Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.

Heller, A; Chesterman, Paul; Elwes, Robert; Crawford, Pamela; Chadwick, David; Johnson, Anthony L.; Reynolds, E. H.

doi:10.1136/jnnp.58.1.44

Cited by 240 publications

(132 citation statements)

References 16 publications

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“…The decrease in the prevalence of vigabatrin after 1997, also mentioned by Ackers et al, is probably the result of reports that vigabatrin can cause irreversible visual field defects [16]. The prevalence of phenobarbital is constant and higher than that of the new AEDs, even though this old AED has more severe side-effects than the new AEDs [17]. It has also been prescribed mostly to the youngest age category (0-4 years), likely due to its unique position of being recommended for the treatment of neonatal seizures Fig.…”

Section: Results Compared To Those Reported In the Literaturementioning

confidence: 88%

Antiepileptic drug utilization in children from 1997–2005—a study from the Netherlands

Vrie-Hoekstra

Vries

Berg

et al. 2008

Eur J Clin Pharmacol

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Objective To investigate the utilization of antiepileptic drugs (AEDs) in Dutch children and compare this with guidelines on the treatment of epilepsy in children.Method From the Dutch Interaction Database (IADB.nl) we selected children aged 0-19 years who received at least one prescription for an AED (ATC-code beginning with N03A) between 1997 and 2005. We calculated cumulative incidences and prevalences per 1000 children per year, stratified by age-category, sex and type of AED, and the total number of months each patient received at least one prescription of AEDs, and we counted the number of person-months and AEDs prescribed. For each AED, proportions of person-months were calculated for monoand combination therapy. Kaplan-Meier survival analysis was used to analyse the duration of AED use, stratified by sex. Results The overall prevalence of the prescription of AEDs to children was constant at approximately 4.0 per 1000 children during the years of the study. The overall cumulative incidence from 1997-2005 was 0.67 per 1000 children. When stratified by age category or sex, there were no relevant differences in incidence or prevalence. Valproic acid was the most frequently prescribed drug, followed by carbamazepine and lamotrigine. In 20.3% of all personmonths, patients received combination therapy; of these, 34.2% received combination therapy for 3 person-months or less. The older AEDs were prescribed more often as monotherapy than combination therapy, in contrast with the newer AEDs, for which the opposite was true. The 50% survival probability (= time period when 50% of children had stopped using AEDs) was around 2 years, with a significantly lower discontinuation of treatment for girls than boys (P = 0.04). Conclusion The overall cumulative incidence of AEDs was determined to be 0.67 per 1000 children, and the prevalence 4.0 per 1000 children. The most frequently prescribed drug is valproic acid, followed by carbamazepine and lamotrigine. The prescribing of AEDs seems to be in conformity with the overall recommendations of the guidelines on the treatment of epilepsy in children.

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Section: Results Compared To Those Reported In the Literaturementioning

confidence: 88%

Antiepileptic drug utilization in children from 1997–2005—a study from the Netherlands

Vrie-Hoekstra

Vries

Berg

et al. 2008

Eur J Clin Pharmacol

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“…We assumed that a majority of patients's epilepsies could be controlled with monotherapy (8)(9)(10), but there is insufficient evidence to guide a choice between the standard AEDs such as phenobarbitone (PB), diphenylhydantoin (DPH), carbamazepine (CBZ), and valproate (VPA) (2)(3)(4). It remains to be established whether specific drug combinations are more effective than others (5).…”

Section: Objectivesmentioning

confidence: 99%

“…The availability of AEDs and their cost are additional factors of concern for developing countries. The standard AEDs-PB, DPH, CBZ, and VPAhave been studied in several comparative monotherapy trials (2)(3)(4)27). As yet, we do not have clear evidence of a difference in efficacy among these AEDs.…”

Section: Choice Of Standard Aedsmentioning

confidence: 99%

“…all over the world due to several factors: (a) improved knowledge of the efficacy and tolerability of available standard AEDs (2)(3)(4); (b) acquisition of new information through observational studies and clinical trials, which allow more rational therapeutic decisions (5); (c) the introduction of new AEDs (6); and (d) the availability of alternate treatment options, such as surgery, for refractory partial epilepsy (7). Recent worldwide trends in the management of patients with epilepsy emphasize monotherapy over polytherapy (8-1 1).…”

