Antiepileptic drugs (AEDs)

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Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

In human medicine, a plethora of new antiepileptic drugs (AEDs) have been developed over the years for use either as monotherapy or adjunctive therapy [1]. Many of these drugs are now also used in veterinary medicine. This has led to an increase in the arsenal of AEDs used to treat canine epilepsy. As a rule, AEDs are evaluated on the grounds of their effectiveness and safety through clinical trials and experimental laboratory studies before they are approved for use in patients by the regulatory authorities, e.g. the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) [2]. The safety profile of drugs is an important consideration for their approval by the authorities and use by prescribing clinicians on their clients’ animals [2, 3]. It affects clinicians’ decisions to prescribe specific AED(s), as serious adverse effects can lead to chronic complications or even death. Less serious, but none- theless important, adverse effects can significantly im- pact quality of life, leading to systematic illness which may increase the overall cost of treatment [3, 4]. Ultimately, the benefits of an effective AED may be outweighed by its adverse effects, and the latter should be always taken into consideration.
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Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence

Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence

Abstract: Two years after the warning issued by the Food and Drug Administration on an increased risk of suicide for people taking antiepileptic drugs (AEDs), a number of pharma- coepidemiologic studies have been published but the scientific community is far from definitive answers. The present paper is aimed at reviewing available evidence on the association between AEDs and suicidal behavior, discussing major variables involved such as the relationship between epilepsy, depression, and suicide and the psychotropic potential of AEDs. All studies published so far show a lack of concordance and are constrained by various methodological limitations. What seems to be established is that mood disorders represent a frequent comorbid- ity in epilepsy and suicide is a serious complication more frequently encountered in epilepsy rather than in the general population. Moreover, a subgroup of patients appears to be at risk of developing treatment-emergent psychiatric adverse effects of AEDs independently of the specific mechanism of action of the drug. The prior history of suicide attempt, especially pre- ceding the onset of the epilepsy, may represent a key element explaining why what is observed is independent of the specific mechanism of the drug. In general terms, risks associated with stopping, or not even starting, AEDs in epilepsy might well be in excess of the risk of suicide in epilepsy, as deaths due to accident and epilepsy itself may predominate. Clinicians need to pay attention not only to seizure patterns when choosing the appropriate AED but also to a number of different parameters (eg, age, gender, working needs, medical comorbidities, history of psychiatric disorders, and suicidality before epilepsy onset) and not the least the mental state of the patient. Missing severe complications such as suicidal behavior or delaying its treatment may worsen the prognosis of epilepsy.
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Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

All in all, however, the existence of a relationship between estrogen biosynthesis and epilepsy is unmistak- able, and scientific evidence exists to prove that all forms of epilepsy may indeed have this common origin [17]. Regardless, the set of current antiepileptic drugs and the set of known aromatase inhibitors certainly have several, if not many, compounds in common. Similarly, screening for potential AIs could lead to the identification of poten- tial AEDs, as well. The focus of this study, therefore, is to demonstrate this and to further analyze the common features among AIs and AEDs in an effort to prove their chemical and structural similarity.
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Assessing suicidal risk with antiepileptic drugs

Assessing suicidal risk with antiepileptic drugs

Abstract: Recently, the US Food and Drug Administration issued an alert about an increased risk for suicidality during treatment with antiepileptic drugs (AEDs) for different indications, including epilepsy. We discuss the issue of suicide in epilepsy with special attention to AEDs and the assessment of suicide in people with epilepsy. It has been suggested that early medical treatment with AEDs might potentially reduce suicide risk of people with epilepsy, but it is of great importance that the choice of drug is tailored to the mental state of the patient. The issue of suicidality in epilepsy is likely to represent an example of how the underdiagnosis of psychiatric symptoms, the lack of input from professionals (eg, psychologists, social workers, and psychiatrists), and the delay in an optimized AED therapy may worsen the prognosis of the condition with the occurrence of severe complications such as suicide.
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Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy

Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy

Purpose: To evaluate the effect of antiepileptic drugs (AEDs) on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for 1 year. Thirty- four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford- Binet (4th edition), Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.
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The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

Epilepsy is considered the most important risk factor for long-term disability in brain tumour patients [23]. Unfor- tunately, the side effects related to antiepileptic drugs can seriously affect the patients' quality of life; in fact, it has been found that patients' concerns with the AEDs' side effects have often taken precedence over their desire to reduce seizure frequency [24]. Side effects are mostly asso- ciated with the administration of traditional, older AEDs [3-8]. The few studies which have been done on the newer AEDs indicate that these same side effects are less frequent with these drug [9-13]. To date, a comparative study of this type has not been done.
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Antiepileptic Drugs and Suicide: The Light at the End of the Tunnel

