- •Behavioral problems (e.g., depression) in epilepsy are common but usually of mild severity.
- •30 AED-sensitive items were discerned from the BDI-I, NDDI-E, and FPZ.
- •Items were classified into six scales, constituting the new screening tool “PsyTrack”.
- •PsyTrack subscale scores differed as a function of drug load and presence of AEDs with negative psychotropic effects.
- •Generally, monotherapy seems to be favorable in terms of behavioral adverse effects.
Posts Tagged antiepileptic drugs
[WEB] How common is Epilepsy?
Posted by Kostas Pantremenos in Epilepsy on April 23, 2024
Epilepsy – An Overview
Epilepsy is not one single condition. Rather, it is defined as a spectrum of disorders that involve abnormal activity within the brain. “Epilepsy” means the same thing as the term “seizure disorders.” In epilepsy, abnormal brain waves disturb electrical activity, leading to seizures. Symptoms of epileptic seizures include having unusual sensations or emotions, behaving in unusual ways, or experiencing convulsions or loss of consciousness. Brain damage, illness, and irregular brain development can all cause abnormal brain waves that lead to seizures.
Approximately half of all people who have had one seizure will have more (typically within six months). However, in order to be diagnosed with epilepsy, a person must have had more than one seizure, and doctors must consider it likely that they will continue to have seizures. When a person has a seizure that lasts for more than 5 minutes, or a person has more than one seizure within a 5 minutes period (without returning to consciousness between the seizures), it is called status epilepticus.
Some forms of epilepsy last for a limited time, although the condition is often lifelong. Although there is no cure currently for epilepsy, there are many treatments available for the condition. About 70 percent of people with seizures can control them with proper diagnosis and use of medication.
There are many different types of seizures, and some people with epilepsy will experience more than one type. Some examples of seizure types include:
- Absence seizures
- Generalized tonic-clonic seizures
- Atonic (or akinetic) seizures
The History of Epilepsy
People have been aware of epilepsy and seizures for millennia. A Babylonian medical textbook made up of 40 tablets and dating to 2000 B.C. contains a chapter that accurately describes many of the different types of seizures known today. However, seizures were thought to be supernatural in cause — each seizure type was associated with a different evil spirit or angry god — so the treatments prescribed were spiritual.
Epilepsy in Ancient Greece
The word “epilepsy” comes from the Greek word “epilepsia,” meaning “to seize” or “to take hold of.” By the 5th century B.C., the Greeks still considered epilepsy a “sacred” disease. Yet the renowned ancient physician Hippocrates described epilepsy as a brain disorder. This was a radical idea for the time. He recommended physical treatments while also recognizing that if the seizures became chronic, the disorder was incurable.
Despite Hippocrates’ writings, epilepsy continued to be considered a supernatural condition for the next two millennia. People with epilepsy were subjects of immense social stigma, treated as outcasts, and even punished as witches. In many places, people who suffered seizures were prevented from going to school, working, marrying, and having children. There were a few people with prominent positions thought to have had epilepsy — including Julius Caesar, Tsar Peter the Great of Russia, Pope Pius IX, and Fyodor Dostoevsky — but most people with epilepsy were prevented from living as full members of society.
Epilepsy in the 14th Century and Beyond
During the Renaissance, some scientists tried to prove epilepsy was a physical, not spiritual, illness. Then, in the 19th century, neurology became a recognized medical discipline and the idea of epilepsy as a brain disorder became normal in North America and Europe. In 1857, Sir Charles Lacock introduced bromide of potassium as the first antiepileptic drug (AED).
In 1873, a British neurologist named John Hughlings Jackson first described epilepsy as we understand it today. Jackson showed that seizures are caused by sudden, brief electrochemical discharges of energy in the brain. In 1909, the International League Against Epilepsy was founded as a global professional organization of epileptologists.
By the 1920s, Hans Berger, a German psychiatrist, had developed the electroencephalogram (EEG) to measure brain waves. It showed that each type of seizure is associated with a different brain wave pattern. The EEG also aided in the discovery that specific sites in the brain were responsible for seizures and expanded the potential for surgical treatments. Surgery became a more widely available option by the 1950s.
The Development of Antiepileptic Drugs
The medication phenobarbital was identified as an AED in 1912, and phenytoin (sold under the brand names Dilantin and Phenytek) was developed in 1938. Carbamazepine (sold under the brand names Tegretol and Carbatrol) was identified in 1953. These drugs have since been approved by the U.S. Food and Administration (FDA) and continue to be used today.
