepsy receiving AEDs since it may modify treatment recommendations to prevent future osteoporotic fractures.

Clinical guide: discontinuing chronic antiepileptic drug treatment

Clinical guide: discontinuing chronic antiepileptic drug treatment

First‐ever convulsive seizures in children presenting to the emergency department: risk factors for seizure recurrence and diagnosis of epilepsy

Aetiologies of first-ever convulsive seizures may be diverse, not all leading to recurrence or epilepsy diagnosis. We aimed to describe the epidemiology of first-ever convulsive seizures in children, investigating risk factors for recurrence and epilepsy diagnosis. This was a retrospective study of children presenting with a first-ever convulsive seizure to a tertiary-care paediatric emergency department (PED) in Italy, in a 12-month period (2011-2012). One hundred and eight children (57 males, 51 females) presented to the PED for a first-ever convulsive seizure; 90.7% were 6months to 6years old (median age 1y 10mo, mean 2y 7mo, range 0mo-14y 4mo). Seizure duration was less than 5minutes in 76.8%. Seizures were 'unprovoked' in 19.4% and 'provoked' in 80.6%. At 4-year follow-up, 37.9% of patients experienced recurrence and 13.6% received a diagnosis of epilepsy. Factors significantly associated with recurrence were the 'unprovoked' nature of the first seizure, multiple seizures in the first 24hours, positive family history of febrile seizures or epilepsy, and pre-existing neurological conditions/problems. Factors significantly associated with a diagnosis of epilepsy were the 'unprovoked' nature of the first seizure, age older than 6years, pre-existing neurological conditions/problems, and focal onset of first seizure. Children presenting to the PED with first-ever convulsive seizures represent a heterogeneous group. The identification of prognostic factors for recurrence and epilepsy diagnosis may help provide tailored counselling and follow-up. Seizures were 'unprovoked' in 19.4% and 'provoked' in 80.6% of children presenting to the emergency department. At 4-year follow-up, 37.9% relapsed, and 13.6% received a diagnosis of epilepsy. 'Unprovoked' first seizure, family history of febrile seizures, and pre-existing neurological conditions were associated with recurrence. 'Unprovoked' first seizure, age younger than 6years, and pre-existing neurological conditions were associated with epilepsy diagnosis.

Early Recurrence of First Unprovoked Seizures in Children

The risk of early seizure recurrences after first unprovoked seizures in children is largely unknown. We aimed to determine the rate of seizure recurrence within 14 days of first unprovoked seizures in children and identify associated risk factors. Secondarily, we aimed to determine the risk of recurrence at 48 hours and 4 months. We conducted a secondary analysis of a multicenter cohort study of children 29 days to 18 years with first unprovoked seizures. Emergency department (ED) clinicians completed standardized histories and physical examinations. The primary outcome, recurrent seizure at 14days, and the secondary outcomes, recurrence at 48 hours and 4 months, were assessed by telephone follow-up and medical record review. For each recurrence time point, we excluded those patients for whom no seizure had recurred but chronic antiepileptic drugs had been initiated. A total of 475 patients were enrolled in the parent study. Of evaluable patients for this secondary analysis, 26 of 392 (6.6%, 95% confidence interval [CI]= 4.4%-9.6%) had recurrences within 48 hours of the incident seizures, 58 of 366 (15.8%, 95% CI= 12.3%-20.0%) had recurrences within 14 days, and 107 of 340 (31.5%, 95% CI= 26.6%-36.7%) had recurrences within 4 months. On logistic regression analysis, age younger than 3 years was independently associated with a higher risk of 14-day recurrence (adjusted odds ratio [OR]= 2.1, 95% CI= 1.2-3.7; p=0.01). Having had more than one seizure within the 24 hours prior to ED presentation was independently associated with a higher risk of seizure recurrence at 48hours (adjusted OR= 4.3, 95% CI= 1.9-9.8; p<0.001). Risk of seizure recurrence 14 days after first unprovoked seizures in children is substantial, with younger children at higher risk. Prompt completion of an electroencephalogram and evaluation by a neurologist is appropriate for these children.

Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study

AIMTo increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment.METHODSThe relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A “low risk” category (lamotrigine or levetiracetam, n = 16), an “intermediate risk” category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a “high risk” category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment.RESULTSCentral information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant (P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category (P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed.CONCLUSIONOnly the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

Drug-Drug Interactions Among Hospitalized Children Receiving Chronic Antiepileptic Drug Therapy.

