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      The Risk Of Seizure-Related Hospitalization Among Older Adults On Levetiracetam Monotherapy: A Retrospective Comparative Cohort Study

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          Abstract

          Background

          Antiepileptic drug monotherapy is the mainstay of treatment for epilepsy; however, the efficacy of different antiepileptic drugs in reducing the incidence of seizure-related hospitalization among older adults, who are at higher risk of developing epilepsy compared to their younger counterparts, has not been examined.

          Purpose

          The objective of the present study was to compare the rate of seizure-related hospitalization among older adults on levetiracetam compared to different antiepileptic drugs (AEDs).

          Patients and methods

          This was a retrospective cohort study of older adults (≥60 years) in two tertiary care hospitals. Patients who are 60 years of age and older, have a confirmed diagnosis of epilepsy, and are taking a single and the same antiepileptic drug for at least 36 months were included. The patients were followed up for 24 months after 12 months of treatment with no incidence of seizure-related hospitalization via their health records. Multiple Poisson regression with robust error variance was used to estimate the relative risk of hospitalization for patients on levetiracetam compared to different antiepileptic drugs controlling for age, gender, number of prescription medications, dosage strengths, and Charlson Comorbidity Index (CCI) score.

          Results

          One hundred and thirty-six patients met the inclusion criteria and were included in the study. The recruited patients were on one of the following four antiepileptic drugs: carbamazepine (n=44), levetiracetam (n=39), phenytoin (n=31), and valproic acid (n=22). Patients on levetiracetam were more than twice as likely to be hospitalized due to seizures within the 24 months of follow-up compared to their counterparts on other AEDs (RR=2.76, 95% CI=1.16–6.53, P=0.021).

          Conclusion

          This study suggests that older adults on old generation AEDs such as phenytoin, carbamazepine, and valproic acid appear to have a lower risk of seizure-related hospitalization compared to their counterparts on levetiracetam.

          Most cited references18

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          The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country.

          To determine the prevalence of epilepsy in a defined adult population and identify the frequency and principal features of pharmacoresistant epilepsy. From a population over 15 years of age residing in a medium-sized French city, all patients with epilepsy on June 30, 1995 were identified from multiple sources. Pharmacoresistance was defined as failure to control epilepsy by at least two first-line antiepileptic drugs, with a seizure frequency of at least one per month for 18 months. Collected data were examined by experts in epileptology, and responding patients were reexamined using a standardized diagnostic questionnaire. ILAE definitions and classifications were used. The age-adjusted prevalence of active epilepsy was 5.4 per 1,000 (95% CI: 4.7-6.0) and was higher for males (7.8) than for females (5.2). For epilepsy in remission under treatment, this rate was 0.7 per 1,000 (95% CI: 0.5-0.95). Age-specific prevalence was highest in age groups 25-49 years and declined in the oldest age groups. Localization-related seizures represented 61.1% of cases and generalized seizures 30.9%. The proportion of noncontrolled epilepsy (seizure-frequency at least one per month for 18 months) was 15.6%, corresponding to a prevalence of 0.94 per 1,000. In this group, the mean age at onset was lower (p = 0.0007) and localization-related epilepsy more frequent (p = 0.01). The findings support previous epidemiological estimates of the prevalence of epilepsy in developed countries. For approximately one patient in eight, epilepsy was not adequately controlled.
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            Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy.

            We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled-release carbamazepine as first treatment in newly diagnosed epilepsy. Adults with > or =2 partial or generalized tonic-clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled-release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double-blind, noninferiority, parallel-group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6-month seizure freedom) continued on treatment for a further 6-month maintenance period. At per-protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled-release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI -7.8% to 8.2%) for > or =6 months (1 year). Of all patients achieving 6-month (1-year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine. Levetiracetam and controlled-release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double-blind setting previously uncontrolled observations that most people with epilepsy will respond to their first-ever antiepileptic drug at low dosage.
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              Phenobarbital for the treatment of epilepsy in the 21st century: a critical review.

              Phenobarbital (PB) is the most widely used antiepileptic drug (AED) in the developing world and remains a popular choice in many industrialized countries. Meta-analyses of randomized controlled trials suggest that few differences in efficacy exist between PB and other established AEDs, but its possible deleterious cognitive and behavioral side effects remain a concern in the developed world. In contrast, high degrees of efficacy and tolerability in everyday clinical use have been demonstrated consistently in observational studies in developing countries. We propose that a pragmatic, comprehensive outcomes program be carried out, perhaps under the aegis of the Global Campaign Against Epilepsy, to optimize the conditions of the use of PB, so that more people around the world can benefit from this cost-effective medication and live more fulfilling lives. Copyright 2004 International League Against Epilepsy
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                NDT
                neurodist
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                24 September 2019
                2019
                : 15
                : 2781-2788
                Affiliations
                [1 ]Department of Pharmacy, King Saud University Medical City , Riyadh, Saudi Arabia
                [2 ]Department of Clinical Pharmacy, College of Pharmacy, King Saud University , Riyadh, Saudi Arabia
                [3 ]Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University , Riyadh, Saudi Arabia
                [4 ]Department of Medicine, Neurology Division, College of Medicine, King Saud University , Riyadh, Saudi Arabia
                [5 ]Department of Pharmaceutical Care, King Faisal Specialist Hospital and Research Center , Riyadh, Saudi Arabia
                [6 ]Department of Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia
                [7 ]Department of Neurosciences, King Faisal Specialist Hospital and Research Centre , Riyadh, Kingdom of Saudi Arabia
                Author notes
                Correspondence: Yazed AlRuthia Department of Clinical Pharmacy, College of Pharmacy, King Saud University , Riyadh, Saudi ArabiaTel +996 11 4677483Fax +966 11 4677480 Email yazeed@ksu.edu.sa
                Author information
                http://orcid.org/0000-0002-0029-5924
                http://orcid.org/0000-0001-6041-6241
                http://orcid.org/0000-0002-4196-3239
                Article
                221403
                10.2147/NDT.S221403
                6765395
                5daea0e1-6c3a-47fc-8940-07db401908cf
                © 2019 Alzahrani et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 30 June 2019
                : 09 September 2019
                Page count
                Figures: 2, Tables: 2, References: 36, Pages: 8
                Categories
                Original Research

                Neurology
                seizures,hospitalization,levetiracetam,carbamazepine,phenytoin,valproic acid
                Neurology
                seizures, hospitalization, levetiracetam, carbamazepine, phenytoin, valproic acid

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