Antiepileptic Drugs Of Choice Research Articles

Epilepsy in the aged : Challenges in diagnostics and treatment

Epilepsien stellen nach Demenzen und Schlaganfall die dritthäufigste neurologische Krankheitsgruppe bei älteren Menschen dar. Die Inzidenz der Epilepsien steigt im Alter, sodass aufgrund demografischer Entwicklungen in den kommenden Jahren mit einer weiteren Zunahme älterer Patienten mit Epilepsie zu rechnen ist. Die häufigsten Ursachen der Altersepilepsie stellen zerebrovaskuläre Erkrankungen und Demenzen dar. Anfälle bei älteren Menschen werden oft spät erkannt. Das Auftreten eines Status epilepticus ist bei älteren Patienten häufiger und mit erhöhter Morbidität und Letalität vergesellschaftet. Die medikamentöse Behandlung älterer Patienten wird durch Komorbiditäten und Polypharmazie erschwert, wobei Antiepileptika mit geringem Interaktionsprofil und guter Verträglichkeit zur Behandlung der Altersepilepsie gewählt werden sollten. Levetiracetam und Lamotrigin sind aufgrund geringer Interaktionen und guter Verträglichkeit Antiepileptika erster Wahl beim älteren Patienten.

Effect of Newer Generation Anticonvulsant Prophylaxis on Seizure Incidence After Spontaneous Intracerebral Hemorrhage

The role of prophylactic antiepileptic drugs (AEDs) in preventing seizures and/or improving the outcomes after intracerebral hemorrhage (ICH) has remained controversial. The current guidelines have recommended against AED prophylaxis. However, these recommendations were based on older studies that had primarily used phenytoin as the AED of choice. Newer medications, such as levetiracetam, have yet to be extensively studied. We performed a retrospective review of patients with ICH from 2010 to 2015. The patient demographic data, seizure data, and outcomes were collected. The results were analyzed using descriptive statistics, binary logistic regression, and quantile regression. The primary outcome was seizure incidence. A total of 360 patients with a median age of 70 years had met the inclusion criteria. Of the 360 patients, 30 (8.3%) had had recorded seizure events, 54% were men, and 81% had a history of hypertension. The median admission National Institutes of Health stroke scale (NIHSS) score was 7 (interquartile range [IQR], 14), and the median discharge NIHSS score was 5.0 (IQR, 13). The median hematoma size was 7.1 mL (IQR, 13 mL), and 143 patients (40%) had had cortical involvement. Of the 360 patients, 273 (76%) had received prophylaxis and 87 (24%) had not. After adjustment for the admission NIHSS and the presence of cortical involvement, the rate of new seizure events after ICH remained significantly lower for the patients who had received AED prophylaxis (adjusted odds ratio, 0.28; 95% confidence interval, 0.11-0.71; P= 0.008). The administration of, predominantly, levetiracetam for AED prophylaxis after ICH reduced the odds of new seizure events, independently of the admission NIHSS score and the presence of cortical involvement.

Seizure associated with clozapine: incidence, etiology, and management.

Seizures are a known adverse effect of clozapine therapy. The literature varies on incidence rates of seizures, secondary to varying time frames in which each seizure occurred. Tonic-clonic seizures comprise the majority of seizures experienced secondary to clozapine use, but it is imperative to recognize the potential variety of seizure presentation. The exact etiology of clozapine-induced seizure is unknown. Conflicting reports regarding total oral dose, serum concentration, dose titration, and concomitant medications make it difficult to identify a single cause contributing to seizure risk. Following seizure occurrence, it may be in the best interests of the patient to continue clozapine treatment. In this clinical situation, the use of an antiepileptic drug (AED) for seizure prophylaxis may be required. The AED of choice appears to be valproate, but several successful case reports also support the use of lamotrigine, gabapentin and topiramate. Well-designed clinical trials regarding clozapine seizure prophylaxis are lacking. Given clozapine's strong evidence for efficacy in the treatment of schizophrenia and schizoaffective disorder, every attempt to manage side effects, including seizure, should be implemented to allow for therapeutic continuation.

Safe Treatment of Seizures in the Setting of HIV/AIDS

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

Valproic acid as the AED of choice for patients with glioblastoma?

