Type Of Antiepileptic Drugs Research Articles

Initial Treatment Retention in Psychogenic Non-Epileptic Seizures

This study investigated whether initial adherence to treatment in psychogenic epileptic seizures differed on the basis of mental health treatment modality and which subject characteristics were predictive of adherence. Initial adherence rates were 54% for combined treatment conducted in the same institution (integrated intervention) and 31% for psychotherapy and psychiatric management offered in different settings (divided intervention). Cognitive complaints and current exposure to antiepileptic drugs (AEDs) were more common among nonadherent patients, and being married (or having a live-in partner) was more common among adherent patients. A predictive model using the mentioned variables (intervention type, marital status, cognitive complaints, and concurrent use of AEDs) showed that this set of variables was predictive of adherence. Marital status and cognitive complaints were the significant contributors to prediction of adherence in the model.

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study.

Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

Self reported adverse effects of mono and polytherapy for epilepsy

PurposeAdverse effects of anti epileptic drugs (AEDs) can significantly affect the life of people with epilepsy. We used a register to determine if polytherapy with AED has more adverse effects than monotherapy. MethodsWe established a register for people with epilepsy (www.UKAED.info). Participants were requested to complete the Liverpool Adverse Event Profile (LAEP) to quantify adverse effects. We also recorded type of epilepsy, seizure control and AED including drug doses. Five hundred and seventy six complete data sets were available, monotherapy (n=186), polytherapy (n=325) and control subjects not taking AED (n=65). ResultsThe mean LAEP scores in polytherapy (45.56, confidence interval (CI)=44.36–46.76) were significantly higher than the mean LAEP scores in monotherapy (42.29, CI=40.65–44.02) and the mean LAEP scores in controls (33.25, CI=31.05–35.44). Tiredness, memory problems and difficulty concentrating were the most common symptoms in patients taking AED and were consistently higher in polytherapy than in monotherapy. Tiredness was reported as always or sometimes being a problem in (polytherapy/monotherapy/controls) 82.5%/75.6%/64.6%, memory problems in 76%/63.2%/29.2% and difficulty concentrating in 68%/63.9%/30.8%. The proportion of seizure-free patients was significantly lower in the polytherapy group (17%) than in the monotherapy group (55%). Depression rates between the monotherapy and polytherapy groups were similar. Drug dosages were higher in polytherapy, however this did not reach statistical significance. ConclusionPatients on polytherapy had significantly higher LAEP scores than patients on monotherapy. This should be carefully discussed with the patient before a second AED is added.

Postponing the morning dose of AEDs: effect on the epileptiform EEG activity

The effects of postponing the morning dose of antiepileptic drugs (AEDs) before undergoing an electroencephalogram (EEG) on the likelihood of recording interictal epileptiform activity (IEA) in patients with epilepsy are unclear. This was a prospective study on patients undergoing video-EEG monitoring. The 3-h recordings used for evaluation started at 08:00 am. Each subject received the usual AED dosage at 08:00 am on the first full day of recording but not until 11:00 am on the following day. IEA (spikes, sharp waves, and spike and wave complexes) was counted at 1-h intervals on each day and compared. Each subject served as his/her own control. The measureable serum drug levels were obtained at 10:00 am on both days. Fifty patients (age 32 ± 11.7 years, 22 women) were enrolled. Forty-seven had focal epilepsy, and three had generalized epilepsy. Six were on monotherapy, and 44 were on polytherapy. The number of IEAs w/wo medication was similar throughout each hour. Twenty-five patients had IEA on the 1st day, and 28 had IEA on the 2nd day. Twenty-one had IEA on both days, while 18 had none on either day. Seven of the 25 without IEA on the 1st day had IEA on the 2nd day, and 4 of the 25 with IEA had no IEA on the 2nd day. Age, gender, epilepsy type, disease duration, seizure frequency, and AED type did not influence IEA. Delaying the morning dose of AEDs prior to an EEG tracing was not associated with increased IEA in patients with epilepsy.