An accelerated drug-discovery process began in the 1970s with the creation of the Anticonvulsant Screening Program, sponsored by the National Institute of Neurological Disorders and Stroke. The program helped scientists gain a better understanding of the brain and epilepsy. Scientists have strived to reduce serious side effects associated with the use of older AEDs through drug-development processes.
Keppra (levetiracetam) was approved by the FDA in 1999. Several newer drugs, including Vimpat (lacosamide), Briviact (brivaracetam), and Aptiom (eslicarbazepine acetate), have been introduced in the past 10 to 15 years. Other promising medications are also in the pipeline.
Social Stigma
The stigma around epilepsy has lessened as more people are able to effectively treat their seizures. However, epilepsy largely remains an “invisible” illness. Millions of people in developing countries do not have access to AEDs, and stigma and discrimination are still widespread, especially in places where people still believe that seizures have a supernatural cause.
How Common Is Epilepsy?
People of all backgrounds, races, ethnicities, and ages are equally affected by epilepsy. It is estimated that epilepsy affects 1.2 percent of the population of the United States and more than 50 million people worldwide, making it one of the most common neurological disorders. Approximately 45,000 children under the age of 18 are diagnosed with epilepsy every year in the U.S., and roughly 10.5 million children worldwide live with epilepsy.
Diagnosing Epilepsy
Neuroimaging capabilities have improved over the past few decades. Magnetic resonance imaging (MRI), computerized tomography (CT) scans, and other techniques are able to detect more and more subtle brain lesions responsible for epilepsy.
Read more about diagnosing epilepsy.
Causes of Epilepsy
Causes of epilepsy include a wide variety of brain-related issues, such as structural damage, infectious diseases (like encephalitis), and genetic anomalies. Risk factors for epilepsy include:
- Age
- A family history of seizures
- Head injuries (such as traumatic brain injury or TBI)
- A history of seizures as a child
Read more about causes of seizures and epilepsy.
Types of Seizures
There are many types of epilepsy. Seizures are broken into two categories: focal seizures and generalized seizures. Focal seizures can be categorized by whether or not there is a loss of consciousness or awareness. Generalized seizures can be further broken down into absence, tonic, atonic, clonic, myoclonic, and tonic-clonic seizures.
Learn more about seizure types and symptoms of epilepsy.
Condition Guide
[ARTICLE] Medication use in poststroke epilepsy: A descriptive study on switching of antiepileptic drug treatment – Full Text
Posted by Kostas Pantremenos in Epilepsy on September 2, 2020
Highlights
- It is unknown why patients switch their antiepileptic drugs in poststroke epilepsy.
- We found that 40% of patients needed to switch.
- 13% of patients switched because of ineffectivity of the first prescribed AED.
- Dosages at the time of switching were higher in case of ineffectivity than in case of side effects.
Abstract
Objective
Currently, as evidence-based guidelines are lacking, in patients with poststroke epilepsy (PSE), the choice of the first antiepileptic drug (AED) is left over to shared decision by the treating physician and patient. Although, it is not uncommon that patients with PSE subsequently switch their first prescribed AED to another AED, reasons for those switches are not reported yet. In the present study, we therefore assessed the reasons for switching the first prescribed AED in patients with PSE.
Method
We gathered a hospital-based case series of 53 adult patients with poststroke epilepsy and assessed the use of AEDs, comedication, and the reasons for switches between AEDs during treatment. We also determined the daily drug dose (DDD) at the switching moment.
Results
During a median follow-up of 62 months (Interquartile range [IQR] 69 months), 21 patients (40%) switched their first prescribed AED. Seven patients switched AED at least once because of ineffectivity only or a combination of ineffectivity and side effects, whereas 14 patients switched AED at least once because of side effects only. The DDD was significantly (p < 0.001) higher in case of medication switches due to ineffectivity (median 1.20, IQR 0.33) compared to switching due to side effects (median 0.67, IQR 0.07). There was no difference in the use of comedication between the group that switched because of ineffectivity compared to the group that switched because of side effects.
Conclusion
In our case series, up to 40% of patients with epilepsy after stroke needed to switch their first prescribed AED, mostly because of side effects in lower dosage ranges.
