Antiepileptic drug treatment of generalized tonic–clonic seizures: An evaluation of regulatory data and five criteria for drug selection

Shorvon, Simon; Bermejo, Pedro Emilio; Gibbs, Ayana A.; Huberfeld, Gilles; Kälviäinen, Reetta

doi:10.1016/j.yebeh.2018.01.039

Cited by 23 publications

(16 citation statements)

References 87 publications

(111 reference statements)

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“…FBTCS are an adverse prognostic factor for seizure freedom after temporal lobe resection 6–8 . It remains unclear why temporal lobe seizures generalize in some patients but not in others 9,10 . It is crucial to identify factors that make some patients susceptible to FBTCS despite taking seizure‐suppressing medications.…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have suggested that impairments in specific brain regions support FBTCS, after finding disrupted structure and function in circuits mediated by thalamus and basal ganglia 6,12–18 . It has also been suggested that FBTCS have a different mechanism to primary generalized seizures, with more complex patient‐specific spread 10,19–23 . There is a need to investigate the full complexity of brain networks, 24 beyond the canonical thalamocortical pathways, 12 to delineate networks underlying FBTCS.…”

Section: Introductionmentioning

confidence: 99%

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Focal to bilateral tonic–clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy

et al. 2021

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Objective Our objective was to identify whether the whole‐brain structural network alterations in patients with temporal lobe epilepsy (TLE) and focal to bilateral tonic–clonic seizures (FBTCS) differ from alterations in patients without FBTCS. Methods We dichotomized a cohort of 83 drug‐resistant patients with TLE into those with and without FBTCS and compared each group to 29 healthy controls. For each subject, we used diffusion‐weighted magnetic resonance imaging to construct whole‐brain structural networks. First, we measured the extent of alterations by performing FBTCS‐negative (FBTCS−) versus control and FBTCS‐positive (FBTCS+) versus control comparisons, thereby delineating altered subnetworks of the whole‐brain structural network. Second, by standardizing each patient's networks using control networks, we measured the subject‐specific abnormality at every brain region in the network, thereby quantifying the spatial localization and the amount of abnormality in every patient. Results Both FBTCS+ and FBTCS− patient groups had altered subnetworks with reduced fractional anisotropy and increased mean diffusivity compared to controls. The altered subnetwork in FBTCS+ patients was more widespread than in FBTCS− patients (441 connections altered at t > 3, p < .001 in FBTCS+ compared to 21 connections altered at t > 3, p = .01 in FBTCS−). Significantly greater abnormalities—aggregated over the entire brain network as well as assessed at the resolution of individual brain areas—were present in FBTCS+ patients (p < .001, d = .82, 95% confidence interval = .32–1.3). In contrast, the fewer abnormalities present in FBTCS− patients were mainly localized to the temporal and frontal areas. Significance The whole‐brain structural network is altered to a greater and more widespread extent in patients with TLE and FBTCS. We suggest that these abnormal networks may serve as an underlying structural basis or consequence of the greater seizure spread observed in FBTCS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Focal to bilateral tonic–clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy

et al. 2021

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“…Lamotrigine is a novel antiepileptic drug of the phenyltriazine class which is used widely in epilepsy, simple and complex seizures, generalized tonic-clonic seizures, and bipolar disorder. 1,2 Its chemical name is 3, 5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine. 3 It acts by regeneration and modification of neurons function and Schwann cells by reducing glutamate release from nerve terminals in addition to a protective effect against cytotoxicity resulting from inhibition of mitochondrial respiratory complex I.…”

Section: Introductionmentioning

confidence: 99%

<p>Development, Characterization, and in-vivo Pharmacokinetic Study of Lamotrigine Solid Self-Nanoemulsifying Drug Delivery System</p>

