Document Detail

Long-term control of epileptic drop attacks with the combination of valproate, lamotrigine, and a benzodiazepine: a 'proof of concept,' open label study.
MedLine Citation:
PMID:  21729037     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Long-term medical management of epileptic drop attacks is usually unsatisfactory and more effective antiepileptic drug (AED) regimens are needed. The present study aimed at providing proof of concept that previously refractory epileptic drop attacks could be significantly and safely controlled by the specific combination of valproate, lamotrigine, and a benzodiazepine.
METHODS: An open label trial providing class IV evidence of efficacy, including 32 patients with cryptogenic/symptomatic, generalized or multifocal epilepsies, and refractory drop attacks. Following baseline, the combination under study was introduced and patients followed for 12 months. Frequency of drop attacks was compared at 3-month intervals with that during baseline and correlated with clinical, electroencephalography (EEG), and imaging variables. A list of putative side effects was read to patients and caregivers at each visit.
KEY FINDINGS: Four patients were excluded, one due to a Stevens-Johnson syndrome (SJS). Median number of drop attacks decreased 96% between baseline and the fourth trimester of the study (from 50 to 2; p<0,001). Intention-to-treat (ITT) analysis showed that 15 patients (47%) had complete control, 7 (21%) had a 75% and 5 (15%) had a 50-74% reduction in the frequency of falls in the fourth trimester. Twenty-two patients (68%) had side effects, but except for the three excluded because of early rash, caregivers did not consider discontinuation. Mean final dose of valproate was 35.9 mg/kg/day and that of lamotrigine 4.9 mg/kg/day. Twenty patients used clobazam, eight nitrazepam, and the other four clonazepam as the elected benzodiazepine. Outcome did not correlate with clinical, EEG, and imaging variables.
SIGNIFICANCE: This open label study suggests that the combination of valproate, lamotrigine, and a benzodiazepine can markedly reduce the frequency of epileptic drop attacks in patients with generalized or multifocal epilepsies. Careful clinical monitoring for early signs of SJS is needed.
Vitor Hugo Machado; Andre Palmini; Fernanda Almeida Bastos; Rosana Rotert
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Publication Detail:
Type:  Clinical Trial; Journal Article     Date:  2011-04-19
Journal Detail:
Title:  Epilepsia     Volume:  52     ISSN:  1528-1167     ISO Abbreviation:  Epilepsia     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-06     Completed Date:  2011-09-13     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1303-10     Citation Subset:  IM    
Copyright Information:
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Severe Epilepsies Outpatient Clinic, Neurology Service, Avenida Ipiranga 6690, Porto Alegre, Brazil.
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MeSH Terms
Anticonvulsants / administration & dosage,  therapeutic use*
Benzodiazepines / administration & dosage,  therapeutic use*
Child, Preschool
Drug Therapy, Combination
Epilepsy / drug therapy*,  prevention & control
Middle Aged
Syncope / drug therapy,  prevention & control
Triazines / administration & dosage,  therapeutic use*
Valproic Acid / administration & dosage,  therapeutic use*
Young Adult
Reg. No./Substance:
0/Anticonvulsants; 0/Triazines; 12794-10-4/Benzodiazepines; 99-66-1/Valproic Acid; U3H27498KS/lamotrigine
Comment In:
Epilepsia. 2011 Nov;52(11):2139   [PMID:  22032792 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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