Antiepileptic Drugs and Suicide: The Light at the End of the Tunnel

OBJECTIVE: Because some recent studies suggest increased risk for suicide-related behavior (SRB; ideation, attempts) among those receiving antiepileptic drugs (AEDs), we examined the temporal relationship between new AED exposure and SRB in a cohort of older veterans. METHODS: We used national Veterans Health Administration databases to iden- tify veterans aged ≥65 years who received a new AED prescription in 2004–2006. All instances of SRB were identified using ICD-9-CM codes 1 year before and after the AED exposure (index) date. We also identified comorbid conditions and medication associated with SRB in prior research. We used generalized estimating equations with a logit link to examine the association between new AED exposure and SRB during 30-day intervals during the year before and after the index date, controlling for potential confounders. RESULTS: In this cohort of 90,263 older veterans, the likelihood of SRB the month prior to AED exposure was significantly higher than in other time periods even after adjusting for potential confounders. Although there were 87 SRB events (74 individuals) the year before and 106 SRB events (92 in- dividuals) after, approximately 22% (n = 16) of those also had SRB before the index date. Moreover, the rate of SRB after AED start was gradually reduced over time. CONCLUSIONS: The temporal pattern of AED exposure and SRB suggests that, in clinical practice, the peak in SRB is prior to exposure. While speculative, the rate of gradual reduction in SRB thereafter suggests that symptoms may prompt AED prescription.
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Effect of antiepileptic drugs on cognitive functions in school going children with epilepsy

Effect of antiepileptic drugs on cognitive functions in school going children with epilepsy

The reasons for the cognitive impairment are multifactorial but besides primary brain pathology, certain factors like age at onset of seizure, seizure type and antiepileptic drugs (AEDs) have been observed to be closely associated with cognitive dysfunction and behavioural disturbances, although it is often difficult to determine the relative contribution of any given factor - as emphasized by Mitchel et al., 1991 8 .

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Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Background: Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs ’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total.
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Antiepileptic drugs and breastfeeding

Antiepileptic drugs and breastfeeding

Breastfeeding is known for its beneficial effects on both mothers and infants [1,2]. Nevertheless, in mothers suf- fering from epilepsy or bipolar disorders treated with antiepileptic drugs (AEDs), some concerns on infant health may raise. The decision to encourage breast- feeding in those women should be taken after a careful evaluation of the possible side-effects on the infant caused by the indirect exposure to AEDs via breast milk. Data on the use of AEDs by the nursing woman are mainly represented by single pharmacologic or pharma- cokinetic studies and/or by case reports or case series on the side-effects attributed to their presence in breast milk. Moreover, toxicological and clinical data on AEDs during breastfeeding are dispersed in the scientific litera- ture and consequently not easily accessible to health professionals called to give an evidence-based clinical advice. The present paper aims at providing the clinician with an updated synopsis of the lactation risk of AEDs.
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Influence of conventional antiepileptic drugs on glutathione-S-transferase and lipid peroxidation in children with idiopathic epilepsy

Influence of conventional antiepileptic drugs on glutathione-S-transferase and lipid peroxidation in children with idiopathic epilepsy

Background: Evidence suggests that conventional antiepileptic drugs (AEDs) change the oxidative-antioxidative balance in epileptic children, so our aim of this study to evaluate the influence of the conventional AEDs valproic acid (VPA), carbamazepine (CBZ), or both on antioxidant enzyme activity and lipid peroxidation in epileptic children. Methods: Fifty patients with idiopathic epilepsy and twenty five healthy children serving as controls were included in the study. The epileptic children were further subdivided into three subgroups according to drug therapy: group A, twenty patients treated with VPA; group B, twenty patients treated with CBZ; and group C, ten patients treated with both drugs. Malondialdehyde (MDA) and glutathione-S-transferase (GST) levels were measured in the patients and controls. Results: The GST level was significantly lower in the patients than that in the controls ( p < 0.001), while the MDA level was significantly higher in the patients than that in the controls ( p < 0.001). The duration of drug intake was negatively correlated with the GST level and positively correlated with the MDA level in the three epileptic patient groups. Conclusion: The oxidant-antioxidant balance is disturbed in epileptic children who receive VPA, CBZ, or both.
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A prospective study of adverse drug reactions to antiepileptic drugs in children