The effect of antiepileptic drugs on coagulation and bleeding in the perioperative period of epilepsy surgery: The Cleveland Clinic experience

Antiepileptic drugs (AED) are known to cause coagulation disturbances. We retrospectively analyzed the effect of AED on coagulation parameters in children who underwent craniotomy for epilepsy surgery. A total of 84 children were included. Perioperative coagulation parameters, the number and type of AED, estimated blood loss and the amount of blood products transfused were recorded. The most commonly used AED was lamotrigine. Of all patients, 7.1% were taking valproate. None of the patients showed significantly abnormal prothrombin time, activated partial thromboplastin time, or platelet count preoperatively. Thirty-eight percent of patients were transfused with allogeneic red blood cells and 4.7% of all patients showed significant coagulopathy intraoperatively and postoperatively. We concluded that the number of AED does not appear to be associated with preoperative coagulation disorders or blood transfusion requirements. However, caution should be taken in patients taking AED who undergo complex brain epilepsy surgery due to the potential for significant blood loss.

Secondary Corpus Callosum Abnormalities Associated with Antiepileptic Drugs in Temporal Lobe Epilepsy

Epilepsy is more than a grey-matter disorder affecting large white matter connections of the brain with seizure generation and propagation. The mechanism for such changes remains unclear. The purpose of this study was to investigate the microstructural changes in the corpus callosum in temporal lobe epilepsy (TLE) patients and whether these abnormalities are related to antiepileptic drug (AED) therapy. Ten TLE patients receiving AED therapy, ten TLE patients with no therapy and ten controls were included in the study. The regions of interest in the corpus callosum were outlined to each Witelson region (WR). Fractional anisotrophy (FA), apparent diffusion coefficient (ADC), three main diffusivity values (λ1, λ2, λ3) and tractography were acquired from each WR. DTI indices of these tracts and each WR were compared between the three subject groups and correlates examined with clinical variables that included duration of epilepsy, gender, AED type and AED therapy exposure. In TLE subjects with receiving AED therapy significantly (p<0.05) decreased FA and increased ADC values of corpus callosum were obtained when compared to the other groups. There was no significant relationship between AED type and DTI indices. Analysis of eigen values in the splenium of corpus callosum (WR7) showed λ1 values were significantly decreased in relation to AED medication duration (p<0.05). FA values of rostrum and corpus showed a reduction with duration of epilepsy. TLE is associated with abnormal integrity of corpus callosum white matter tracts. AED therapy may cause additional damage on secondary degeneration and medication time effects especially on the splenium of corpus callosum.

Epilepsy: fractures and the role of cumulative antiepileptic drug load

An association between antiepileptic drugs (AEDs), low bone mineral density (BMD), fractures, and abnormalities in bone metabolism has been suggested for a longer period, although conclusive evidence has not been reported. We aimed at studying patient characteristics in a high-risk population. All adult patients from a residential unit of a tertiary epilepsy center who were diagnosed with osteoporosis and consequently treated with a bisphosphonate at that moment were included. Correlations between reported fractures and patient characteristics were explored. Of the total population of 261 adult patients, 54 patients were included resulting in a high prevalence rate of 21% osteoporosis in this population. The number of fractures correlated significantly with ambulatory status (r = -0.269, P = 0.05), drug load (r = 0.286, P = 0.04), and current number of AEDs (r = 0.283, P = 0.04). Correlations could not be provided for individual drugs in our population as only a minority was on monotherapy and even less patients had always been on monotherapy of the same antiepileptic drug. Linear regression analysis showed that cumulative drug load (defined by a surrogate parameter: the total duration of epilepsy multiplied by the number of AEDs) was the dominant factor explaining the occurrence of fractures. In this high-risk population, we obtained a positive and strong correlation between the occurrence of fractures in a diagnosed population with osteoporosis and the cumulative drug load of AEDs. This effect seems general, independent of the type of AEDs that were used.

Treatment Factors Affecting Longitudinal Quality of Life in New Onset Pediatric Epilepsy

Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

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

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. 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. 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 > or =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). 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.

