Выбор АЭПов при идеопатической ГСП эпилепсии.

[Бедолага]

Idiopathic generalized epilepsy and choice of antiepileptic drugs
Selim R. Benbadis, MD, William O. Tatum, IV, DO and Maria Gieron, MD
From the Comprehensive Epilepsy Program, Departments of Neurology (Drs. Benbadis, Tatum, and Gieron), Neurosurgery (Dr. Benbadis), and Pediatrics (Dr. Gieron), University of South Florida and Tampa General Hospital, Tampa, FL.

Кратенько:

The exact mechanism of action of AED remains unclear, and there is no obvious reason why some AED should not work well in IGE. Nonetheless, there is abundant evidence that some AED are not optimal choices for IGE (see table 1). These "non-broad-spectrum" AED include sodium channel blockers (PHT, CBZ, OXC) and GABAergic molecules (GBP, TGB, vigabatrin–not available in the USA). Our most important finding is that the majority (70%) of patients with IGE were receiving ill-advised AED, mostly PHT or CBZ. As expected, most patients were doing poorly until they were switched to an appropriate AED. Twenty-five of 32 patients (78%) who were switched became fully controlled, as would be expected for IGE.1–4

A similar problem has been reported for JME, in which one-quarter of patients are receiving ill-advised AED at the time of diagnosis,5 but the same issue applies to IGE at large. Our proportion was even higher, which is understandable because most of our patients had a form of IGE not as well defined as JME. As has been reported (see table 2), we also found that inappropriate AED can worsen IGE to the point of status. The drug of choice for IGE is classically VPA. Among the newer AED, there is increasing evidence that LEV, LTG, TPM, and ZNS are most likely broad spectrum and effective in IGE (table 3), and this is also the opinion of an expert consensus panel.6 The use of these newer AED is "off-label," and it is possible that they are not used in IGE because they are not specifically approved for this indication. However, none of the AED has any official indication for IGE. In fact, AED generally have indications for seizure types rather than syndromes, which may be unfortunate.7 The International League Against Epilepsy explicitly recommends that the classification of syndromes be "used daily in communication between colleagues" and be the "subject of clinical trials and other investigations."7 Yet the official labeling of AED does not mention any epilepsy syndromes, much less specific types such as IGE.

Our findings have important clinical implications. First, they confirm the view that a poor choice of AED is probably the main cause of IGE that are seemingly refractory to treatment4 and that the inappropriateness of some AED for IGE is either not well known or neglected. Second, it highlights the importance of diagnosing the type of epilepsy or syndrome.7 Although arriving at a specific syndrome is not always possible, at least a broad categorization into localization-related, symptomatic generalized epilepsy or IGE is usually possible,7 in fact even after a first seizure.8 A related issue is the widespread assumption that IGE are rare beyond childhood2 and thus of little concern to adult neurologists. As a result, GTC seizures (especially in adults) may be assumed to be secondarily generalized, that is, focal epilepsy.2 This tendency to overdiagnose focal epilepsies can have serious consequences beyond the choice of medications.9 In fact, a significant proportion of IGE begin beyond childhood and adolescence: 35% after age 1810 and 28% after age 20.2 Similarly, in a study of 300 patients with new-onset seizures (at a mean age of 25), one-quarter turned out to have an IGE.8 Thus, whereas differentiating among the specific syndromes of IGE is of relatively minor importance, making a diagnosis of IGE as a group (as opposed to localization-related epilepsy or a symptomatic/cryptogenic generalized epilepsy) has critical implications for patient care.

Полная статья:

http://rapidshare.com/files/89812567/1793.pdf

Вообще, говорите, что выложить...

[Бедолага]

Brain 2006 129(5):1281-1292; doi:10.1093/brain/awl047

Absence and myoclonic status epilepticus precipitated by antiepileptic drugs in idiopathic generalized epilepsy Pierre Thomas1, Luc Valton2 and Pierre Genton3

Краткое содержание:

Aggravation of idiopathic generalized epilepsy (IGE) syndromes by inappropriate antiepileptic drugs (AEDs) is increasingly recognized as a serious and common problem. Precipitation of status epilepticus (SE) by inappropriate medication has rarely been reported. We retrospectively studied all adult patients with IGE taking at least one potentially aggravating AED, who developed video-EEG documented SE over 8 years, and whose long-term outcome was favourable after adjustment of medication. We identified 14 patients (seven male patients) aged 15–46 years with a mean duration of epilepsy of 16.4 years. Video-EEG demonstrated typical absence SE (ASE) in five, atypical ASE in five, atypical myoclonic SE (MSE) in three and typical MSE in one. Epilepsy had been misclassified as cryptogenic partial in eight cases and cryptogenic generalized in four. The correct diagnosis proved to be juvenile absence epilepsy (JAE) in six patients, juvenile myoclonic epilepsy (JME) in four, epilepsy with grand mal on awakening (EGMA) in two and childhood absence epilepsy (CAE) in two. All patients had been treated with carbamazepine (CBZ) and had experienced seizure aggravation or new seizure types before referral. Seven patients had polytherapy with phenytoin (PHT), vigabatrin (VGB) or gabapentin (GBP). Potential precipitating factors included dose increase of CBZ or of CBZ and PHT; initiation of CBZ, VGB or GBP; and decrease of phenobarbital. Withdrawal of the aggravating agents and adjustment of medication resulted in full seizure control. This series shows that severe pharmacodynamic aggravation of seizures in IGE may result in ASE or MSE, often with atypical features

Есть желание -выложу полностью.

[Бедолага]

NEUROLOGY 2005;65:1737-1743


Double-blind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures

V. Biton, MD, J. C. Sackellares, MD, A. Vuong, A. E. Hammer, P. S. Barrett, PharmD and J. A. Messenheimer, MD
From Arkansas Epilepsy Program (Dr. Biton), Little Rock; University of Florida and Malcolm Randall VA Medical Center (Dr. Sackellares), Gainesville; and GlaxoSmithKline (A. Vuong, A.E. Hammer, and Drs. Barrett and Messenheimer), Research Triangle Park, NC.

Address correspondence and reprint requests to Dr. Victor Biton, Arkansas Epilepsy Program, Two Lile Court, Suite 100, Little Rock, AR 72205; e-mail: vbiton@alltel.net

Objective: To evaluate the efficacy and tolerability of adjunctive lamotrigine in primary generalized tonic-clonic (PGTC) seizures in a randomized, double-blind, placebo-controlled trial.

Methods: Patients with a diagnosis of epilepsy with PGTC seizures who were receiving one or two antiepileptic drugs at study entry were eligible. Patients with partial seizures were excluded on the basis of seizure history and screening EEGs. The study comprised a baseline phase, an escalation phase during which study medication was titrated to a target dose, and a 12-week maintenance phase during which doses of lamotrigine/placebo and concomitant antiepileptic drugs were maintained.

Results: Of the 121 randomized patients ages 2 to 55 years, 117 (58 lamotrigine, 59 placebo) entered the escalation phase and received study medication. During the escalation and maintenance phases combined, median percent reduction in PGTC seizure frequency was 66.5% with lamotrigine compared with 34.2% with placebo (p = 0.006). The corresponding numbers for lamotrigine and placebo were 60.6% and 32.8% (p = 0.038) during the escalation phase and 81.9% and 43.0% (p = 0.006) during the maintenance phase. During the maintenance phase, 72% of lamotrigine-treated patients compared with 49% of placebo-treated patients experienced a 50% reduction in frequency of PGTC seizures (p = 0.014). A similar pattern of results was observed for all generalized seizures. The most common drug-related adverse events were dizziness (5% lamotrigine, 2% placebo), somnolence (5% lamotrigine, 2% placebo), and nausea (5% lamotrigine, 3% placebo).

Conclusions: Adjunctive lamotrigine is effective in the treatment of primary generalized tonic-clonic seizures and has a favorable tolerability profile.

[Василий Генералов]

Тема актуальна, спасибо,
жаль, что я отвечаю с разных IP и руки не доходят со своего компа набрасать обзоров и гидлайнов... Обещаю наверстать, как нибудь на выходных. Поэтому то что пишу - это из головы, без точных ссылок. Но ссылки есть....

[Бедолага]

Тема актуальна, спасибо,
жаль, что я отвечаю с разных IP и руки не доходят со своего компа набрасать обзоров и гидлайнов... Обещаю наверстать, как нибудь на выходных. Поэтому то что пишу - это из головы, без точных ссылок. Но ссылки есть....

ОК!
Ну я накидаю пока, что успел найти.

