Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy

Binnie, C.D.; Debets, R. M. Chr.; Engelsman, Martijn; Meijer, J. W. A.; Meinardi, H.; Overweg, J.; Peck, A. W.; Wieringen, Astrid Van; Yuen, W. C.

doi:10.1016/0920-1211(89)90007-7

Cited by 163 publications

(52 citation statements)

References 7 publications

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“…The half-life of LTG is decreased by a factor of two during concomitant administration of CBZ and PHT ( I 1) and is increased by a factor of two or more during concomitant treatment with VPA (12). Therefore, the half-life of LTG can Serious adverse events reported rarely or infrequently with LTG during clinical trials and postmarketing surveillance include severe rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute kidney failure, and alterations in the blood profile (anemia, leukopenia, thrombocytopenia) (6,7,14,15).…”

Section: Ltgmentioning

confidence: 99%

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Overview of the Safety of Newer Antiepileptic Drugs

Shorvon

Stefan

1997

Epilepsia

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Summary: Standard antiepileptic drugs (AEDs) are associated with a wide variety of acute and chronic adverse events and with many interactions with each other and with nonAEDs that complicate patient management. The safety and interaction profiles of the newer AEDs have also been intensively studied. Safety data are available for six of the newer AEDs, lamotrigine (LTG), vigabatrin (VGB), gabapentin (GBP), tiagabine (TGB), felbamate (FBM), and topiramate (TPM). The potential for the most recently developed AEDs for producing rare idiosyncratic reactions cannot be ascertained until additional patient exposures have been reported from careful postmarketing surveillance.

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Section: Ltgmentioning

confidence: 99%

“…In these trials, 14% of TPM-treated patients and 3% of those who received placebo withdrew prematurely. For TPM-treated patients this occurred early in treatment, coincident with the rapid dose titration study phase ( 12).…”

Section: Tpmmentioning

confidence: 99%

Overview of the Safety of Newer Antiepileptic Drugs

Shorvon

Stefan

1997

Epilepsia

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“…Improvement rates ranged from 1 1 to 32% overall, and from 12 to 30% for recommended doses (p = 0.001) (21) U.S. GPT (21) Mut\uo ( 2 2 ) Matmo ( 2 2 ) 1 Binnie (23).…”

Section: Success and Improvement Ratesmentioning

confidence: 99%

New Antiepileptic Drugs: Comparison of Key Clinical Trials

et al. 1999

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Summary:Purpose: Data accrued from clinical trials of five new antiepileptic drugs (AEDs) are compared for efficacy in reducing seizures and self-reported adverse events as a basis of selection among new AEDs. Drawbacks to use of these data also are demonstrated.Methorh: A review of double-blind, placebo-controlled clinical trials of a new AED or placebo added to a standard AED provided data on reduction of complex partial seizures (CPSs). Success is 250% fewer CPSs with a new AED or placebo; Overall Improvement is the success rate with drug minus the success rate with placebo. Adverse events were tabulated from product-labeling lists of COSTART items (incidence, 2 5 % ) . The Summary Coinplaint score is the total number of reports of individual events for each AED.He,tults: Efficacy data demonstrate differences in Overall Improvement rates among five new AEDs and placebos (p = 0.001). However, rates of response to placebo also differed significantly among trials (p = 0.01). Adverse events predominantly affect central nervous system, psychiatric. and general body systems. However, patients in the placebo control groups did not consistently report adverse effects. Summary Coniplaint scores differ among the five new AEDs, but variability in use of COSTART terms nullifies comparisons.Conclu.sions: Comparisons of data for five new AEDs provide information for selection among treatments when ;I second drug is needed to iinprove control of CPSs. However, significant differences among the control groups and other problems make comparisons between trials problematic. The final choice should be based on the need of the individual patient for superior seizure control versus minimal adverse effects. likely efficacy and adverse effects. Selection of data from a single primary trial performed at the recommended dose might allow optimized comparisons among the new AEDs (6). A recent discussion of meta-analyses noted that summarization of data into a ~i n g l e odds ratio may not be the optimal approach for comparisons among clinical trials (73). Nonetheless, the meta-analysis provides valuable information to guide the planning of a future comparison among the new AEDs. A number of reviews described typical profiles of adverse effects. usually based on clinical experience, but without supporting data (9-1 1). Although Brodie's "Star System" (10) (a combination of efficacy, adverse events, and ease of use) is well founded based on clinical experience, it does not satisfy the need for numerically based comparisons from clinical trials. Most reports of clinical trials listed the incidence of common adverse effects based on patient self-report. These lists usually group problems based on an international dictionary of terms, COSTART, that provides a standardized format for the description of adverse events (12). A different approach was taken in the VA Cooperative Studies (1,2). Patients were asked direct questions and were examined for specific adverse effects by using Systemic and Neurotoxicity Rating Scales (13) to determine t...

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“…The efficacy of have been observed in adults receiving other AEDs [11]. Coadministration of hepatic enzyme-inducing lamotrigine as add-on therapy in adult patients with refractory partial epilepsy has previously been demonAEDs such as phenytoin, carbamazepine or phenobarbitone increase the elimination rate of lamotrigine [ 10, strated [3][4][5] and improvements in seizure control in children have also been reported [6,7].…”

mentioning

confidence: 99%

Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add‐on therapy in epileptic children

Vauzelle-Kervroëdan

Rey

Cieuta

et al. 1996

Brit J Clinical Pharma

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1 Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication. 2 This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively. 3 Thirty‐one children aged 6 months to 5 years were included and received a 2 mg kg−1 single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half‐lives (mean±s.d.) were: 7.7±1.8 h, 21.9±6.8 h, 44.7±10.2 h in the ‘inducer’, ‘other’ and ‘inhibitor’ groups respectively. 4 Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3 mg l−1. The mean minimum plasma concentration for the three groups was 2.54±1.28 mg l−1 at steady state. 5 Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.

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Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy

Cited by 163 publications

References 7 publications

Overview of the Safety of Newer Antiepileptic Drugs

Overview of the Safety of Newer Antiepileptic Drugs

New Antiepileptic Drugs: Comparison of Key Clinical Trials

Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add‐on therapy in epileptic children

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