1. Introduction
Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly [1]. Nevertheless, there are no specific evidence-based guidelines regarding treatment of patients with poststroke epilepsy (PSE). Therefore, the choice of antiepileptic drug (AED) is left over to shared decision by the treating physician and patient. From the 2013 International League Against Epilepsy (ILAE) report on initial monotherapy for epileptic seizures and syndromes, it appears that carbamazepine, levetiracetam, phenytoin, and zonisamide have ‘level A’ evidence for treating focal epilepsy in adults [2, 3, 4, 5]. This may already guide the choice of the AED by mainly effectivity arguments. On the other hand, according to a recent study by Larsson et al., in patients with PSE, retention rates are highest for levetiracetam and lamotrigine, and lowest for carbamazepine and phenytoin [6], meaning that carbamazepine and phenytoin are more often switched to another drug or discontinued. A 2018 review of randomized controlled trials on AED for the treatment of PSE found that levetiracetam and lamotrigine were better tolerated than carbamazepine [7]. However, reasons for discontinuation or switching of AEDs in patients with PSE are not reported. We therefore aimed to study the reasons for switching the first prescribed AED in patients with epilepsy after stroke.[…]
Continue —-> https://www.epilepsybehavior.com/article/S1525-5050(19)30593-1/fulltext
[Abstract] Withdrawal seizures: possible risk factors
Posted by Kostas Pantremenos in Epilepsy on June 17, 2020
Abstract
Introduction
Most of the patients usually achieve seizure freedom under treatment with antiseizure medications (ASMs). Drug withdrawal in seizure-free patients is still one of the most challenging issues in the management of epilepsy. The decision-making process of whether the treatment should be discontinued must be based on the evaluation of possible long-term side effects of chronic treatment and, on the other hand, the risk of seizure relapse.
Areas Covered
This review aims to describe and discuss possible predictors and risk factors for seizure relapse during and after discontinuation, according to the available literature evidence.
The most important risk factors for withdrawal failure are the etiology of the epilepsy syndrome and epilepsy-related factors, worsening or persistence of epileptiform abnormalities on EEG recordings at the time of discontinuation or during drug tapering, and brain MRI abnormalities.
Each single risk factor should be considered together with possible other concurrent predictors.
Expert Opinion
The decision to withdrawal antiseizure medication in seizure-free patients should be carefully planned and based on the evaluation of predictors. A discontinuation program should include tailored discussion with patients and family members and individualized decision, the taper schedule, and plans for monitoring during and after drug tapering.
Links: Antiseizure medications, antiepileptic drugs, withdrawal, discontinuation, seizure relapse, epilepsy syndrome, etiology, electroencephalogram, neuroimaging
Source: https://www.tandfonline.com/doi/abs/10.1080/14737175.2020.1780917?journalCode=iern20
[ARTICLE] Prediction of the Recurrence Risk in Patients With Epilepsy After the Withdrawal of Antiepileptic Drugs – Full Text PDF
Posted by Kostas Pantremenos in Epilepsy on June 12, 2020
Abstract
Many seizure-free patients who consider withdrawing from antiepileptic drugs (AEDs) hope to discontinue treatment to avoid adverse effects. However, withdrawal has certain risks that are difficult to predict. In this study, we performed a literature review, summarized the causes of significant variability in the risk of postwithdrawal recurrent seizures, and reviewed study data on the age at onset, cause, types of seizures, epilepsy syndrome, magnetic resonance imaging (MRI) abnormalities, epilepsy surgery, and withdrawal outcomes of patients with epilepsy. Many factors are associated with recurrent seizures after AED withdrawal. For patients who are seizure-free after treatment, the role of an electroencephalogram (EEG) alone in ensuring safe withdrawal is limited. A series of prediction models for the postwithdrawal recurrence risk have incorporated various potentially important factors in a comprehensive analysis. We focused on the populations of studies investigating five risk prediction models and analyzed the predictive variables and recommended applications of each model, aiming to provide a reference for personalized withdrawal for patients with epilepsy in clinical practice.
[ARTICLE] Basic and clinical role of vitamins in epilepsy – Full Text PDF
Posted by Kostas Pantremenos in Epilepsy on February 28, 2020
Abstract
Background & Aims: Epilepsy is a brain disorder which affects about 50 million people worldwide. Good diet is an essential measure to controlling seizure attacks. Since some combination therapy can reduce epileptogenesis, therefore this review summarizes the available evidences about the application of vitamins in animal models and humans for understanding what specific combinations of antiepileptic drugs and vitamins are likely to be effective for epilepsy therapy.
Material and methods: In this review, electronic databases including PubMed and Google Scholar were searched for monotherapy and polytherapy by vitamins.
