Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug‐refractory epilepsy

Abstract

SUMMARYPurpose: To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load. Methods: Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED. Results: Of 809 patients enrolled, 709 had localizationrelated epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 ± 0.5 for patients on monotherapy to 2.5 ± 1, 3.7 ± 1.1, and 4.7 ± 1.1 for those on two, three, and ‡4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p < 0.0001). AEP scores did not differ between patients with monotherapy and patients with polytherapy (42.8 ± 11.7 vs. 42.6 ± 11.2), and there was no correlation between AEP scores and AED load (r = )0.05, p = 0.16). Conclusions: AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load, possibly as a result of physicians' intervention in individualizing treatment regimens. Taking into account the limitations of a cross-sectional survey, these findings are consistent with the hypothesis that AEs are determined more by individual susceptibility, type of AEDs used, and physicians' skills, than number of coprescribed AEDs and AED load.

Diagnosis and Management of Cerebral Venous Thrombosis

“…Mechanical manipulation of the thrombus with the guidewire increases the amount of clot that might be impacted by the thrombolytic agent, potentially reducing the amount of fibrinolytic agent used. 61,113,131,150,170,188,192,[195][196][197][198][199][200][201][202][203][204][205] In a retrospective multicenter study of CVT in the United States, 27 (15%) of 182 patients received endovascular thrombolysis. Ten patients were receiving concomitant anticoagulation therapy.…”

“…196,197,209 A few studies have reported the occurrence and characteristics of patients with seizures accompanying CVT. Among 91 patients, 1 study 218 reported that 32% presented with seizures and 2% developed them during hospitalization; only 9.5% developed late seizures, and seizures were not a predictor of prognosis at 1 year.…”

Epilepsia Refratária e Lamotrigina: Monitorização terapêutica e resposta clínica em pacientes ambulatoriais

“…A literatura apresenta divergências sobre esta questão (DECKERS et al, 2001;CANEVINI et al, 2010;SILLS, 2011;STEPHEN;. Frente a isso a avaliação da possível associação entre a PDD/DDD total ("drug load") e a presença de eventos adversos torna-se um parâmetro prático e útil para a tomada de decisão durante a definição do plano farmacoterapêutico.…”

Algorithms of mono- and polytherapy in clinical epileptology

“…В исследовании M. Canevini, были изучены взаимоот-ношения между выраженностью НЯ ПЭП, количеством назначаемых ПЭП и лекарственной нагрузкой ПЭП у па-циентов с фармакорезистентной эпилепсией [75]. Уста-новлено отсутствие значимых различий по выраженности НЯ при использовании режимов моно-и политерапии, количества используемых ПЭП (лекарственная нагрузка).…”

“…С помощью линейного мультивариантного регрессион-ного анализа авторами было показано, что число НЯ вследствие ПЭП значимо связано с женским полом (p=0,02) и высоким уровнем депрессии (p<0,0001). Не бы-ло выявлено влияния возраста, типа эпилептического синдрома, частоты приступов, применения режимов мо-но-или политерапии, доз применяемых ПЭП на выра-женность НЯ [75].…”