Seizure Outcomes Following the Use of Generic versus Brand-Name Antiepileptic Drugs

The automatic substitution of bioequivalent generics for brand-name antiepileptic drugs (AEDs) has been linked by anecdotal reports to loss of seizure control. To evaluate studies comparing brand-name and generic AEDs, and determine whether evidence exists of superiority of the brand-name version in maintaining seizure control. English-language human studies identified in searches of MEDLINE, EMBASE and International Pharmaceutical Abstracts (1984 to 2009). Randomized controlled trials (RCTs) and observational studies comparing seizure events or seizure-related outcomes between one brand-name AED and at least one alternative version produced by a distinct manufacturer. We identified 16 articles (9 RCTs, 1 prospective nonrandomized trial, 6 observational studies). We assessed characteristics of the studies and, for RCTs, extracted counts for patients whose seizures were characterized as 'controlled' and 'uncontrolled'. Seven RCTs were included in the meta-analysis. The aggregate odds ratio (n = 204) was 1.1 (95% CI 0.9, 1.2), indicating no difference in the odds of uncontrolled seizure for patients on generic medications compared with patients on brand-name medications. In contrast, the observational studies identified trends in drug or health services utilization that the authors attributed to changes in seizure control. Although most RCTs were short-term evaluations, the available evidence does not suggest an association between loss of seizure control and generic substitution of at least three types of AEDs. The observational study data may be explained by factors such as undue concern from patients or physicians about the effectiveness of generic AEDs after a recent switch. In the absence of better data, physicians may want to consider more intensive monitoring of high-risk patients taking AEDs when any switch occurs.

Cognitive assessment in patients with epilepsy using the Community Screening Interview for Dementia

Epilepsy is the most common neurological disease worldwide. It may be complicated by cognitive impairments with consequent deleterious effects on education, vocation, and social and family life of affected individuals. We assessed the cognitive functions of Nigerian patients with epilepsy using the modified Community Screening Interview for Dementia (CSID) questionnaire. Eighty-two subjects (41 patients with epilepsy and 41 normal controls) participated in the study. The CSID was used to assess language, memory, orientation, attention, calculation, and praxis. The SPSS statistical package was used for data analysis. The mean ages (in years) of patients with epilepsy and controls were 28.32+/-9.22 and 25.98+/-7.72, respectively. The patients with epilepsy performed poorly when compared with the controls (P<0.05) in the domains Language, Memory, Attention and Calculation, and Praxis, whereas there was no statistically significant difference between the patients and controls in Orientation scores. Duration of epilepsy and of antiepileptic drug (AED) therapy had a significant negative impact on all domains of the CSID (P<0.05), whereas type of AED used did not. The CSID had a sensitivity of 91.7%. This study showed that patients with epilepsy have significant cognitive impairments compared with controls, and duration of epilepsy and AED therapy have deleterious effects on their cognitive performance. In addition, the CSID has acceptable sensitivity and predictive value. It is recommended that cognitive function assessment should be an integral part of routine evaluation of patients with epilepsy.

Interictal spikes on intracranial recording: Behavior, physiology, and implications

The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes. Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24-h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24-h intervals. Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24 h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase. These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.

Antiepileptic drug utilization in children from 1997–2005—a study from the Netherlands

To investigate the utilization of antiepileptic drugs (AEDs) in Dutch children and compare this with guidelines on the treatment of epilepsy in children. From the Dutch Interaction Database (IADB.nl) we selected children aged 0-19 years who received at least one prescription for an AED (ATC-code beginning with N03A) between 1997 and 2005. We calculated cumulative incidences and prevalences per 1000 children per year, stratified by age-category, sex and type of AED, and the total number of months each patient received at least one prescription of AEDs, and we counted the number of person-months and AEDs prescribed. For each AED, proportions of person-months were calculated for mono- and combination therapy. Kaplan-Meier survival analysis was used to analyse the duration of AED use, stratified by sex. The overall prevalence of the prescription of AEDs to children was constant at approximately 4.0 per 1000 children during the years of the study. The overall cumulative incidence from 1997-2005 was 0.67 per 1000 children. When stratified by age category or sex, there were no relevant differences in incidence or prevalence. Valproic acid was the most frequently prescribed drug, followed by carbamazepine and lamotrigine. In 20.3% of all person-months, patients received combination therapy; of these, 34.2% received combination therapy for 3 person-months or less. The older AEDs were prescribed more often as monotherapy than combination therapy, in contrast with the newer AEDs, for which the opposite was true. The 50% survival probability (= time period when 50% of children had stopped using AEDs) was around 2 years, with a significantly lower discontinuation of treatment for girls than boys (P = 0.04). The overall cumulative incidence of AEDs was determined to be 0.67 per 1000 children, and the prevalence 4.0 per 1000 children. The most frequently prescribed drug is valproic acid, followed by carbamazepine and lamotrigine. The prescribing of AEDs seems to be in conformity with the overall recommendations of the guidelines on the treatment of epilepsy in children.