Results: Administration of vit A inhibits development of seizures and lethality in animal models. Also vitamins B1, B6 and B12 pretreatment might lead to a protective effect against degenerative cellular in mice. In addition use of low dose of sodium valproate with vitamins C or E increase the anticonvulsant activity of the drug in mice. Moreover, Vitamin D enhances antiepileptic effects of lamotrigine, phenytoin and valproate in animal’s models. Vitamin E has an anticonvulsant effect in ferrous chloride seizures, hyperbaric oxygen seizures as well as penicillin-induced seizures in contrast kindling, maximal electroshock and kainite models. Some researches demonstrated that vitamins D and B as adjunctive therapy in epileptic patient can relieve seizures. A clinical data have shown beneficial effects of vitamin E in raising total antioxidant capacity, catalase, and glutathione in patients with uncontrolled epilepsy. Only few clinical studies exist to support the efficacy of the vitamin A and K in epilepsy.
Conclusion: However vitamin therapy is not a substitute for antiepileptic drugs but add on therapy by them may relieve drugs-induced deficiencies as well as more researches are needed to evaluate the effectiveness of vitamins in epileptic humans.
[…]
[Abstract + References] Therapeutic Drug Monitoring of Antiepileptic Drugs in Women with Epilepsy Before, During, and After Pregnancy – Review
Posted by Kostas Pantremenos in Epilepsy, Pharmacological on January 11, 2020
Abstract
During pregnancy, the pharmacokinetics of an antiepileptic drug is altered because of changes in the clearance capacity and volume of distribution. These changes may have consequences for the frequency of seizures during pregnancy and fetal exposure to antiepileptic drugs. In 2009, a review was published providing guidance for the dosing and therapeutic drug monitoring of antiepileptic drugs during pregnancy. Since that review, new drugs have been licensed and new information about existing drugs has been published. With this review, we aim to provide an updated narrative overview of changes in the pharmacokinetics of antiepileptic drugs in women during pregnancy. In addition, we aim to formulate advice for dose modification and therapeutic drug monitoring of antiepileptic drugs. We searched PubMed and the available literature on the pharmacokinetic changes of antiepileptic drugs and seizure frequency during pregnancy published between January 2007 and September 2018. During pregnancy, an increase in clearance and a decrease in the concentrations of lamotrigine, levetiracetam, oxcarbazepine’s active metabolite licarbazepine, topiramate, and zonisamide were observed. Carbamazepine clearance remains unchanged during pregnancy. There is inadequate or no evidence for changes in the clearance or concentrations of clobazam and its active metabolite N-desmethylclobazam, gabapentin, lacosamide, perampanel, and valproate. Postpartum elimination rates of lamotrigine, levetiracetam, and licarbazepine resumed to pre-pregnancy values within the first few weeks after pregnancy. We advise monitoring of antiepileptic drug trough concentrations twice before pregnancy. This is the reference concentration. We also advise to consider dose adjustments guided by therapeutic drug monitoring during pregnancy if the antiepileptic drug concentration decreases 15–25% from the pre-pregnancy reference concentration, in the presence of risk factors for convulsions. If the antiepileptic drug concentration changes more than 25% compared with the reference concentration, dose adjustment is advised. Monitoring of levetiracetam, licarbazepine, lamotrigine, and topiramate is recommended during and after pregnancy. Monitoring of clobazam, N-desmethylclobazam, gabapentin, lacosamide, perampanel, and zonisamide during and after pregnancy should be considered. Because of the risk of teratogenic effects, valproate should be avoided during pregnancy. If that is impossible, monitoring of both total and unbound valproate is recommended. More research is needed on the large number of unclear pregnancy-related effects on the pharmacokinetics of antiepileptic drugs.
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[Abstract] Pharmacology and epilepsy : update on the new antiepileptic drugs
Posted by Kostas Pantremenos in Epilepsy, Pharmacological on May 3, 2019
Abstract
New antiepileptic drugs are regularly approved for treatment and offer large therapeutic opportunities. Efficacy of these drugs is relatively similar on-label with different mechanisms to be combined for a synergic effect. Treatments such as cannabidiol have benefitted from large media coverage despite limited clinical evidence so far. The objective of antiepileptic drugs is to stop the recurrence of epileptic seizures with as few adverse events as possible. When confronted to a difficult-to-treat epilepsy, referral to a specialised centre is strongly advised. The aim is to confirm that the diagnosis is correct, that the treatment is well adapted (indication, pharmacokinetic and compliance) and to evaluate the indication for non-pharmacological treatments such as epilepsy surgery.
via [Pharmacology and epilepsy : update on the new antiepileptic drugs]. – Abstract – Europe PMC
[Abstract] Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy – A retrospective single center study
Posted by Kostas Pantremenos in Epilepsy, Uncategorized on November 25, 2018
Highlights
- •
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Pregnancies in women with epilepsy (WWE) increased significantly during our 11-year study period (41% increase).