Children treated with chronic medications are at risk of drug-drug interactions (DDIs) when hospitalized with an acute illness and prescribed new medications. We aimed to measure the prevalence of potential DDIs (pDDIs) among hospitalized children treated with antiepileptic drugs (AEDs) and to evaluate the impact of computerized physician order entry (CPOE) on pDDIs. We analyzed a national sample of pediatric hospitalizations from 2005 to 2012 associated with administration of an AED and identified those prescribed a second medication with risk of a DDI. The prevalence of hospitalizations associated with a pDDI was calculated for each AED. We identified the drugs most commonly implicated in pDDIs and factors associated with pDDIs. Rates of pDDIs were measured in pre- and post-CPOE implementation periods. A pDDI was identified in 181 380 (41.7%) hospitalizations associated with the use of an AED, with 117 880 (27.1%) classified as severe pDDIs. AEDs most often implicated with a pDDI were phenobarbital, valproic acid, and phenytoin. Hospitalizations with pDDIs were associated with increased length of stay and a greater number of medications, ICU admissions, and operating room procedures. The implementation of CPOE did not result in a change in the rate of pDDIs (42.7% before versus 40.8% after; P = .48). Children treated with AEDs are at risk of pDDIs while hospitalized. The use of CPOE has not been associated with a significant decrease in the rate of pDDIs. Additional investigation to better define the impact of pDDIs and to advance development of clinical decision support within CPOE systems is warranted.

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs.

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine.

IMPACT OF ANTIEPILEPTIC DRUGS ON COGNITIVE FUNCTIONS: FOCUS ON PERAMPANEL

Cognitive problems in epilepsy have a multifactorial origin with etiology, seizures, and the «central» side-effects of drug treatment being involved. Cognitive side effects of antiepileptic drugs (AEDs) have been demonstrated to be one of the most important tolerability problems in chronic AED treatment, especially in children with epilepsy. Memory impairments, mental slowing, and attentional deficits are the most frequently reported ones. Neuropsychological profiles of AEDs are important considerations for treatment selection, particularly in children and adolescents. In evaluating studies of the cognitive effects of AEDs we must follow an evidence-based approach, but in the majority of cases, specific data on cognitive functions in children and adolescents with epilepsy are not yet available. A randomized double blind trial on cognitive effects of adjunctive perampanel for partial-onset seizures is cited (Meador K. F. et al, 2015) and discussed. In this trial adjunctive perampanel did not have any significant overall negative cognitive effect and was improving episodic memory in adolescent patients with inadequately controlled partial-onset seizures.

Antiepileptic drug use and epileptic seizures in nursing home residents in the Province of Pavia, Italy: A reappraisal 12 years after a first survey

PurposeTo assess the prevalence of epileptic seizures, and antiepileptic drug (AED) use among nursing home elderly residents; to evaluate demographics, seizure characteristics, and seizure-related comorbidities associated with institutionalization; and to compare findings with a previous survey conducted 12 years earlier. MethodsData on demographics, age at institutionalization, diagnoses, functional and cognitive status (Barthel Index and Mini Mental State Examination) and drug treatment were obtained by review of medical records of all individuals aged ≥60 years at 21 nursing homes. Data from individuals with a diagnosis of epileptic seizures and AED users were compared with non-seizure, non-AED individuals. ResultsAmong the 2163 individuals surveyed (79% females, age at observation 84.9±7.8 years, mean±SD), 278 (12.8%, vs 4.3% in the previous survey) received chronic AED treatment, including 174 who did not have a diagnosis of seizures. Of the 116 residents with a diagnosis of seizures (5.4%, vs 2.9% in the previous study), 104 were on AED treatment and were younger and had lower cognitive abilities, and a higher number of comorbidities and co-medications compared with non-AED-users. The most commonly prescribed AEDs in seizure individuals were phenobarbital (43.3%, vs 70% in the previous survey) and levetiracetam (27.9%, not available at the time of previous survey). At multivariate analysis, a diagnosis of seizures was found to be associated with younger age at the time of the survey, a history of neurological (cerebrovascular events, meningiomas) and non-neurological conditions (psoriasis and chronic bronchitis), and a lower MMSE score. ConclusionsThe prevalence of seizures and AED use was higher than in our previous survey and more aligned with data from other countries. Seizures, AED use and co-morbidities were associated with earlier institutionalization. There were indicators of treatment being suboptimal in many cases.