Exploratory Polysomnographic Evaluation of Pregabalin on Sleep Disturbance in Patients with Epilepsy

To evaluate the effects of adjunctive pregabalin 300 mg/day versus placebo on polysomnographic (PSG) variables in patients with well controlled partial seizures and subjectively reported sleep disturbance. An exploratory, 4-week, double-blind, randomized study in patients with well controlled partial seizures on AED monotherapy and subjective sleep disturbance over the previous 6 months. Mean changes from baseline to endpoint in PSG and subjective sleep variables (MOS Sleep Scale, Groningen Sleep Questionnaire) in patients on adjunctive pregabalin 300 mg/day (n=8) were compared with patients on placebo (n=7). Baseline PSGs showed sleep fragmentation. Mean sleep efficiency improved significantly in both treatment groups in the mean baseline to endpoint change; there was no significant between-group difference. Pregabalin treatment was associated with a significant reduction in number of awakenings (p = 0.02), and improvement in wake time after sleep onset approached significance (p = 0.055), suggesting improvement in sleep continuity that was not observed in the placebo group. Pregabalin was also associated with significant improvements in the MOS sleep disturbance and sleep quantity subscales compared with placebo (p < or =0.03). There were no changes in self-reported seizure control. This exploratory pilot study suggests that pregabalin may improve sleep continuity in patients with clinically relevant sleep disturbance. The effect on disturbed sleep appears independent of seizure control. The effects of pregabalin on disturbed sleep and seizures and their interrelationships warrant further study.

Rapid versus slow withdrawal of antiepileptic drugs

The ideal objective of treating a person with epilepsy is to induce remission by usage of antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term side effects. Hence when a person with epilepsy is in remission (free of seizures for some time) it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review proposes to examine the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on recurrence of seizure. This review also examines the effect of variables such as age of seizure onset, seizure types, presence of neurological deficits, mental subnormality, aetiology of epilepsy, type of AED, EEG findings or duration of seizure freedom on the risk of recurrence of seizures with the two tapering regimens. (1) To quantify risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period or more than three months) discontinuation of antiepileptic drugs in adults with epilepsy who are in remission. (2) To quantify the risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period of more than three months) discontinuation of antiepileptic drugs in children with epilepsy who are in remission. (3) To attempt to assess which variables modify the risk of seizure recurrence. We searched the Cochrane Epilepsy Group's Specialized Register (August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2004) and cross-references from identified studies. No language restrictions were imposed. Randomized controlled trials that evaluate withdrawal of AEDs in a rapid or slow manner after varying periods of seizure control in patients with epilepsy. Both review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure relapse (i.e. the percentage of patients experiencing seizure recurrence after withdrawal of AED); time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure such as injuries, fractures, aspiration pneumonia; and quality of life (if assessed by validated scale). One trial with weak methodology involving 149 children was included with a mean age of seizure onset of four years, mean age of 11 years at the time of starting the taper. The rapid taper group (six weeks) recruited 81 participants and the slow taper group (nine months) included 68 participants, out of whom 11 and 5 were lost to follow up even before the taper began respectively. The number of participants who were seizure free in the rapid and slow taper groups were 40 and 44 respectively at the end of one year follow up (OR 0.53, 95% CI 0.27 to 1.03); 30 and 29 respectively at the end of two years, (OR 0.79, 95% CI 0.41 to 1.53); 24 and 14 respectively at the end of three years (OR 1.62, 95% CI 0.76 to 3.46); 18 and 8 respectively at the end of four years (OR 2.14, 95% CI 0.87 to 5.3); 10 and 6 respectively at the end of five years (OR 1.46, 95% CI 0.5 to 4.23). In view of methodological deficiencies and small sample size, in the solitary study identified, we cannot derive any reliable conclusions regarding the optimal rate of tapering of AEDs. Further studies are needed in adults as well as in children to investigate the rate of withdrawal of AEDs and to study the effects of variables such as seizure types, its aetiology, mental retardation, EEG abnormalities, presence of neurological deficits and other co-morbidities on the rate of tapering.