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confidence: 99%

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Profile of Antiepileptic Pharmacotherapy in a Tertiary Referral Center in South India: A Pharmacoepidemiologic and Pharmacoeconomic Study

et al. 1999

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Summary:Purpose: To study the current pharmacotherapy practices of epilepsy and its economics in a developing country by correlating the epidemiology and economics of antiepileptic drug (AED) treatment in general epilepsy care and comprehensive epilepsy care.Methods: We compared the AED-use profiles, efficacy, and tolerability at entry and at last follow-up for 972 patients seen at a comprehensive epilepsy care program in South India from 1993 to 1995. The relative cost was expressed as the average percentage of the per capita gross national product (GNP/ capita) each individual spent for AED treatment.Results: At entry, 562 (57.8%) subjects were receiving polytherapy; at last follow-up, 743 (76.4%) patients were receiving monotherapy, an increase of 34.3% in the use of monotherapy. One or more adverse drug reactions were reported by 28.6% of patients at entry and by 19.8% at last follow-up. The proportion of patients who were seizure free increased from 29.0 to 44.8%. Carbamazepine (CBZ) was the most frequently used AED, followed by diphenylhydantoin (DPH), valproate (VPA), and phenobarbitone (PB). The relative cost (% GNPkapita) for standard AEDs were as follows: PB, 4.4%; DPH, 7.1%; CBZ, 16.8%; and VPA, 29.5%. The average annual cost of AED treatment per patient in U.S. dollars was $64.32 at entry and $47.73 at last follow-up. Reduction in polytherapy resulted in the net annual saving of $16,128 ($16.59 per patient, or 5.4% GNPhpita).Conclusions: The more frequent use of relatively expensive drugs like CBZ and VPA and the use of polytherapy-still quite prevalent in developing countries-has escalated the cost of AED therapy. Although in recent years AEDs have become more available in developing regions, primary and secondary care physicians have not been adequately educated about the current trends in the pharmacotherapy of epilepsy. Key Words: Antiepileptic drugs-Epilepsy syndromes-Pharmacotherapy-Pharmacoepidemiology-Pharmacoeconomics.An inquiry conducted between 1979 and 1983 by the Commission on Antiepileptic Drugs of the International League Against Epilepsy (ILAE) on the availability of antiepileptic drugs (AEDs) in 35 developing countries, including India, concluded that ' 'older and less efficacious compounds [such as phenobarbital (PB)] are the only AEDs available to most patients, whereas newer and more efficacious compounds are either not available or restricted to a very limited number of cases" (I). The Commission considered the data alarming and emphasized the need for more precise future studies.The approach to pharmacologic treatment of epileptic disorders has changed substantially in the past 2 decades Accepted July 17, 1998. Address correspondence and reprint requests to Dr. K . Radhakrishnan at Department of Neurology, Sree Chitra Tirunal Institue for Medical Sciences and Technology, Trivandrum-695 01 1, Kerala, India. all over the world due to several factors: (a) improved knowledge of the efficacy and tolerability of available standard AEDs (2-4); (b) acquisition of new information thro...

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“…This rate is higher by 10-20% for adults with tonic-clonic (grand-mal) seizure [5][6][7]. AEDs with delayed onset of action are less effective and favorable for patients because seizure reduction and/or cessation take longer, although patients have responded from such treatment [5,8]. Although the initial monotherapy successfully treats approximately half the patients with epilepsy, subsequent trials of monotherapy are less successful; overall, only 60-70% of patients become seizure free through monotherapy.…”

Section: Introductionmentioning

confidence: 99%

Evidence for Efficacy of Combination of Antiepileptic Drugs in Treatment of Epilepsy

2015

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Epilepsy is the tendency to have recurrent, unprovoked seizures. Although 70% of epileptic seizures can be controlled with monotherapy (treatment by single antiepileptic drug), a combination of two or more anti-epileptic drugs (AEDs) may be required to improve efficacy (seizure control) and tolerability. Polytherapy (treatment with two or more AEDs) can affect efficacies and side effects in additive, supra-additive (synergistic) or infra-additive fashion. The effect is considered supraadditive when the efficacy of the combination is greater than the sum of the individual drug efficacies, while it is considered infra-additive when the efficacy of the combination is less than the sum of the individual drug efficacies. Here, we have reviewed the available studies and evidences for the application of polytherapy in humans and animal models, to understand which combination of AEDs act as a synergistic polytherapy for epilepsy. We have searched the bibliographic databases MEDLINE and PubMed for studies conducted from 1950 to 2013 and have concluded that, although promising results from the experimental point of view support the combinations of topiramate separately with lamotrigine, gabapentin and felbamate, the most reliable evidence supports the use of valproate and lamotrigine, as this combination generates encouraging results in animal models. Though effectiveness of this combination is supported by human data, there is the possibility of increased side effects. The new drugs are all effective as add-on therapy; there is some evidence that at present, in clinical practice, levetiracetam and topiramate may be the most effective add-on therapies in partial and some generalized epilepsies.

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Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.

Cited by 240 publications

References 16 publications

Antiepileptic drug utilization in children from 1997–2005—a study from the Netherlands

Antiepileptic drug utilization in children from 1997–2005—a study from the Netherlands

Profile of Antiepileptic Pharmacotherapy in a Tertiary Referral Center in South India: A Pharmacoepidemiologic and Pharmacoeconomic Study

Evidence for Efficacy of Combination of Antiepileptic Drugs in Treatment of Epilepsy

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