Changes in balance function with chronic antiepileptic drug therapy: A twin and sibling study.

To investigate cross-sectional and longitudinal differences in static and dynamic standing balance measures and lower limb muscle strength in patients who are treated chronically with antiepileptic drugs (AEDs). Twenty-six AED exposure-discordant same-gender twin and sibling pairs were studied. Clinical and laboratory balance examinations were conducted twice, separated by at least 1 year. The mean within-pair differences in balance measures were calculated cross-sectionally at baseline and follow-up, and longitudinally. No significant mean within-pair difference was found at baseline in age (44 years), weight, and height (p > 0.05). Between study assessments, the median (interquartile range [IQR]) interval was 3.0 (2.1-4.3) years in users and 2.9 (2.0-4.4) years in nonusers. The median duration of AED therapy was 19 (11-21) years. At baseline and follow-up, cross-sectional sway measures from posturography (Chattecx Balance System) and clinical static balance tests showed poorer performance in users compared to nonusers on several test conditions (p = 0.002-0.032). At follow-up, the users took longer than nonusers to complete the Four-Square-Step Test (p = 0.005) and Five-Times-Sit-to-Stand Test (p = 0.018). A greater annual rate of deterioration in sway was found in users compared to nonusers using posturography on the anteroposterior tilting platform task with distraction (p = 0.032). In both groups, higher baseline sway predicted greater annual deterioration in sway in all platform conditions (β = 0.3-0.5, p < 0.001-0.013). The annual change in measures did not differ between groups in the clinical balance and lower limb strength assessments. In this longitudinal twin and sibling study, chronic AED users had poorer standing balance compared to nonusers. Users showed greater deterioration in postural sway with one dynamic platform condition. AEDs may progressively impair balance mechanisms, although this requires further investigations. Repeated dynamic posturography could provide a basis for preventive trials for maintaining or improving balance.

Medical Treatment in Childhood Epilepsies

Summary The majority of epileptic seizures are controlled with antiepileptic drugs (AEDs). Whether or not to start treatment following an initial unprovoked seizure should be decided on an individualized basis; and, the risk of seizure recurrence versus possible side-effects and social conse quences of chronic AED treatment should be evaluated. Main risk factors for seizure recurrence can be summarized as the presence of focal seizure types, organic brain lesion, focal neurologic abnormality, previous neurodevelopmental retardation, specific EEG abnormality and positive family history of epilepsy. The AED chosen for initial therapy should be one that is highly effective for a particular seizure type and epilepsy syndrome, as also, that is safe and well tolerated. Monotherapy is the goal in epilepsy treatment. If the first two monotherapies fail, combinations of AEDs should be tried. Withdrawal of AED therapy should be considered in most children after two years without seizures. AEDs should be tapered slowly rather than halted abruptly.

Withdrawal of antiepileptic drugs: Guidelines of the Italian League Against Epilepsy

The Italian League Against Epilepsy has issued evidence-based guidelines to help practicing physicians in their decision to stop or withhold antiepileptic drugs (AEDs) in patients achieving a prolonged period of seizure freedom. Six adult and two child neurologists, divided into four pairs, critically appraised 128 published reports and provided graded recommendations answering 15 key questions: length of the seizure-free period after treatment initiation, difference in seizure-free periods in children and adults, electroencephalography (EEG) pattern at the time of discontinuation, etiology of epilepsy, seizure type(s), patient's age and sex, family history of epilepsy, history of febrile seizures, epilepsy syndrome, seizure frequency before entering remission, duration of active epilepsy, tapering period, number and type of AEDs taken at time of discontinuation, combination of risk factors for recurrence, and length of patient monitoring after treatment discontinuation. Based on the available data, the following recommendations can be outlined: (1) antiepileptic treatment might be discontinued after a minimum period of 2 years of seizure freedom; shorter seizure-free periods are associated to a higher risk of relapse; (2) in children, AED discontinuation could be considered after less than two seizure-free years because of a marginally higher risk of relapse for early withdrawal; (3) factors, such as abnormal EEG (including epileptiform abnormalities) at the time of treatment discontinuation, a documented etiology of seizures (including mental retardation, perinatal insults, and abnormal neurologic examination), partial seizures, or an older age at disease onset, enhance the risk of relapse; however, patients should not be encouraged to withhold treatment unless a combination of two or more of these factors is present; (4) female sex, family history of epilepsy, history of febrile seizures, disease length/severity, and number and type of drugs taken should not influence the decision to stop treatment; (5) epilepsy syndrome should be always included in the decision process; (6) slow (at least 6 months) AED discontinuation should be encouraged; in any case the duration of the tapering period should be tailored to the patient's needs and preference; and (7) patient discontinuing treatment should be followed for no <2 years. As a general habit, the decision to stop treatment should be discussed and shared with each patient, taking into account social and personal complications of a seizure relapse and the medical complications of chronic AED treatment.