The Use of Lamotrigine and Other Antiepileptic Drugs in Paediatric Patients at a Malaysian Hospital

(1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs). A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang. Seizure frequency, cost of drug and types of AED prescribed. A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00). The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

Vagus nerve stimulation for epilepsy

In two prospective, double-blind, 3-month trials with 300 patients, chronic intermittent high intensity electrical stimulation of the cervical vagus nerve with a subcutaneous surgically implanted device (vagus nerve stimulation, VNS) reduced medication-resistant partial onset seizures by 24–28%, compared with seizure rate reductions of 6–15% in the low intensity control group. Side effects in the first 3 months of treatment were hoarseness (60%), cough (38%), parasthesias (20%) and dyspnea (20%); after 3 years of VNS, less than 5% of patients experience side effects. Seizure rates decline further with increasing VNS treatment durations (43% of patients have a 50% or more seizure rate reduction after 3 years); this seems independent of later antiepileptic drug (AED) and stimulation parameter changes. Antiepileptic effects of VNS may persist after termination of the therapy. The following clinical features are not predictive of seizure rate responsiveness to VNS: epilepsy duration, epilepsy syndrome, age, gender, epilepsy onset age, baseline seizure rate, prior epilepsy surgery, number and type of concomitant AEDs, number of prior AEDs, and number of seizure types. In one small study, increased thalamic blood flow seen on PET scans performed upon VNS initiation was predictive of later clinical responsiveness. Better methods to identify preoperatively probable VNS responders need to be developed.

Impact of New-Generation Agents on Antiepileptic Drug Prescribing Patterns in a Residential ICF-MR Facility

Describe the impact of newer antiepileptic drugs (AEDs) on prescribing practices in a large, residential intermediate-care facility for the mentally retarded (ICF-MR), with onsite clinical pharmacist support services, over a 15-year period. All residents at the facility receiving AEDs for management of seizure disorder were included in this retrospective assessment. Number and type of AEDs used per individual were recorded and analyzed over the 15-year interval. Current prescribing practices were evaluated regarding rational polytherapy prescribing trends. 400-bed residential ICF-MR for the severe to profoundly mentally retarded. All individuals residing at the ICF-MR facility receiving AED therapy for a seizure disorder. Residents were primarily in the severe to profound range of developmental disability, with multiple medical comorbidities. Clinical pharmacists actively participate in all treatment teams and monthly neurology clinic to promote and encourage rational pharmacotherapy. Prescribing trends related to AED therapy were followed over a 15-year period. Comparisons were made regarding monotherapy and polytherapy at multiple-year intervals, with specific emphasis on how the newer generation AEDs have affected use of older medications. Overall trend from 1988 suggests more monotherapy and less use of barbiturates. Introduction of a new generation of AEDs has not affected the overall trend toward one- or two-drug regimens over the period in review. The relative stability of the number of AEDs per resident during the introduction of a new generation of AEDs suggests that as new drugs are added, ineffective or problem-prone drugs are discontinued.

Pathophysiology of bone loss in patients receiving anticonvulsant therapy

Many studies have shown that patients taking antiepileptic drugs (AEDs) are at increased risk for metabolic bone disease and low bone mineral density. Although early reports of bone disease in patients with epilepsy often involved institutionalized patients, who may be at risk because of lack of physical activity, reduced sunlight exposure, and poor nutrition, low bone density has also been reported in well-nourished, ambulatory outpatients with epilepsy. Traditionally, attention to the problem of AED-induced bone loss has been focused on those drugs that induce the hepatic cytochrome P450 enzyme system, thereby increasing the metabolism of vitamin D. However, the mechanisms of AED-induced bone loss appear to be multiple, and all types of AEDs are potentially implicated. Besides hepatic enzyme induction, mechanisms may include direct effects of AEDs on bone cells, resistance to parathyroid hormone, inhibition of calcitonin secretion, and impaired calcium absorption. An understanding of bone biology and the pathophysiology of bone loss can aid in the identification and monitoring of patients at risk and in the planning of appropriate prophylactic and therapeutic measures, by which most of the morbidity associated with AED-induced bone loss can be prevented.

AED Effects on Bone Density.

AED Effects on Bone Density.