Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures

Beydoun, Ahmad; Fischer, James H.; Labar, Douglas; Harden, Cynthia L.; Cantrell, Deborah T. Combs; Uthman, Basim M.; Sackellares, J. Chris; Abou-Khalil, B.; Ramsay, R. Eugene; Hayes, Ailish M.; Greiner, Martha; Garofalo, Elizabeth; Pierce, Mark

doi:10.1212/wnl.49.3.746

Cited by 85 publications

(42 citation statements)

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“…There were two studies with class I evidence that evaluated the efficacy of gabapentin monotherapy for intractable partial seizure disorders. 38,39 One study 38 compared 300 to 3,600 mg/day. The study included intractable inpatients undergoing video-EEG monitoring who were off other AED.…”

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confidence: 99%

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Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

et al. 2004

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Abstract-Objective:To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. Methods: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. Results: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. Conclusions: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

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confidence: 99%

“…In the second study, 39 275 outpatients were randomized to one of three gabapentin monotherapy regimens at doses of 600, 1,200, and 2,400 mg/day, as part of a conversion from polytherapy to monotherapy gabapentin. Only 20% of patients completed the study.…”

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Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

et al. 2004

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“…Criticism includes ethical concerns about the use of a noneffective treatment arm in monotherapy and the fact that the new AED is tested for activity in a labile, withdrawal paradigm only. 23 Inpatient presurgical withdrawal designs may be suitable for PoC, but have been found to be obsolete for registration purposes. Concerns include the short duration time of a few days and the lack of generalizability of the results to a general partial epilepsy population, as well as ethical issues.…”

Section: Monotherapy Trialsmentioning

confidence: 99%

Clinical Development of Antiepileptic Drugs in Adults

Schmidt¹

2007

Neurotherapeutics

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Summary:Over the last two decades, ten so-called newer antiepileptic drugs (AEDs) have been approved around the world, the majority of which have found and maintained a place in the seizure-fighting armamentarium for the whole spectrum of epilepsies and epileptic syndromes; some of these drugs have features that are improved compared with the older drugs. Within that same time period, the process of clinical development of AEDs has also undergone changes and has become much more complex and costly. Efforts are underway to shift decision-making about the clinical viability of AED candidates to earlier development stages, using the concept of translational medicine. However, thus far all of the newer AEDs have undergone a standard development as an adjunct in the control of adult partial seizures; in some cases, development has been expanded to other seizure types and pediatric syndromes. Currently, the path to global approval for use in monotherapy is under review and is often debated with regulatory authorities. Clinical treatment guidelines consider randomized, blinded, well controlled studies as the premier level of evidence-based medicine; these studies originate mostly in confirmatory phases of the development program. However, with the rigid designs and criteria in regulatory driven trials, effectiveness in the clinical practice setting may not be sufficiently predicted by these studies, leading to frustrations from individual practitioners. Finally, additional safety issues regularly occur only after the postlaunch exposure to a broader population making necessary a continuing, and thorough, pharmacovigilance after the AED has come to market.

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“…Other outpatient withdrawal to monotherapy trials have compared LTG with VPA, and GBP, TPM, tiagabine (TGB), and OCBZ in a high-dose versus low-dose paradigm (23,25,(74)(75)(76)(77). Although we refer to these as pseudo-placebo trials, for the two VPA trials at least, the investigators intended that patients receive VPA at doses recommended by the package insert.…”

Section: What Is the Designmentioning

confidence: 99%

Foreward

French

2002

Epilepsia

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What is the clinical rationale for using AEDs in monotherapy? (Adapted from a talk by Jacqueline French, M.D.)Monotherapy has multiple advantages over polytherapy, including fewer side effects and drug-drug interactions, better patient compliance, less teratogenicity, and lower cost. Schmidt (1) demonstrated that when patients receiving standard polytherapy had one drug removed, 83% maintained the previous level of seizure control, 36% had fewer seizures, and 5% became seizure free. In addition, side effects decreased. Similarly, studies by Schmidt (2) and Mattson et al. (3) revealed that a second AED adds only marginal benefit. In their studies, only 11-13% of patients had a substantial decrease in seizures, and side effects increased.FDA monotherapy approval is particularly important for the newer AEDs, which have potential advantages of better tolerability, improved safety, less teratogenicity, and simpler pharmacokinetics, which cannot be realized when the new drugs are combined with older drugs that do not share these advantages. In addition, it is established practice to treat newly diagnosed patients with a single drug; therefore absence of a monotherapy license precludes anything but off-label use of new AEDs as initial therapy. Currently, prescribing these drugs as "offlabel" can present obstacles to insurance reimbursement and increase physician concern regarding legal liability.

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Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures

Cited by 85 publications

References 9 publications

Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

Clinical Development of Antiepileptic Drugs in Adults

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