Safe Treatment of Seizures in the Setting of HIV/AIDS

HIV(+) patients are at increased risk for developing seizures due to the vulnerability of the central nervous system to HIV-associated diseases, immune dysfunction, and metabolic disturbances. In patients with acute seizures, standard protocols still apply with urgent seizure cessation being the priority. Management of the person with established epilepsy who contracts HIV is challenging, but the decision to initiate chronic antiepileptic drug (AED) therapy in an HIV(+) patient is also difficult. Chronic treatment guidelines emphasize the interactions between AEDs and antiretroviral (ARV) medications, but provide no explicit advice regarding when to initiate an AED, what medication to select, and/or the duration of treatment. Epidemiologic data regarding seizure recurrence risk in HIV(+) individuals is not available. The risk of further seizures likely depends upon the underlying etiology for the seizure(s) and patients' immune status and may be increased by the use of efavirenz (an ARV). The issues for consideration include AED-ARV interactions, organ dysfunction, seizure type, and drug side effects, which may worsen or be confused with symptoms of HIV and/or epilepsy. Co-administration of enzyme inducing (EI)-AEDs and ARVs can result in virological failure, breakthrough seizure activity, AED toxicity, and/or ARV toxicity. Where available, the AED of choice in HIV(+) patients is levetiracetam due to its broad spectrum activity, ease of use, minimal drug interactions, and favorable side effect profile. Lacosamide, gabapentin, and pregabalin are also favored choices in patients with partial onset seizures and/or those failing levetiracetam. Where newer AEDs are not available, valproic acid may be the treatment of choice in terms of an AED, which will not cause enzyme induction-associated ARV failure, but its side effect profile causes other obvious problems. In resource-limited settings (RLS) where only EI-AEDs are available, there are no good treatment options and further pressure needs to be placed upon policymakers to address this care gap and public health threat.

Dual-energy X-ray absorptiometry versus quantitative ultrasonography in diagnosing osteoporosis in patients with refractory epilepsy and chronic antiepileptic drug use

The aim of this study was to assess the feasibility of calcaneal quantitative ultrasonography (QUS) as a screening method for increased risk of osteoporosis in a unique population of people with chronic epilepsy, intellectual disability (ID), and chronic use of antiepileptic drugs. A total of 205 patients from a long-stay care facility for people with epilepsy underwent dual-energy X-ray absorptiometry (DXA) and QUS of the calcaneus. T-scores for both DXA and QUS were calculated and correlated. A total of 195 patients (95.1%) were successfully measured with DXA and 204 (99.5%) with QUS. High correlations were found between DXA and QUS T-scores: r = 0.666 (QUS versus T-score total femur), r = 0.631 (QUS versus T-score femur neck) and r = 0.485 (QUS versus T-score lumbar spine). All correlations were statistically significant (p = 0.01). QUS showed a strong correlation with DXA and proved to be a feasible measuring method in a population with ID and epilepsy. Including osteopenia in the screening process increases the sensitivity of QUS to identify those patients at risk for the development of bone diseases.

