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Antiepileptic drug combinations-Have newer agents altered clinical outcomes?
MedLine Citation:
PMID:  21982026     Owner:  NLM     Status:  Publisher    
In 2000, 332 (20.5%) of 1617 patients registered with the Western Infirmary Epilepsy Unit required antiepileptic drug (AED) polytherapy to remain seizure-free for at least 1 year. The analysis was repeated 10 years later. Of 2379 seizure-free patients, 20.4% (n=486 - 254 women, 232 men, aged 18-95 years [median age 49 years]) were receiving combination therapy. Two AEDs were taken by 395 (81.3%) patients in 2010, and by 287 (86.4%) in 2000. Sodium valproate with lamotrigine was the commonest of 64 successful pairings. As a combination, mean daily doses of both AEDs were lower (n=96; sodium valproate 1200mg, lamotrigine 155mg) than when sodium valproate was taken with carbamazepine or levetiracetam (n=42; 1621mg; p<0.001), and lamotrigine was combined with topiramate or levetiracetam (n=33; 430mg; p<0.001), suggesting possible synergism. In 2010, a higher percentage of patients (n=85) remained seizure-free on 3 AEDs (17.5% in 2010, 12.7% in 2000) in 57 separate regimens. Only 0.9% (n=3) of patients in 2000, and 1.2% (n=6) in 2010 responded to 4 AEDs. Levetiracetam (n=109; 10.2%) and topiramate (n=81; 7.6%) were the newer agents most commonly represented in successful combinations. These data tend to imply that drug substitution rather than addition has largely led to these marginally improved results. In the last decade, when used as adjunctive therapies, newer agents appear not to have impacted substantially on the likelihood of producing seizure freedom. An alternative approach to AED development may be required to change this disappointing scenario.
Linda J Stephen; Murray Forsyth; Kevin Kelly; Martin J Brodie
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-5
Journal Detail:
Title:  Epilepsy research     Volume:  -     ISSN:  1872-6844     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8703089     Medline TA:  Epilepsy Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier B.V.
Epilepsy Unit, Division of Cardiovascular and Medical Sciences, Western Infirmary, Glasgow G11 6NT, Scotland, UK.
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