A prospective study of adverse drug reactions to antiepileptic drugs in children

Most children in this study received monotherapy, with only 25% receiving polytherapy. Monotherapy for epilepsy became standard management in the 1970s as it was recognised that polytherapy was more likely to be associated with drug toxicity. 29 AED used as monother- apy is effective in 60 – 70% of children. 25 27 30 Additional drugs in refractory patients have been shown to be only marginally bene fi cial. 31 32 Polytherapy is associated with a greater risk of drug toxicity in paediatric patients in general, 18 33 especially those receiving AEDs. 34 More children receiving polytherapy in this study developed ADRs, with up to a threefold higher incidence of ADRs compared to monotherapy. Unfortunately, most new Table 3 Adverse reactions to antiepileptic drugs
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Effect of various antiepileptic drugs in zebrafish PTZ-seizure model

Effect of various antiepileptic drugs in zebrafish PTZ-seizure model

The test was conducted in zebrafish placed individually in black boxes, which contained different concentrations (2, 4, 6 and 8 mM) of PTZ solution (1 l). Another set of black boxes contained the mixture of solution of PTZ 6 mM and the different concentrations of antiepileptic drugs (AEDs). Tests were conducted separately for each AED and PTZ combination in a different set of black boxes. During the test, fish were observed for the onset of different types of seizures by a trained blind observer. The time latencies from start of fish exploration in the bath medium to the appearance of stage I (characterised by increase swim activity), stage II (characterised by the rapid whirlpool-like circling swim behaviour) and
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The Use of Blood Levels of Antiepileptic Drugs in Clinical Practice

The Use of Blood Levels of Antiepileptic Drugs in Clinical Practice

The Use of Blood Levels of Antiepileptic Drugs in Clinical Practice.. Henn Kutt, M.D.[r]

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SPECIAL ARTICLE Managing Pediatric Epilepsy Syndromes With New Antiepileptic Drugs

SPECIAL ARTICLE Managing Pediatric Epilepsy Syndromes With New Antiepileptic Drugs

ABSTRACT. The management of epilepsy in the pedi- atric patient requires careful evaluation, classification, and pharmacologic treatment. Despite best efforts on the part of clinicians, approximately 25% of children remain refractory to appropriate medical therapies. The develop- ment of an improved classification system and the emer- gence of several new antiepileptic drugs have enabled some progress in this area, specifically in children with disorders such as Lennox-Gastaut syndrome and infan- tile spasms, which are notoriously difficult to control. However, limited data are available that define the opti- mal use of new antiepileptic agents in pediatric patients. To most effectively treat children with epilepsy syn- dromes, further research must be completed to validate the positive effects described in case reports, open-label clinical trials, and early controlled clinical trials. Pediatrics 1999;104:1106 –1116; epilespy, pediatrics, anti- epileptic drugs.
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Effect of Antiepileptic drugs on Psychomotor Functions and Memory in Epilepsy Patients

Effect of Antiepileptic drugs on Psychomotor Functions and Memory in Epilepsy Patients

Objective: The present study was designed to compare the effect of various antiepileptic drugs on psychomotor and memory function in epileptic patient and to compare them with normal human volunteer. Material & Methods: It was cross-sectional case control study with a total of 30 cases and 30 controls. All 30 patients were diagnosed cases of Generalised Tonic Clonic Seizure (GTCS) and were on antiepileptic drugs for more than one year. Comparison of patients for all psychomotor tests with the normal subjects matching in age, gender and education was done using unpaired t test. Results: In all the test patients performed poor compared to control group and the difference was significant (p<0.05) for Digit letter substi- tution test, Choice reaction time (audio and video) where as it was very significant (p<0.01) for Critical flicker fusion test and PGI Memory Scale. In Six-letter cancellation test and Hand steadiness test also patients performed poor compared to subjects but difference was not significant. A further comparison of all the tests was done between patients on mono- therapy and polytherapy. PGI Memory scale showed significantly (p<0.05) inferior memory of patients on polytherapy as compared to monotherapy. In all other psychomotor tests also patients on monotherapy had better score compared to polytherapy but differences were not significant. Conclusion: Thus we conclude there is definitely a deterioration of psycho- motor and memory with use of antiepileptic drugs.
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Effects of Longterm Antiepileptic Drugs on Vascular Risk Factors and Atherosclerosis.

