- •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
[ARTICLE] Medication use in poststroke epilepsy: A descriptive study on switching of antiepileptic drug treatment – Full Text
- 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.
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.
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.
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.
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.
Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly . 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 , 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 . 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.[…]
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.
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.
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.
[ARTICLE] Prediction of the Recurrence Risk in Patients With Epilepsy After the Withdrawal of Antiepileptic Drugs – Full Text PDF
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.
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
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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Patsalos PN, Gougoulaki M, Sander JW. Perampanel serum concentrations in adults with epilepsy: effect of dose, age, sex and concomitant anti-epileptic drugs. Ther Drug Monit. 2016;38:358–64.
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[Abstract] Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy – A retrospective single center study
Pregnancies in women with epilepsy (WWE) increased significantly during our 11-year study period (41% increase).
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.
Valproic acid use was markedly reduced comparing the years 2005-2010 (18.4%) and 2011-2015 (9.4%), a reduction of 48%.
Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.
[REVIEW] Summary of Antiepileptic Drugs Available in the United States of America – AMERICAN EPILEPSY SOCIETY
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
This table is not intended to constitute
recommendations, only to provide an
easy reference listing of products on
[Abstract] Affective and behavioral dysfunction under antiepileptic drugs in epilepsy: Development of a new drug-sensitive screening tool
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.
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.
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.
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.
Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, e.g., pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug’s prescribing indications, key pharmacokinetic characteristics, associated drug-drug pharmacokinetic interactions and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total vs free concentrations in blood vs saliva) and sample collection and processing.
The present review is based on published articles and searches in PubMed and Google Scholar, last searched March in 2018, in addition to references from relevant papers.
In total, 171 relevant references were identified and used to prepare this review.
TDM provides a pragmatic approach to epilepsy care in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone and valproic acid), much data has accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin and zonisamide).