The cost of implementing a nationwide program to decrease the epilepsy treatment gap in a high gap country

Healthcare systems in many low income countries have evolved to provide services for acute, infections and are poorly structured for the provision of chronic, non-communicable diseases which are increasingly common. Epilepsy is a common chronic neurologic condition and antiepileptic drugs are affordable, but the epilepsy treatment gap remains >90% in most African countries. The World Health Organization has recently released evidence-based guidelines for epilepsy care provision at the primary care level. Based upon these guidelines, we estimated all direct costs associated with epilepsy care provision as well as the cost of healthcare worker training and social marketing. We developed a model for epilepsy care delivery primarily by primary healthcare workers. We then used a variety of sources to develop cost estimates for the actual implementation and maintenance of this program being as comprehensive as possible to include all costs incurred within the health sector. Key sensitivity analyses were completed to better understand how changes in costs for individual aspects of care impact the overall cost of care delivery. Even after including the costs of healthcare worker retraining, social marketing and capital expenditures, epilepsy care can be provided at less than $25.00 per person with epilepsy per year. This is substantially less than for drugs alone for other common chronic conditions. Implementation of epilepsy care guidelines for patients receiving care at the primary care level is a cost effective approach to decreasing the epilepsy treatment gap in high gap, low income countries.

Childhood epileptic seizures imitating migraine and encephalitis

Paroxismal events can resemble epileptic seizures, however, some epileptic seizures, especially benign occipital childhood epilepsies can imitate migraine, cycling vomiting or encephalitis. The aim of this study was evaluation of clinical and electroencephalographic (EEG) features and outcome in children with benign occipital childhood epilepsies. Investigation included 18 patients with benign occipital childhood epilepsies hospitalized in the period from 2007 to 2010. The diagnosis was based on clinical and EEG characteristics of seizures, while treatment included acute therapy for seizures and chronic antiepileptic drugs. Prognosis was analyzed in terms of neurological outcome and seizure recurrence rate. Benign occipital childhood epilepsy with early onset was diagnosed in 15 children. Vegetative symptoms, mostly ictal vomiting (13), eye deviation and loss of consciousness (13) dominated in the clinical presentation. The most frequent EEG findings showed occipital epileptic discharges. Benign occipital childhood epilepsy with late onset was diagnosed in three cases. Seizures were manifested by visual hallucinations, headache and secondary generalized convulsions. All three patients were administered chronic antiepileptic drugs and had good outcome. In our patients, clinical manifestations of benign occipital epilepsies had some similarities with clinical features of migraine and encephalitis. It could explain misdiagnosis in some of them. Knowledge about main features and differences between each of these disorders is crucial for making appropriate diagnosis.

Effect-site Concentration of Propofol Target-controlled Infusion at Loss of Consciousness in Intractable Epilepsy Patients Receiving Long-term Antiepileptic Drug Therapy

Propofol dose requirement for loss of consciousness (LOC) in epilepsy patients would be probably affected by increasing factors [development of tolerance, up-regulated γ-aminobutyric acid (GABAA) receptors, or antiepileptic activity of propofol] and reducing factors [synergistic interaction between propofol and antiepileptic drugs (AEDs) or reduced neuronal mass in cortex] in complex and counteracting ways. Therefore, we determined the effect-site concentration (Ce) of propofol for LOC in intractable epilepsy patients receiving chronic AEDs in comparison with non-epilepsy patients. Nineteen epilepsy patients receiving long-term AEDs therapy and 20 non-epilepsy patients, with the age of 20 to 65 years, were enrolled. The epilepsy patients took their prescribed AEDs until the morning of the operation. Ce of propofol for LOC was determined with isotonic regression method with bootstrapping approach following Dixon's up-and-down allocation. The study was carried out before surgical stimulation. Isotonic regression showed that estimated Ce50 and Ce95 of propofol for LOC were lower in epilepsy group [2.88 μg/mL (83% confidence interval, 2.82-3.13 μg/mL) and [3.43 μg/mL (95% confidence interval, 3.28-3.47 μg/mL)] than in non-epilepsy group [3.38 μg/mL (83% confidence interval, 3.17-3.63 μg/mL) and 3.92 μg/mL (95% confidence interval, 3.80-3.97 μg/mL)] with bootstrapping approach. Mean Ce50 of propofol of epilepsy group was also lower than that of non-epilepsy group without statistical significance (2.8240.19 μg/mL vs 3.16±0.38 μg/mL, P=0.056). For anesthetic induction of epilepsy patients with propofol target-controlled infusion, Ce may need to be reduced by 10% to 15% compared with non-epilepsy patients.