Seizures occur in approximately 30%–50% of patients with glioblastomas. Patients with glioblastomas who do not have seizures generally should not receive prophylactic antiepileptic drugs (AEDs).1 For patients with seizures associated with their tumor, standard AEDs are used, although the optimal agents are unknown. A retrospective analysis of 3 North Central Cancer Treatment Group (NCCTG) trials suggested that newly diagnosed patients with GBM receiving cytochrome P450 enzyme-inducing AED (EIAED) may have a better outcome.2 However, another review did not confirm this benefit.3 At present, the majority of brain tumor patients requiring AEDs are treated with non-EIAEDs such as levetiracetam. These non-EIAEDs do not affect the metabolism of commonly administered antitumor agents and corticosteroids, and usually have little impact on blood counts, an important factor since most glioblastoma patients receive chemotherapy. Currently, standard postsurgical therapy for patients with newly diagnosed glioblastoma is radiation therapy with concomitant temozolomide, followed by 6 months of adjuvant temozolomide, based on a study conducted by the European Organization for Research and Treatment of Cancer and the National Cancer Institute of Canada.4 In this issue of Neurology ®, Weller et al.5 retrospectively analyzed the use of AEDs in patients enrolled in that trial and correlated the results with survival, adjusting for known …

The relationship between sleep and epilepsy: the effect on cognitive functioning in children

The purpose of this review was to examine the possible pathophysiological links between epilepsy, cognition, sleep macro- and microstructure, and sleep disorders to highlight the contributions and interactions of sleep and epilepsy on cognitive functioning in children with epilepsy. PubMed was used as the medical database source. No language restriction was placed on the literature searches, and citations of relevant studies in the paediatric age range (0-18 y) were checked. Studies including a mixed population but with a high percentage of children were also considered. The searches identified 223 studies. One reviewer scanned these to eliminate obviously irrelevant studies. Three reviewers scanned the remaining 128 studies and their relevant citations. The review showed that several factors could account for the learning impairment in children with epilepsy: aetiology, electroencephalographic (EEG) discharges, and persistence and circadian distribution of seizures, etc. EEG discharges may affect cognition and sleep, even in the absence of clinical or subclinical seizures. The sleep deprivation and/or sleep disruption affect the neurophysiological and neurochemical mechanisms important for the memory-learning process, but also influence the expression of EEG discharges and seizures. Learning and memory consolidation can take place over extended periods, and sleep has been demonstrated to play a fundamental role in these processes through neuroplastic remodelling of neural networks. Epilepsy and EEG paroxysms may affect sleep structure, interfering with these physiological functions. Improvement in the long-term cognitive-behavioural prognosis of children with epilepsy requires both good sleep quality and good seizure control. The antiepileptic drug of choice should be the one that interferes least with sleep structure and has the best effect on sleep architecture--thus normalizing sleep instability, especially during non-rapid eye movement sleep.

Joint modelling of longitudinal and competing risks data

Available methods for joint modelling of longitudinal and survival data typically have only one failure type for the time to event outcome. We extend the methodology to allow for competing risks data. We fit a cause-specific hazards sub-model to allow for competing risks, with a separate latent association between longitudinal measurements and each cause of failure.The method is applied to data from the SANAD trial of anti-epileptic drugs (AEDs), as a means of investigating the effect of drug titration on the relative effects of lamotrigine (LTG) and carbamazepine (CBZ) on treatment failure. Concern had been expressed that differential titration rates may have been to the disadvantage of CBZ. The beneficial effect of LTG on unacceptable adverse events leading to drug withdrawal did not lessen and indeed increased slightly when a calibrated dose was accounted for in the joint model. Adjustment for the titration rate of LTG relative to CBZ resulted in an unchanged effect of the former on drug withdrawals due to inadequate seizure control. LTG remains the AED of choice from this analysis.

Antiepileptic drug therapy

Successful treatment of seizure disorders in small animals requires proper patient assessment, understanding the principles of antiepileptic drug (AED) therapy, designing a strategy for pharmacotherapy, and plans for emergency treatment. Several levels of assessment are needed in managing an epileptic patient to include the diagnosis, effectiveness of therapy, and health-related quality of life assessments. Three levels of diagnosis are important in determining the appropriate AED therapy: 1) confirmation that an epileptic seizure has occurred, and if so, the seizure type(s) manifested; 2) diagnosis of the seizure etiology; and 3) determination of an epileptic syndrome. Monotherapy is the initial goal of treating any cat or dog with epilepsy to reduce possible drug-drug interactions and adverse effects. Unfortunately, many of the AEDs useful in people cannot be prescribed to small animals either due to inappropriate pharmacokinetics (too rapid of an elimination), and potential hepatotoxicity. Thus, the most commonly used AEDs in veterinary medicine are from the same mechanistic category, that of enhancing inhibition of the brain. Antiepileptic drugs can be classified into three broad mechanistic categories: 1) enhancement of inhibitory processes via facilitated action of gamma amino-butyric acid (GABA); 2) reduction of excitatory transmission; and 3) modulation of membrane cation conductance. Pharmacotherapy strategies should be designed based on the decision when to start treatment, choice of the appropriate AED, and proper AED monitoring and adjustment. Information is presented for the current AEDs of choice, phenobarbital and bromide. Additional guidelines are provided for administration of newer AEDs, felbamate and gabapentin. All owners should be aware that emergency therapy may be necessary if recurrent or severe seizures occur in their pet. A rapid, reliable protocol is presented for the emergency management of seizuring cats and dogs in the hospital and at home. Home treatment with per rectal administration of diazepam in the dog has proven to be an effective means of reducing seizure frequency and owner anxiety. Treating each animal as an individual, applying the philosophy that seizure prevention is better than intervention, and consulting specialists to help formulate or revise treatment plans will lead to improved success in treating seizure disorders in the cat and dog.