Abdelmonem

Azer

Makky

et al. 2020

DDDT

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This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrigine (LMG) for enhancing its dissolution and oral bioavailability (BA). Methods: Nineteen liquid SNEDDS were prepared (R1-R19) using D-optimal design with different ratios of oil, surfactant (S), and cosurfactant (Cos). The formulations were characterized regarding robustness to dilution, droplet size, thermodynamic stability testing, selfemulsification time, in-vitro release in 0.1 N HCl and phosphate buffer (PB; pH 6.8). Design Expert ® 11 software was used to select the optimum formulations. Eight S-SNEDDS were prepared (S1-S8) using 2 3 factorial design, and characterized by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and scanning electron microscopy (SEM). The optimum formulation was chosen regarding in-vitro drug released in 0.1 N HCl and PB, compared to pure LMG and commercial tablet (Lamictal ®). The BA of LMG from the optimized S-SNEDDS formulation was evaluated in rabbits compared to pure LMG and Lamictal ®. Results: The optimized S-SNEDDS was S2, consisting of R9 adsorbed on Aeroperl ® 300 in a ratio of 1:1, with the best results regarding in-vitro drug released in 0.1 N HCl at 15 min (100%) compared to pure LMG (73.40%) and Lamictal ® (79.43%), and in-vitro drug released in PB at 45 min (100%) compared to pure LMG (30.46%) and Lamictal ® (92.08%). DSC, PXRD, and SEM indicated that LMG was molecularly dispersed within the solid nano-system. The BA of S2 was increased 2.03 and 1.605 folds compared to pure LMG, and Lamictal ® , respectively. Conclusion: S2 is a promising S-SNEDDS formulation. It can be a potential carrier for improving dissolution, and BA of LMG.

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“…For generalized-onset tonic-clonic seizures, valproate is recommended as first choice (except in women/girls of childbearing potential); lamotrigine and topiramate are valuable alternatives, however, lamotrigine can aggravate myoclonic seizures (e.g., in patients with Juvenile Myoclonic Epilepsy [JME]) ( Table 2) [21-23, 27, 31, 32]. Levetiracetam is effective as monotherapy for generalizedonset tonic-clonic seizures [27,31,32] but is currently not reimbursed for this seizure type in Belgium. Carbamazepine can also be considered as monotherapy for generalized-onset tonic-clonic seizures but is not effective against Information retrieved from each AED's summary of product characteristics (SmPC) and [25] b…”

Section: Generalized-onset Seizuresmentioning

confidence: 99%

Recommendations for the treatment of epilepsy in adult and pediatric patients in Belgium: 2020 update

et al. 2020

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To guide health care professionals in Belgium in selecting the appropriate antiepileptic drugs (AEDs) for their epilepsy patients, a group of Belgian epilepsy experts developed recommendations for AED treatment in adults and children (initial recommendations in 2008, updated in 2012). As new drugs have become available, others have been withdrawn, new indications have been approved and recommendations for pregnant women have changed, a new update was pertinent. A group of Belgian epilepsy experts (partly overlapping with the group in charge of the 2008/2012 recommendations) evaluated the most recent international guidelines and relevant literature for their applicability to the Belgian situation (registration status, reimbursement, clinical practice) and updated the recommendations for initial monotherapy in adults and children and add-on treatment in adults. Recommendations for add-on treatment in children were also included (not covered in the 2008/2012 publications). Like the 2008/2012 publications, the current update also covers other important aspects related to the management of epilepsy, including the importance of early referral in drug-resistant epilepsy, pharmacokinetic properties and tolerability of AEDs, comorbidities, specific considerations in elderly and pregnant patients, generic substitution and the rapidly evolving field of precision medicine.

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Antiepileptic drug treatment of generalized tonic–clonic seizures: An evaluation of regulatory data and five criteria for drug selection

Abstract: Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices.

Cited by 23 publications

References 87 publications

Focal to bilateral tonic–clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy

Focal to bilateral tonic–clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy

<p>Development, Characterization, and in-vivo Pharmacokinetic Study of Lamotrigine Solid Self-Nanoemulsifying Drug Delivery System</p>

Recommendations for the treatment of epilepsy in adult and pediatric patients in Belgium: 2020 update

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