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Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015) with Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%) most commonly used.
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Valproic acid use was markedly reduced comparing the years 2005-2010 (18.4%) and 2011-2015 (9.4%), a reduction of 48%.
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Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.
Abstract
Purpose
Antiepileptic drugs (AED) are among the most common teratogenic drugs prescribed to women of childbearing age. During pregnancy, the risk of seizures has to be weight against the use of AED treatment. Primary goal was to observe and describe AED treatment policy and its changes during an eleven-year period at our third referral center.
Methods
We scrutinized the medical health records for all cases of female epileptic patients admitted for labor at the Rabin Medical Center during the years 2005 – 2015.
Results
A total of 296 deliveries were recorded with 136 labors occurring in the period 2005-2010 (22.7/y) and 160 in 2011-2015 (32.0/y; increase of 41%). Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015). Most commonly used AEDs during pregnancy were Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%). Comparing their use during the years 2005-2010 and 2011-2015, Lamotrigine (35.3% vs. 36.9%) and Carbamazepine use (23.5% vs. 26.0%) increased slightly. Valproic acid use was markedly reduced in the second period: 18.4% in the years 2005-2010 lowered to 9.4% during 2011-2015, a reduction of 48%. Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.
Conclusions
The proportion of WWE treated with VPA during pregnancy was significantly reduced in the observed period (2005-2015). Change in fetal outcome during this period for WWE could not be detected.
[REVIEW] Summary of Antiepileptic Drugs Available in the United States of America – AMERICAN EPILEPSY SOCIETY
Posted by Kostas Pantremenos in Epilepsy on September 6, 2018
The current review summarizes the
main antiepileptic drugs available for
prescription in the United States as of
July 2018. One condensed, and one
expanded, table of the major properties
of 28 AEDs are presented both
to assist clinicians in providing care to
persons with epilepsy and to facilitate
the training of those in health care
educational programs.
This table is not intended to constitute
recommendations, only to provide an
easy reference listing of products on
the market.
[Abstract] Affective and behavioral dysfunction under antiepileptic drugs in epilepsy: Development of a new drug-sensitive screening tool
Posted by Kostas Pantremenos in Epilepsy on July 30, 2018
Highlights
Abstract
Objective
Behavioral problems and psychiatric symptoms are common in patients with epilepsy and have a multifactorial origin, including adverse effects of antiepileptic drugs (AEDs). In order to develop a screening tool for behavioral AED effects, the aim of this study was to identify behavioral problems and symptoms particularly sensitive to AED drug load and the presence/absence of AEDs with known negative psychotropic profiles.
Methods
Four hundred ninety-four patients with epilepsy were evaluated who had been assessed with three self-report questionnaires on mood, personality, and behavior (Beck Depression Inventory, BDI; Neurological Disorders Depression Inventory for Epilepsy extended, NDDI-E; and Fragebogen zur Persönlichkeit bei zerebralen Erkrankungen, FPZ). Drug-sensitive items were determined via correlation analyses and entered into an exploratory factor analysis for scale construction. The resulting scales were then analyzed as a function of drug treatment.
Results
Analyses revealed 30 items, which could be allocated to six behavioral domains: Emotional Lability, Depression, Aggression/Irritability, Psychosis & Suicidality, Risk- & Sensation-seeking, and Somatization. Subsequent analysis showed significant effects of the number of AEDs on behavior, as in Emotional Lability (F = 2.54, p = .029), Aggression/Irritability (F = 2.29, p = .046), Psychosis & Suicidality (F = 2.98, p = .012), and Somatization (F = 2.39, p = .038). Affective and behavioral difficulties were more prominent in those patients taking AEDs with supposedly negative psychotropic profiles. These effects were largely domain-unspecific and primarily manifested in polytherapy.
Conclusion
Drug-sensitive behavioral domains and items were identified which qualify for a self-report screening tool. The tool indicates impairments with a higher drug load and when administering AEDs with negative psychotropic profiles. The next steps require normalization in healthy subjects and the clinical validation of the newly developed screening tool PsyTrack along with antiepileptic drug treatment.
TBI Rehabilitation 