Altered Cognitive Functioning in Children With Idiopathic Epilepsy Receiving Valproate Monotherapy

Once a child is diagnosed with epilepsy, a primary concern is whether or not the child's behavior and cognitive abilities will be affected by the disease, by the drug prescribed for seizure control, or both. Direct cognitive effects by the epileptic condition have been described. On the other hand, cognitive effects in epilepsy have been attributed to antiepileptic drug therapy. Valproate is an antiepileptic drug of choice in managing the commonest childhood epilepsy syndromes. Although frequently prescribed in pediatric neurology practice, there have been relatively few studies investigating the cognitive effects of valproate therapy in children. Cognitive effects of valproate reported in normal adult volunteers and in adults with epilepsy cannot be generalized to the pediatric population. The results of investigations on children are less conclusive. Guidelines for antiepileptic drug trials in children have recently been formulated. Carefully designed studies are required in determining the cognitive effects of valproate in the pediatric population. Neuropsychological measures that are likely to assess subtle changes in higher brain functions crucial to learning in children should be employed. We propose a test battery to assess for cognitive changes associated with anticonvulsant therapy in children.

Efficacy and adverse effects of established and new antiepileptic drugs.

Antiepileptic drug (AED) selection is based primarily on efficacy for specific seizure types and epileptic syndromes. However, efficacy is often similar for the different AEDs, and other properties such as adverse effects, pharmacokinetic properties, and cost may also be of importance. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the AED of choice is valproate (VPA). Secondarily generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single AED or combination of AEDs. The AEDs of choice for absence seizures are ethosuximide (ESM) and VPA. For control of primary generalized tonic-clonic seizures, any of the other major AEDs can be effective. If VPA cannot be prescribed, carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), or primidone (PRM) may be effective, but ESM or a benzodiazepine (BZD) must be added to control associated absence or myoclonic seizures. The AEDs of first choice for partial epilepsies with partial and secondarily generalized tonic-clonic seizures are CBZ and PHT. Increasing evidence suggests that VPA is a good alternative when CBZ and PHT fail. PB and PRM are second-choice selections because of adverse effects. A combination of two of the five standard AEDs may be necessary to treat intractable seizures, but no studies have been done to indicate an optimal combination. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, alcoholic epilepsy, and status epilepticus require specific AED treatment. Ultimately, AED selection must be individualized. No "drug of choice" can be named for all patients. The expected efficacy for the seizure type, the importance of the expected adverse effects, the pharmacokinetics, and the cost of the AEDs all must be weighed and discussed with the patient before a choice is made. A number of new AEDs with unique mechanisms of action, pharmacokinetic properties, and fewer adverse effects hold important promise of improved epilepsy treatment.

Antiepileptic drugs in pediatric practice.

Several factors characterize the current medical treatment of epilepsy during childhood. Children do not present the same types of seizures or epilepsies as adults, and certain epilepsy syndromes are seen only during childhood. Accordingly, the choice of antiepileptic drugs (AEDs) may differ in children. In addition, certain medical therapies, such as ACTH or pyridoxine, are used only in children. It is also common practice to prescribe AEDs in children for indications that are "off-label," such as the treatment of partial-onset seizures with carbamazepine before the age of 6 years. The natural history of epilepsy and the risk for seizure recurrence may be different in the pediatric age range, and this may influence the decision to institute chronic prophylactic therapy in children. Similar considerations may apply to the decision to discontinue AED therapy. The pharmacokinetics of several AEDs are age-dependent, and dosages are more variable among patients. The adverse effects of AEDs may be age-dependent, and the pattern of exacerbation of certain seizures by AEDs may be different in children. In addition, several new AEDs are now available, or are about to be released, and the preferential sequence of AEDs of choice in children with epilepsy will need to be reassessed as experience grows and as the results of comparative studies become available.

Complex Partial Seizures: Clinical Features and Differential Diagnosis

Complex partial seizures are the most common seizure type in patients with partial epilepsy. Most complex partial seizures emanate from the temporal lobe; however, the seizures also may be extratemporal in origin. The clinical phenomenology may distinguish complex partial seizures from nonepileptic paroxysmal disorders and other seizure types. Physiologic and psychological disorders need to be considered in the differential diagnosis of seizure activity. Long-term EEG monitoring may be necessary for select patients to confirm the diagnosis of epilepsy and to classify appropriately seizure type. Carbamazepine and phenytoin are the antiepileptic drugs of choice in the management of complex partial seizures. Polypharmacy and use of cognitively impairing antiepileptic drugs may reduce patient compliance and further impair the quality of life of the patient with epilepsy. Finally, epilepsy surgery is an important alternative for the patient with intractable partial seizures.