Effects of Longterm Antiepileptic Drugs on Vascular Risk Factors and Atherosclerosis.

I hereby solemnly declare that this dissertation titled “Effects Of Longterm Antiepileptic Drugs On Vascular Risk Factors And Atherosclerosis” was done by me in Institute of Neurology, Madras Medical college and Rajiv Gandhi Government General Hospital, Chennai -3, under the guidance and supervision of Prof. Dr. S. Balasubramanian.MD., D.M., Professor of Neurology, Institute of Neurology, Madras Medical College & Rajiv Gandhi Government General Hospital, Chennai. This dissertation is submitted to the Tamil Nadu Dr. M.G.R. Medical University towards the partial fulfillment of requirement for the award of D.M Degree Branch I (NEUROLOGY).
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DRUG UTILIZATION PATTERN OF ANTIEPILEPTIC DRUGS IN TERTIARY CARE HOSPITAL

DRUG UTILIZATION PATTERN OF ANTIEPILEPTIC DRUGS IN TERTIARY CARE HOSPITAL

Introduction: Drug utilization pattern is useful in the evaluation of the standards of therapy for people suffering with epilepsy and seizures. Drug utilization statistics are an important tool with which we can evaluate the quality of prescribing in a defined setting. Drug utilization pattern can increase understanding the rational drug use in seizures and its outcomes. Aim: To study the drug utilization pattern of antiepileptic drugs in a tertiary care hospital. Methodology: A prospective observational study was conducted for duration of six months in general medicine and pediatric wards of Gandhi hospital. During study period all anti-epileptic cases were collected on regular basis and these cases were analyzed for following results. Results: Age wise distribution shows 2-12 were more prevalent (P value –<0.01), males were more affected. Atypical febrile seizures were found to be highest in infants (P value- < 0.01), in Children GTCS 39.53% (n=17) was found to be highest, in adolescents GTCS, Unclassified seizures, Complex partial seizures, Status epilepticus, Atypical febrile seizures were distributed equally, in adults GTCS was found to be highest (P value- < 0.05). Causes for different type of seizures found that, space occupying lesions were significant cause for GTCS (P value < 0.01) and Infectious causes were significant for Unclassified seizures (P value- < 0.0001), Status epilepticus (P value- < 0.05), Atypical febrile seizures (P value- < 0.05), Simple febrile seizures (P value- < 0.05). Idiopathic cause is significant (P value- < 0.05) for Typical febrile seizures. Simple partial seizures were mostly caused due to Circulatory disturbances (P value- < 0.05). Dual therapy was most frequently used in Atypical febrile seizures, Complex partial seizures, Simple febrile seizures, simple partial seizures and monotherapy was used in GTCS, Unclassified seizures, Status epilepticus. Phenytoin was most commonly used drug in
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Influence of Cimetidine in Combination with Antiepileptic Drugs on Locomotor Activity in Mice

Influence of Cimetidine in Combination with Antiepileptic Drugs on Locomotor Activity in Mice

Day before the experiments, animals were habituated to laboratory procedures and tests began immediately after ip administration of the vehicle. Next day mice were examined under the same conditions. Prior to the test, animals were deprived of food for 24 h. Antiepileptic drugs were administered at doses equal to their ED 50 values against MES-induced seizures. Mice received analysed substances at times scheduled for the electroconvulsive test, according to Swiader et al. [7] .

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Therapeutic Drug Monitoring of Antiepileptic Drugs: Indications and Modalities

Therapeutic Drug Monitoring of Antiepileptic Drugs: Indications and Modalities

2.4.2 In case of changes in distribution: During pregnancy, physiological changes may impact mainly on the distribution of antiepileptic drugs between the mother and the foetus as well as the elimination of antiepileptics [34, 48]. A study was done in a group of 63 epileptic women during childbirth [49]. These patients were taking either lamotrigine alone or in combination with carbamazepine or valproic acid. Blood samples were taken from the mothers and the umbilical cords. The results of this study showed that in case of monotherapy, the umbilical cord/mother concentration ratio was between 0.40 and 1.38, thus showing the degree of passage of lamotrigine from the mother to the foetus. Co-administration of valproic acid led to a significant increase in the lamotrigine concentrations of both the mother and the umbilical cord samples with a significant 65% decrease in the clearance of lamotrigine. With carbamazepine, increased clearance of lamotrigine was not significant, but concentrations of valproic acid and carbamazepine in the umbilical cord were respectively 30% higher and 20% lower than those in the mothers’ samples.
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