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      Adjunctive therapy for the treatment of primary generalized tonic-clonic seizures: focus on oncedaily lamotrigine


      Drug Design, Development and Therapy

      Dove Medical Press

      lamotrigine, GTC, IGE, generalized seizures, treatment

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          Idiopathic generalized epilepsies are frequently encountered by neurologists, and providing an accurate diagnosis and effective treatment(s) are the necessary components of successful patient care. With the introduction of new antiepileptic medications, physicians are better equipped for this goal. The immediate-release formulation of lamotrigine (LTG-IR) has been approved for primary generalized tonic-clonic seizures since 2006. The extended-release formulation of lamotrigine (LTG-XR) was approved for adjunctive therapy in patients with primary generalized tonic-clonic seizures in 2010. Although its exact mechanism of action is not yet fully elucidated, studies have demonstrated multiple possible pathways. Although both the LTG-IR and LTG-XR formulations have similar side effects and are generally well tolerated, LTG-XR may be preferable for its ease of use, which may increase patient compliance and decrease fluctuations in serum drug levels. The ease of conversion between the formulations also makes lamotrigine an attractive treatment option for patients with primary generalized tonic-clonic seizures. LTG-IR has demonstrated efficacy in treatment-resistant idiopathic generalized epilepsies in both adults and children. Although there are still some questions regarding all possible applications of LTG-XR, as further research is being done, it is clear that LTG-XR may hold some advantages when compared with other anticonvulsants.

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          Most cited references 34

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          Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009.

          The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural-metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural-metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms.
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            A systematic review of the associations between dose regimens and medication compliance.

            Previous reviews of the literature on medication compliance have confirmed the inverse relationship between number of daily doses and rate of compliance. However, compliance in most of these studies was based on patient self-report, blood-level monitoring, prescription refills, or pill count data, none of which are as accurate as electronic monitoring (EM). In this paper, we review studies in which compliance was measured with an EM device to determine the associations between dose frequency and medication compliance. Articles included in this review were identified through literature searches of MEDLINE, PsychInfo, HealthStar, Health & Psychosocial Instruments, and the Cochrane Library using the search terms patient compliance, patient adherence, electronic monitoring, and MEMS (medication event monitoring systems). The review was limited to studies reporting compliance measured by EM devices, the most accurate compliance assessment method to date. Because EM was introduced only in 1986, the literature search was restricted to the years 1986 to 2000. In the identified studies, data were pooled to calculate mean compliance with once-daily, twice-daily, 3-times-daily, and 4-times-daily dosing regimens. Because of heterogeneity in definitions of compliance, 2 major categories of compliance rates were defined: dose-taking (taking the prescribed number of pills each day) and dose-timing (taking pills within the prescribed time frame). A total of 76 studies were identified. Mean dose-taking compliance was 71% +/- 17% (range, 34%-97%) and declined as the number of daily doses increased: 1 dose = 79% +/- 14%, 2 doses = 69% +/- 15%, 3 doses = 65% +/- 16%, 4 doses = 51% +/- 20% (P < 0.001 among dose schedules). Compliance was significantly higher for once-daily versus 3-times-daily (P = 0.008), once-daily versus 4-times-daily (P < 0.001), and twice-daily versus 4-times-daily regimens (P = 0.001); however, there were no significant differences in compliance between once-daily and twice-daily regimens or between twice-daily and 3-times-daily regimens. In the subset of 14 studies that reported dose-timing results, mean dose-timing compliance was 59% +/- 24%; more frequent dosing was associated with lower compliance rates. A review of studies that measured compliance using EM confirmed that the prescribed number of doses per day is inversely related to compliance. Simpler, less frequent dosing regimens resulted in better compliance across a variety of therapeutic classes.
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              Report of the ILAE classification core group.

               Jerome Engel (2006)
              A Core Group of the Task Force on Classification and Terminology has evaluated the lists of epileptic seizure types and epilepsy syndromes approved by the General Assembly in Buenos Aires in 2001, and considered possible alternative systems of classification. No new classification has as yet been proposed. Because the 1981 classification of epileptic seizure types, and the 1989 classification of epilepsy syndromes and epilepsies are generally accepted and workable, they will not be discarded unless, and until, clearly better classifications have been devised, although periodic modifications to the current classifications may be suggested. At this time, however, the Core Group has focused on establishing scientifically rigorous criteria for identification of specific epileptic seizure types and specific epilepsy syndromes as unique diagnostic entities, and is considering an evidence-based approach. The short-term goal is to present a list of seizure types and syndromes to the ILAE Executive Committee for approval as testable working hypotheses, subject to verification, falsification, and revision. This report represents completion of this work. If sufficient evidence subsequently becomes available to disprove any hypothesis, the seizure type or syndrome will be reevaluated and revised or discarded, with Executive Committee approval. The recognition of specific seizure types and syndromes, as well as any change in classification of seizure types and syndromes, therefore, will continue to be an ongoing dynamic process. A major purpose of this approach is to identify research necessary to clarify remaining issues of uncertainty, and to pave the way for new classifications.

                Author and article information

                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                18 November 2010
                : 4
                : 337-342
                Department of Neurology and Cincinnati Epilepsy Center, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA
                Author notes
                Correspondence: Jerzy P Szaflarski, Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson Street, Cincinnati, OH 45267-0525, USA, Tel +1 513 558 5440, Fax +1 513 558 4305, Email Jerzy.Szaflarski@
                © 2010 Steinbaugh and Szaflarski, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.


                Pharmacology & Pharmaceutical medicine

                lamotrigine, treatment, generalized seizures, ige, gtc


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