Вот статейка из NEUROLOGY 2005;65:1737-1743

Double-blind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures V. Biton, MD, J. C. Sackellares, MD, A. Vuong, A. E. Hammer, P. S. Barrett, PharmD and J. A. Messenheimer, MD

Та мдаже есть схемка под названием

Algorithm for using EEG to exclude patients with partial seizures from the study. PGTC = primary generalized tonic-clonic seizures.





Few data from well-controlled clinical trials are available to differentiate among anticonvulsant medications for PGTC seizures. Factors that limit the ability to draw conclusions about results of many studies of PGTC seizures include the virtual absence of placebo-controlled studies requiring a prospective EEG to confirm diagnosis and the failure to differentiate PGTC seizures from partial seizures with secondary generalization systematically. In the current study, these shortcomings were addressed by including a placebo control group and by excluding patients with partial seizures on the basis of seizure history and EEG. The results show that adjunctive lamotrigine is more effective than placebo at controlling PGTC seizures and all generalized seizures. Although the placebo response rate is higher than might be expected in a study of partial seizures, it is similar to the placebo response seen in previous controlled trials of PGTC seizures.10,11

The reduction in seizure types in addition to PGTC seizures with lamotrigine compared with placebo during the maintenance phase is important in establishing, with evidence from other lamotrigine clinical trials, the spectrum of activity of lamotrigine in the treatment of epileptic seizures in adults and children. This study was not designed to assess effects of lamotrigine on other seizure types (absence, myoclonic seizures) often associated with PGTC seizures. However, there was no evidence that lamotrigine was associated with deterioration of control of other seizures. No patient in the lamotrigine group prematurely withdrew from the study because of increased frequency of myoclonic seizures.

This study, as a double-blind, placebo-controlled evaluation of an anticonvulsant for PGTC seizures, extends previous research.10,12 A placebo-controlled study of topiramate that excluded patients thought to have partial seizures has been reported.10 Another published placebo-controlled trial of generalized tonic-clonic seizures—a negative trial of gabapentin—did not exclude patients with partial seizures.12

Lamotrigine exhibited a favorable tolerability profile as adjunctive therapy in this study. The most common adverse events that investigators considered to be possibly, probably, or definitely related to study medication were dizziness, somnolence, and nausea. Although one lamotrigine-treated patient with a nonserious rash was prematurely withdrawn from the study as required by the protocol, no serious rashes were reported in these patients as young as 2 years.

The current study corroborates other findings establishing the efficacy and tolerability of lamotrigine for a range of generalized seizure types.1,2,13–22 In addition to being demonstrated effective for PGTC seizures, lamotrigine is indicated in adults and children 2 years and older as adjunctive therapy for partial seizures with or without secondary generalization, as adjunctive therapy for generalized seizures of the Lennox-Gastaut syndrome, and, in the United States, for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing antiepileptic drug or valproate. The efficacy profile of lamotrigine makes it an appropriate therapeutic option when it is not possible to determine conclusively whether a patient having GTC seizures has idiopathic generalized epilepsy or focal epilepsy.

Ща ссылку дам полную...

О!

http://rapidshare.com/files/89818661/1737.pdf

[Бедолага]

Modern antiepileptic drugs: guidelines and beyond

Curr Opin Neurol 19:175–180.
2006 Lippincott Williams & Wilkins.

Purpose of review
Ten antiepileptic drugs have been licensed since 1990.
Their usage will be briefly reviewed focusing on new data
and inclusion in guidelines. The hypotheses exploring the
underlying basis of pharmacoresistance will be presented.
Recent findings
Lamotrigine, gabapentin, topiramate, and oxcarbazepine
are available for use as monotherapy in many countries
following comparative studies with older antiepileptic
drugs. Zonisamide and pregabalin have recently obtained
licences as adjuvant therapy in the US and Europe for partial
epilepsy with or without secondary generalization. The UK
National Institute for Clinical Excellence guideline has
advised, largely based on cost, against the routine use of
modern antiepileptic drugs, except when older drugs have
failed or are contraindicated. This contrasts with the US
guidelines which are less conservative. Surgically resected
specimens from patients with refractory epilepsy have led to
the development of two hypotheses to explain
pharmacoresistant epilepsy.
Summary
The introduction of 10 new antiepileptic drugs has provided
greater choice for patients and doctors, although evidence
in support of their superiority over the older drugs is sparse.
This has led to conflicting advice in guidelines. Recent
developments in the understanding of pharmacoresistance
may explain the relatively high incidence of refractory
epilepsy.

Полный текст:

http://rapidshare.com/files/101894427/Modern_AEDs.pdf